| 1. |
- Christenson, Brith, et al.
(författare)
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Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity
- 2008
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Ingår i: Virology Journal. - 1743-422X. ; 5, s. 52-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The present prospective study was conducted from 2003-2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area.The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS) even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. RESULTS: In 2003, the total study population was 41,059, of which 12,907 (31%) received influenza vaccine of these, 4,447 (11%) were administered the pneumococcal vaccine. In 2004, 14,799 (34%) individuals received the influenza vaccine and 8,843 (21%) the pneumococcal vaccine and in 2005 16,926 (39%) individuals were given the influenza vaccine and 12,340 (28%) the pneumococcal vaccine.Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine). Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council.During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age). For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75-84-year old age group and in all age-groups during the influenza season 2005. CONCLUSION: The present study confirmed the additive effect of the two vaccines in the elderly, which was associated with a reduced risk in hospitalisation and a reduction in mean LOHS in seasons with low influenza activity.
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| 2. |
- Cunningham, Anthony L., et al.
(författare)
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Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:11, s. 1750-1760
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Tidskriftsartikel (refereegranskat)abstract
- Background. The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01(B) Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods. Participants (ZOE-50: >= 50; ZOE-70: >= 70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing >= 2 of 4 activation markers assessed (CD4(2+)) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results. After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD4(2+) T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained >= 5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.
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| 3. |
- Fohlman, Jan, et al.
(författare)
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Antiviral treatment with WIN 54954 reduces mortality in murine Coxsackie virus B3 myocarditis
- 1996
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 94:9, s. 2254-2259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis is some cases of dilated cardiomyopathy, a clinical entity with a poor survival without heart transplantation. METHODS AND RESULTS: In vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhibitory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in complete protection from enteroviral mortality (P < .01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No difference was found in the expression of surface lymphocyte subset markers. At 3 weeks, macrophages seemed to dominate the inflammatory reaction, regardless of treatment. There was no difference in CBV3 antibody titers, indicating that WIN 54 954 does not interfere with the development of protective immunity. Complement factors C3 and B were synthesized at a higher level during infection and correlated well with the degree of inflammatory reaction. CONCLUSIONS: The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on survival in CBV-induced myocarditis in the A/J mouse if treatment is started early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus replication in affected organs that does not interfere with cellular or humoral immunity.
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| 4. |
- Frisk, Per, et al.
(författare)
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Skin infection caused by Mycobacterium szulgai after allogenic bone marrow transplantation
- 2003
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 31:6, s. 511-513
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Tidskriftsartikel (refereegranskat)abstract
- Infections are responsible for a large part of the morbidity and mortality after BMT because of the sustained impairment of host defenses. We report a case of cutaneous infection caused by Mycobacterium szulgai in a boy who underwent BMT with marrow from a matched unrelated donor.
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| 5. |
- Hammarström, Helena, et al.
(författare)
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Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies
- 2023
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Ingår i: Clinical Infectious Diseases. - : University of Chicago Press. - 1058-4838 .- 1537-6591. ; 76:3, s. e1252-e1260
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies.METHODS: This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.RESULTS: Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30.CONCLUSION: In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.
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| 6. |
- Hammarström, Viera, et al.
(författare)
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Serum immunoglobulin levels in relation to levels of specific antibodies in allogeneic and autologous bone marrow transplant recipients
- 2000
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 69:8, s. 1582-1586
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to investigate the correlation of total levels of immunoglobulins to levels of specific antibodies after allogeneic and autologous bone marrow transplantation. Autologous transplant patients had normal levels of IgA and IgG antibodies already at 6 months after transplantation. In allogeneic transplanted patients without chronic graft versus host disease the immunological recovery was slower. The IgA and IgG levels were at the limit for deficiency at 6 months after transplantation. In allogeneic transplant patients with chronic chronic graft versus host disease the immunological recovery was delayed further. The total IgG levels were low at 12 months after transplantation and the IgG subclass pattern did not normalize until 24 months after transplantation. IgA levels remained low at 24 months after transplantation in all allogeneic transplanted patients with chronic chronic graft versus host disease. Protective levels of specific antibodies against tetanus and pneumococci decreased during the first year after transplantation regardless of the total immunoglobulin levels, regardless of the donors immunity. Pneumococcal antibodies decreased only in allogeneic transplanted patients, although autologous transplant patients retained pretransplant immunity against pneumococci. There was no difference in levels of specific antibodies between patients with and without chronic chronic graft versus host disease at 12 months after transplantation. There was no correlation between total immunoglobulin levels to levels of specific antibodies against tetanus and pneumococci after transplantation in our study. Taken together, normalized immunoglobulin levels do not predict normalization of levels of specific antibodies against tetanus and pneumococci after transplantation.
