| 1. |
- Brodszki, Nicholas, et al.
(författare)
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Immune responses following meningococcal serogroups A, C, Y and W polysaccharide vaccination in C2-deficient persons: Evidence for increased levels of serum bactericidal antibodies.
- 2015
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 33:15, s. 1839-1845
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Tidskriftsartikel (refereegranskat)abstract
- Complement C2 deficiency (C2D) is associated with immunological diseases and increased susceptibility to invasive infections caused by encapsulated bacteria such as Neisseria menigitidis. In this