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| 7. |
- Hammarström, Viera, et al.
(författare)
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Tetanus immunity in autologous bone marrow and blood stem cell transplant recipients
- 1998
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 22:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to assess long-term immunity and reimmunization responses against tetanus toxoid in recipients of autologous stem cell grafts and to compare immune status in patients who underwent ABMT or autologous blood stem cell transplantation (APBSCT). Ninety patients were included in the study; 52 had received ABMT and 38 APBSCT. Thirty of 52 ABMT patients (58%) and 25 of 38 APBSCT patients (66%) had protective antibody levels against tetanus before transplantation (P = NS). The rate of seropositivity had decreased at 1 year after transplantation; 15 of 52 (29%) ABMT patients and 18 of 38 (47%) APBSCT patients (P = NS) were still positive after 1 year. There were no cases of spontaneous recovery in seronegative patients. Most patients were reimmunized with three doses of tetanus toxoid given at 12, 13, 14 and or 18 months after transplantation. All immunized patients had protective immunity against tetanus at 1 year after vaccination. These results suggest that humoral immunity is defective both after ABMT and after APBSCT and in both cases the loss of immunity seems to be similar. Reimmunization of patients who have undergone ABMT or APBSCT is necessary to obtain protective immunity against tetanus.
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| 8. |
- Hammarström, Viera, et al.
(författare)
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Tetanus immunity in patients with hematological malignancies
- 1998
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 6:5, s. 469-472
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.
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| 9. |
- Hastie, Andrew, et al.
(författare)
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Immunogenicity of the adjuvanted recombinant zoster vaccine : persistence and anamnestic response to additional doses administered 10 years after primary vaccination.
- 2020
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 224:12, s. 2025-2034
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years (Y) of age (YOA). We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule by following-up adults vaccinated at ≥60 YOA and by modeling, and (2) immunogenicity of 2 additional doses administered 10Y post-initial vaccination.METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10Y post-initial vaccination, and modeled through 20Y using a Piecewise, Power law and Fraser model. Immunogenicity and safety of 2 additional RZV doses were also evaluated (NCT02735915).RESULTS: Seventy adults were enrolled. Ten years post-initial vaccination, humoral and CMI responses were ~6-fold and ~3.5-fold above pre-initial vaccination levels, respectively. Predicted immune persistence through 20Y post-initial vaccination was similar across the 3 models. Sixty-two participants (82.6±4.4 YOA) received at least 1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose.CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10Y after the initial 2-dose course.
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| 10. |
- Joona, Therse Björkin, et al.
(författare)
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Influenza vaccination in breast cancer patients during subcutaneous trastuzumab in adjuvant setting
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 184:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting.Methods: A prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured.Results: Twenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%,pvalue = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination.Conclusion: Breast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.
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| 11. |
- Karawajczyk, G., et al.
(författare)
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The differential release of eosinophil granule proteins : Studies on patients with acute bacterial and viral infections
- 1995
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Ingår i: Clinical and Experimental Allergy. - 0954-7894 .- 1365-2222. ; 25:8, s. 713-719
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Earlier in vitro studies have suggested that the eosinophil may release its granule proteins selectively depending on the stimulus to which the cell is exposed. OBJECTIVE: The object of the present study was to study the question of selective release in vivo by means of serum measurements of the two eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in acute infections. METHODS: Fourty-six subjects with acute infections were studied before treatment, 20 with bacterial infections and 26 with viral infections. Serum ECP, EPO and MPO were measured by specific RIA. RESULTS: In acute bacterial infections ECP, but not EPO, was significantly raised in serum (P < 0.0001) compared with non-infected healthy subjects. In acute bacterial infections ECP was significantly correlated to the levels of the neutrophil marker myeloperoxidase (MPO) (rs = 0.96, P < 0.0001) but not to EPO. In acute viral infections neither ECP nor EPO were on average raised. However, almost 20% the patients had elevated levels of bot proteins. In the viral infections the serum-levels of ECP and EPO were correlated (rs = 0.63, P < 0.001), but no correlation was found with MPO. CONCLUSION: It is concluded that eosinophils are activated during acute bacterial infections and that this activation results in the preferential mobilisation of ECP. The simultaneous assay of the two eosinophil proteins, ECP and EPO, may give new insight into the role of the eosinophil in disease.
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| 12. |
- Karawajczyk, Malgorzata, et al.
(författare)
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High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19
- 2021
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Ingår i: Therapeutic advances in infectious disease. - : Sage Publications. - 2049-9361 .- 2049-937X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU).Methods: The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors.Results: Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96).Conclusion: Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.
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| 13. |
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| 14. |
- Kinch, Amelie, 1973-, et al.
(författare)
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Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT
- 2018
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 59:5, s. 1172-1179
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Tidskriftsartikel (refereegranskat)abstract
- We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.
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| 15. |
- Kinch, Amelie, 1973-, et al.
(författare)
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Prior antithymocyte globulin therapy and survival in post-transplant lymphoproliferative disorders
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:6, s. 771-778
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment with antithymocyte globulin (ATG) is a well-recognized risk factor for the development of post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, but it is unknown how its use affects overall survival after PTLD. Methods: A total of 114 patients with PTLD and available data on immunosuppressive regimen were included from a nation-wide case series of solid organ transplant recipients in Sweden. Prior use of ATG was correlated to clinical features, PTLD subtype, and survival. Results: A total of 47 (41%) patients had received ATG prior to the diagnosis of PTLD. The ATG-treated patients were more likely to be recipients of hearts or lungs, and less likely of kidneys (p < 0.01). They had experienced more acute rejections (p = 0.02). The PTLDs arose earlier, median 2.0 vs. 6.6 years post-transplant (p = 0.002) and were more often situated in the allograft (32% vs. 7%, p < 0.001) in patients with prior ATG vs. no ATG treatment. The PTLDs in the ATG group were more often Epstein-Barr virus-positive (80% vs. 40%, p < 0.001). There were more polymorphic PTLDs (17% vs. 1.5%, p = 0.004) and less T-cell PTLDs (4% vs. 19%, p = 0.02) in the ATG group than in the no ATG group. Diffuse large B-cell lymphoma was equally common in patients with and without prior ATG therapy, but the non-germinal center subtype was more frequent in the ATG group (p = 0.001). In an adjusted Cox proportional hazards regression model, prior ATG treatment and better performance status were associated with superior overall survival, whereas older age, T-cell subtype of PTLD, presence of B symptoms, and elevated lactate dehydrogenase were associated with inferior overall survival. Patients receiving ATG solely as rejection therapy had superior overall survival compared with those receiving ATG as induction therapy or both (p = 0.03). Conclusions: ATG therapy, especially rejection therapy, prior to PTLD development is an independent prognostic factor for superior overall survival after PTLD diagnosis.
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| 16. |
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| 17. |
- Lignell, Anders, et al.
(författare)
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Low utilisation of unactivated protein C in a patient with meningococcal septic shock and disseminated intravascular coagulation
- 2003
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 47:7, s. 897-900
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Activated protein C has recently been shown in a multicentre trial to significantly reduce mortality in patients with septic shock. There are also some case reports and minor studies demonstrating promising results with the unactivated form of protein C. However, in children with severe meningococcal infection, skin biopsies have demonstrated low expression of endothelial thrombomodulin and protein C receptors, suggesting low protein C activation capacity in severe meningococcal sepsis. METHODS: A patient with meningococcal septic shock was treated with two doses of the unactivated form of protein C, the first during intense activation of the coagulation system and the second during a phase of low grade or no activation. Repeated plasma samples were analysed for protein C concentration, which made it possible to compare pharmacokinetics and half-lives of the two administrations. A shorter half-life during intense coagulation was expected if there was an activation and consumption of the protein C administered. RESULTS: The calculated half-lives of protein C during intense and low grade activation were 32 h and 19 h, respectively, a magnitude similar to that reported in protein C-deficient patients without infection. CONCLUSION: The result indicates that whole body utilisation of the unactivated protein C was low. Endothelial impairment of protein C activation does not seem to be restricted to the skin vessels only.
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| 18. |
- Ljunghill Hedberg, Anna, 1972-
(författare)
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Impact of the inflammatory response on specific immunity in neurosurgical patients
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vaccination with a T-cell-dependent pneumococcal conjugate vaccine (PCV) followed by a T-cell-independent pneumococcal polysaccharide vaccine (PPSV) is recommended after basilar skull fracture to reduce the risk of meningitis. The optimal time frame for vaccination has not yet been established and varies widely in practice. Because the risk of meningitis is at its peak shortly after the trauma incident, early vaccination might be more desirable. After trauma and central nervous system (CNS) injury, T-cell defects leading to trauma and CNS injury-induced immune deficiency syndromes may affect the vaccine response. In light of the above information, the overall aim of this thesis was to investigate the impact of neurotrauma and neurosurgery on the response to T-cell-dependent and T-cell-independent vaccines.In Paper I, we compared the antibody response to a T-cell-dependent conjugate vaccine in patients vaccinated within 10 days after neurotrauma or neurosurgery with those vaccinated after >3 weeks. To avoid interference with pneumococcal vaccination, a conjugate vaccine against Haemophilus influenzae type b (Hib) was chosen for the study. The majority of the patients responded to the vaccination, although the number of responders was significantly lower in patients vaccinated early.In Paper II, we investigated the antibody response to the T-cell-independent vaccine PPSV in patients vaccinated within 10 days after neurotrauma or neurosurgery and in patients vaccinated after >3 weeks. Patients vaccinated early responded similarly to those vaccinated after the acute period, indicating that PPSV can be administered early after neurotrauma or neurosurgery.In Paper III, we compared the response to Hib vaccine with the response to PPSV. We also examined whether individual clinical or immunological parameters might predict the response to T-cell-dependent vaccine and thereby help identify non-responders before vaccination. No correlation between Hib vaccine and PPSV responses was found, indicating that B-cell function is not similarly depressed as T-cell function. It was not possible to predict the T-cell-dependent vaccine response by standardized grading of the trauma or by parameters reflecting the innate immune response.In Paper IV, we found a significant reduction in the ex vivo CD4+ T-lymphocyte response to PCV in patients after neurotrauma or neurosurgery as compared with healthy controls.Our results suggest that PPSV might be a viable alternative to T-cell-dependent PCV in early vaccination after neurotrauma.
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| 19. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults
- 2015
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 70:6, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. Methods: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. Results: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log(10) anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 mu g/ml, respectively. Conclusions: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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| 20. |
- Ljunghill Hedberg, Anna, et al.
(författare)
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Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma : Can the response be predicted?
- 2022
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Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis Group. - 2164-5515 .- 2164-554X. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: After trauma and central nervous system (CNS) injury, trauma-induced immune deficiency syndrome (TIDS) and CNS injury-induced immune deficiency syndrome (CIDS) may negatively affect responses to T-cell-dependent vaccines, such as pneumococcal conjugate vaccine (PCV) recommended after basilar fracture. This study (NCT02806284) aimed to investigate whether there after neurotrauma is a correlation between T-cell-dependent and independent vaccine responses and, thus, if B-cell activity is similarly depressed and whether the T-cell-dependent response is possible to predict.Method: Adult patients with basilar fracture (n = 33) and those undergoing pituitary gland surgery (n = 23) were within 10 days vaccinated with a T-cell-dependent vaccine against Haemophilus influenzae type b (Hib) and a T-cell-independent pneumococcal polysaccharide vaccine (PPSV). Samples reflecting the systemic inflammatory response and pre- and post-vaccination antibody levels after 3–6 weeks against Hib and PPSV were collected and determined by enzyme immunoassays.Results: High and significant correlations were detected in the responses to different pneumococcal serotypes, but none between the Hib and PPSV responses. No differences in trauma scores, C-reactive protein, IL-6, IL-10, pentraxin 3, fractalkine or calprotectin plasma concentrations or in ex vivo TNF-α, IL-6 or IL-10 responses to endotoxin were found between Hib vaccination responders and non-responders.Conclusions: There was no correlation between the pneumococcal responses and that to Hib, indicating that B-cell function is not similarly depressed as T-cell function. Grading of the trauma or parameters reflecting the innate immune response could not predict the T-cell-dependent vaccine response. There is a need of further studies evaluating the vaccine response after neurotrauma.
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| 21. |
- Ljungman, P., et al.
(författare)
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Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients
- 1996
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:3, s. 565-568
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Tidskriftsartikel (refereegranskat)abstract
- Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for toxicity. One patient did not fulfill the inclusion criteria of two consecutively positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of 15 patients were evaluable for development of CMV disease. None of the patients developed CMV disease and all 14 assessable patients had a negative CMV isolation at the end of therapy. None of the 15 patients had to discontinue therapy due to toxicity. Six patients reported mild gastrointestinal disturbances, three patients headaches, and three patients mild urethritis or hemorrhagic cystitis. Serum-electrolyte disturbances were common including abnormal magnesium, potassium and calcium levels. Two patients developed mild serum-creatinine increases requiring adjustment of the foscarnet dosage according to protocol. We conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be safe and effective in preventing CMV disease in allogeneic BMT recipients. A study comparing foscarnet and ganciclovir is indicated.
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| 22. |
- Ljungman, P., et al.
(författare)
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Respiratory virus infections after stem cell transplantation : a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation
- 2001
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 28:5, s. 479-484
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Tidskriftsartikel (refereegranskat)abstract
- Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.
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| 23. |
- López-Fauqued, M., et al.
(författare)
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Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
- 2019
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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| 24. |
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| 25. |
- Melin, Jan, et al.
(författare)
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Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients
- 2021
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Ingår i: BMC Immunology. - : BioMed Central (BMC). - 1471-2172. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. Methods In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7-15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. Results Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. Conclusions Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.
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| 26. |
- Norrby-Teglund, Anna, et al.
(författare)
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Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections
- 1995
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 27:2, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.
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| 27. |
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| 28. |
- Pauksen, Karlis, et al.
(författare)
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Granulocyte-macrophage colony-stimulating factor as immunomodulating factor together with influenza vaccination in stem cell transplant patients
- 2000
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 30:2, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation (SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P<.05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P<.05) and B (P<.01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.
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| 29. |
- Pauksen, Karlis, et al.
(författare)
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Influence of the specific T cell response on seroconversion after measles vaccination in autologous bone marrow transplant patients
- 1996
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:5, s. 969-973
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Tidskriftsartikel (refereegranskat)abstract
- Six patients who were seronegative to measles after autologous bone marrow transplantation (ABMT) were vaccinated with a live attenuated measles vaccine. The specific T helper cell response was studied by measuring lymphocyte proliferation induced by measles antigen and B cell response by measles specific IgG by ELISA. Blood samples were drawn before, at 1-3 months, and at 1 year after vaccination. It was found that a pre-existing T cell response correlated with an impaired B cell response 1 year after vaccination (r = 0.83, P = 0.04), whereas no correlation was found between IgG titers before vaccination and IgG titer increase, or T cell response after vaccination. Furthermore, there was a transient negative correlation between the T cell response at 1-3 months after vaccination and the T cell response before vaccination (r = -0.90, P = 0.04) that became positive at 1 year after vaccination (r = 0.90, P = 0.02). In conclusion, in patients seronegative to measles who were revaccinated with measles vaccine after ABMT, a pre-existing T cell response correlated with an impaired B cell response, while pre-existing low-level IgG antibodies had no significant influence on the IgG titer rise. A sustained T cell response to measles antigen before vaccination may thus be one possible explanation for measles vaccine failure in ABMT patients.
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| 30. |
- Pauksen, Karlis, et al.
(författare)
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Specific T and B cell immunity to measles after allogeneic and autologous bone marrow transplantation
- 1995
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 16:6, s. 807-813
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocyte stimulation with measles virus antigen (MLY) and ELISA for measles IgG antibodies were performed on 60 patients after allogeneic bone marrow transplantation (BMT), and on 59 patients after autologous bone marrow transplantation (ABMT). The T cell response was significantly higher in the 75 measles seropositive patients than in the 29 seronegative patients (P < 0.001), but not significantly different from the MLY in the 15 patients with uncertain serologic reactivity. When the patient group was divided according to type of transplant, the T cell response to measles was also significantly higher in seropositive patients than in seronegative patients after both ABMT (P < 0.001) and after BMT (P < 0.05). Twenty-three seronegative children who were measles vaccinated after BMT had a significantly higher T cell response to measles (7100 c.p.m.) than 17 seronegative non-vaccinated children (100 c.p.m.; P < 0.01). No significant difference was seen in the T cell response in 12 seronegative children vaccinated after ABMT (2500 c.p.m.) compared to seven children not vaccinated (2800 c.p.m.; NS). Seroconversion after vaccination was more frequent in children after BMT (20/23; 87%) compared to ABMT (5/12; 42%; P < 0.05) but no significant difference was found in the T cell response. Therefore, most patients who lost IgG antibodies to measles after bone marrow transplantation also lost their T cell response to measles. A T cell response to measles developed in most patients who seroconverted after vaccination. Failure to develop antibodies to measles in ABMT patients after revaccination may depend on a persisting T cell immunity.
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| 31. |
- Pauksen, Karlis, et al.
(författare)
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Subsets of T-cells and in vitro cytokine production after measles and varicellae-zoster virus antigen stimulation in allogeneic BMT patients
- 1999
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 31:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to analyse differences in T-cell proliferation induced by a latent virus, varicellae-zoster virus (VZV) and a non-latent virus, measles virus, in patients after allogeneic bone marrow transplantation (BMT). The lymphoproliferative response to measles antigen, VZV-antigen (VZV-ag), and phytohemagglutinin (PHA) was measured by 3H-thymidine incorporation, and interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) analyses in supernatants after in vitro stimulation of peripheral blood mononuclear cells (PBMC) from 22 patients and 18 healthy controls. The cytokine levels were correlated with T-cell subsets by FACS analyses. At the antigen concentrations used, VZV-ag induced higher levels of IFN-gamma (p < 0.05) than did the measles antigen, whereas the levels of IL-10 were similar. Patients without a cell mediated immune (CMI) response to VZV-ag or measles antigen had lower CD4+ T-cell counts than did controls (p < 0.01 in both cases) and lower IFN-gamma production after non-specific PHA stimulation (p <0.01). The IFN-gamma and IL-10 levels after measles antigen stimulation correlated with the number of CD4+ T-cells (p < 0.01 and p < 0.05, respectively), and after VZV-ag mainly to the number of CD8+ T-cells (p < 0.01 and p < 0.05, respectively). These results suggest that there is a difference in the types of T-cells that respond to VZV-ag and measles antigen stimulation, respectively. The impaired CMI response to viral antigens seen in many patients may be explained both by a low number of CD4+ T-cells and by a cell dysfunction.
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| 32. |
- Pauksen, Karlis, et al.
(författare)
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Th1 and Th2 cytokine response after measles antigen stimulation in vitro in bone marrow transplant patients : response to measles vaccination
- 1997
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 20:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- In seronegative autologous bone marrow transplanted (ABMT) patients, a sustained cell-mediated immunity (CMI) has been shown to impair the antibody response after measles vaccination. To investigate if this might be caused by a preferential Th1 cytokine response, interferon (IFN)-gamma and interleukin (IL)-10 production of peripheral blood mononuclear cells (PBMC) was analyzed after measles antigen (M-ag) stimulation in vitro. The non-specific immune response was measured by IFN-alpha, and IL-12 analyses. Fifty non-vaccinated patients following ABMT or allogeneic bone marrow transplantation (BMT) were included. IFN-gamma production was significantly higher in patients with a retained CMI to measles than in patients without (2.3 vs 0.8 IU/ml; P = 0.01). Only a non-significant tendency was seen in IL-10 production (48.6 vs 26.7 pg/ml; NS), whereas no difference was found in IFN-alpha or IL-12 production. A positive correlation between IFN-gamma and IL-10 production was found (r(s) = 0.49; P < 0.001). After vaccination of 14 ABMT children, there was an increase in PBMC IFN-gamma production in vitro (2.5 vs <0.1 IU/ml; P < 0.05), whereas no changes were seen in the IL-10, IFN-alpha, or antibody levels. These results suggest that both Th1 and Th2 cytokine production are increased by M-ag stimulation in patients with a retained CMI to measles, but the Th1 response seems to be stronger. The preferential Th1 stimulation and increase in IFN-gamma production after vaccination may lead to a reduction in the humoral immune response which may explain the negative correlation between antibody production and T cell reactivity prior to vaccination.
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| 33. |
- Venge, Per, et al.
(författare)
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Blood biomarker algorithms for the diagnosis of mycoplasma pneumoniae respiratory infections
- 2021
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier. - 0022-1759 .- 1872-7905. ; 489
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Tidskriftsartikel (refereegranskat)abstract
- The correct diagnosis of acute infections as to bacteria, mycoplasma or virus is a clinical challenge and has a great impact on the therapeutic decisions. Current diagnostic tests of mycoplasma pneumoniae infections of the respiratory tract such as PCR and serology are either somewhat unreliable or slow and do not entirely meet the clinical needs of accurate and fast diagnosis. The aim of this report was to examine a panel of candidate biomarkers and their capacity to distinguish mycoplasma pneumoniae respiratory infections from respiratory infections caused by either bacterial or virus.Method: Patients with confirmed etiology of their acute respiratory infections (n = 156) were included of which 28 patients were diagnosed with mycoplasma pneumoniae. Blood was taken before any antibiotics treatment and analysed for Azurocidin (HBP), Calprotectin, CRP, Human Neutrophil Lipocalin (HNL), Interferon gamma-induced Protein 10 kDa (IP-10), Procalcitonin (PCT), Thymidine Kinase 1 (TK1), THE-Related Apoptosis-Inducing Ligand (TRAIL).Results: Individually the concentrations of IP-10, TK1 and P-HNL distinguished mycoplasma pneumoniae from bacterial infections with AUCs of 0.79-0.85. However, in combination, TK1 with either IP-10 or P-HNL showed an AUC of 0.97-0.95. In the distinction between mycoplasma pneumoniae and viral respiratory infections CRP, Calprotectin and TRAIL showed individual AUCs of 0.94-0.84. Together with either P-HNL dimer or PCT, CRP showed AUCs of 0.97.Conclusion: Our results indicate that it may be possible to design useful diagnostic algorithms of biomarkers that could help distinguish mycoplasma pneumoniae from respiratory infections caused by bacteria or virus. The development of rapid point-of-care assays based on such algorithms could be clinically useful tools in the therapeutic decision-making.
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| 34. |
- Venge, Per, et al.
(författare)
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HNL (Human Neutrophil Lipocalin) and a multimarker approach to the distinction between bacterial and viral infections
- 2019
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier. - 0022-1759 .- 1872-7905. ; 474
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The distinction between bacterial and viral causes of acute infections is a major clinical challenge. In this report we investigate the diagnostic performance in this regard of nine candidate biomarkers together with HNL (Human Neutrophil Lipocalin).METHODS: Blood was obtained from patients with symptoms of infectious (n = 581). HNL was measured in whole blood (B-HNL) after pre-activation with the neutrophil activator fMLP or in plasma (P-HNL). Azurocidin also known as heparin-binding protein (HBP), Calprotectin, PMN-CD64, CRP (C-reactive protein), IP-10 (Interferon γ-induced Protein 10 kDa), PCT (Procalcitonin), TK1 (Thymidine kinase 1), TRAIL (TNF-related apoptosis-inducing ligand) were measured in plasma/serum. Area under the ROC (receiver operating characteristics) curve (AuROC) was used for the evaluation of the clinical performance of the biomarkers.RESULTS: Side-by-side comparisons of the ten biomarkers showed large difference in the AuROC with B-HNL being the superior biomarker (0.91, 95% CI 0.86-0.95) and with the other nine biomarkers varying from AuROC of 0.63-0.79. The combination of B-HNL with IP-10 and/or TRAIL increased the diagnostic performance further to AuROCs of 0.94-0.97. The AuROCs of the combination of CRP with IP-10 and/or TRAIL were significantly lower than combinations with B-HNL 0.87 (95% CI 0.83-0.91).CONCLUSION: The diagnostic performance of whole blood activated HNL was superior in the distinction between bacterial or viral infections. The addition of IP-10 and/or TRAIL to the diagnostic algorithm increased the performance of B-HNL further. The rapid analysis of HNL, reflecting bacterial infections, together with biomarkers reflecting viral infections may be the ideal combination of diagnostic biomarkers of acute infections.
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| 35. |
- Venge, Per, et al.
(författare)
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Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections
- 2015
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 22:9, s. 1025-1032
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Tidskriftsartikel (refereegranskat)abstract
- The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P<0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P<0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.
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| 36. |
- Venge, Per, et al.
(författare)
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Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract
- 2017
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 24:7
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Tidskriftsartikel (refereegranskat)abstract
- The distinction between bacterial and viral causes of infections of the respiratory tract is a major but important clinical challenge. We investigated the diagnostic performance of human neutrophil lipocalin (HNL) in respiratory tract infections compared to those of C-reactive protein (CRP) and procalcitonin (PCT). Patients were recruited from the emergency department and from a primary care unit (n = 162). The clinical diagnosis with regard to bacterial or viral cause of infection was complemented with objective microbiological/serological testing. HNL was measured in whole blood after preactivation with the neutrophil activator formyl-methionine-leucine-phenylalanine (fMLP) (B-HNL), and CRP and PCT were measured in plasma. Head-to-head comparisons of the three biomarkers showed that B-HNL was a superior diagnostic means to distinguish between causes of infections, with areas under the concentration-time curve (AUCs) of receiver operating characteristic (ROC) analysis for HNL of 0.91 (95% confidence interval [CI], 0.83 to 0.96) and 0.92 (95% CI, 0.82 to 0.97) for all respiratory infections and for upper respiratory infections, respectively, compared to 0.72 (95% CI, 0.63 to 0.80) and 0.68 (95% CI, 0.56 to 0.79) for CRP, respectively (P = 0.001). In relation to major clinical symptoms of respiratory tract infections (cough, sore throat, stuffy nose, and signs of sinusitis), AUCs varied between 0.88 and 0.93 in those patients with likely etiology (i.e., etiology is likely determined) of infection, compared to 0.63 and 0.71 for CRP, respectively, and nonsignificant AUCs for PCT. The diagnostic performance of B-HNL is superior to that of plasma CRP (P-CRP) and plasma PCT (P-PCT) in respiratory tract infections, and the activity specifically reflects bacterial challenge in the body. The rapid and accurate analysis of HNL by point-of-care technologies should be a major advancement in the diagnosis and management of respiratory infections with respect to antibiotic treatment.
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| 37. |
- Venge, Per, et al.
(författare)
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Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections
- 2015
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 424, s. 85-90
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Tidskriftsartikel (refereegranskat)abstract
- The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) in serum distinguishes acute infections with high accuracy, but in the emergency setting the assay time should be <15-20 min, which excludes the use of serum samples. The aim was therefore to develop a novel rapid assay principle and test its clinical performance. Methods: Serum and neutrophils obtained from 84 infected and 20 healthy subjects were used in the experimental study. 725 subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the clinical study. HNL was measured in EDTA-plasma by ELISA or in heparinized whole blood after fMLP activation by a prototype point-of-care assay. Results: Increased release of HNL from neutrophils after activation with fMLP was seen already after 5 min incubation. The release of HNL from purified neutrophils after 15 min incubation with fMLP was significantly correlated to the HNL concentrations in serum obtained from the same patient (r = 0.74, p < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the ROC-curves were 0.95 (95% CI 0.91-0.97) and 0.88 (95% CI 0.84-0.91) for HNL in fMLP-activated whole blood and EDTA-plasma, respectively, (p <0.001) and in the distinction between bacterial and viral infections 0.91 (95% CI 0.86-0.95) and 0.76 (95% CI 0.70-0.81), respectively (p <0.001). Conclusion: The clinical performance of HNL in fMLP-activated whole blood was superior to HNL in EDTA-plasma and similar to HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.
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| 38. |
- Xu, Shengyuan, et al.
(författare)
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Tissue localization and the establishment of a sensitive immunoassay of the newly discovered human phospholipase B-precursor (PLB-P)
- 2010
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 353:1-2, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Human phospholipase B-precursor (PLB-P) is a newly identified and purified protein from human neutrophils. The precise function of PLB-P in vivo is not yet known. Its existence in neutrophils and the enzymatic activity against phospholipids imply a role in the defence against invading microorganisms and in the generation of lipid mediators of inflammation. We describe here the generation of specific antibodies against PLB-P, the tissue localizations of PLB-P and the establishment of an accurate, specific, and reproducible radioimmunoassay (RIA). A survey of normal and malignant tissues showed strong immunostaining of PLB-P in neuronal and myeloid cells and in adrenal glands. Elevated levels were found in sera of patients with influenza A infection i.e. > 1 mu g/L and in gut fluids of patients with inflammatory bowel disease i.e. > 20 mu g/L. The levels correlated to markets of neutrophil activation, suggesting a neutrophil origin of PLB-P in these conditions. The antibodies and the assay will be useful in the future basic and clinical investigations of PLB-P.
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| 39. |
- Xu, S. Y., et al.
(författare)
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Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections
- 1995
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 55:2, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- Human neutrophil lipocalin (HNL) is a recently identified protein from human neutrophil granules. The concentrations of HNL in the circulation were measured, in a group of patients with acute infections, using a radioimmunoassay. The concentrations of HNL in patients infected by viruses and bacteria were 93.78 +/- 45.30 micrograms l-1 (SD), 404.14 +/- 355.02 micrograms l-1 (SD) in serum, and 47.81 +/- 18.18 micrograms l-1 (SD), 145.46 +/- 194.32 micrograms l-1 (SD) in plasma, respectively. The differences between the two patient groups were highly significant. There was a significant correlation between serum HNL and plasma HNL levels in bacterial infections (r = 0.73, p < 0.0001). The HNL serum levels also correlated with those of C-reactive protein (CRP) (r = 0.59, p < 0.0001). Determination of HNL in serum was more specific and sensitive than CRP in the distinction between viral and bacterial infections. At a cut-off of 155 micrograms l-1 (HNL in serum), the positive and negative predictive values for the diagnosis of bacterial infections were 92 and 96%, respectively, which were superior to the optimal predictive values of CRP. Thus, the determination of HNL level is useful in the diagnosis of acute bacterial infections.
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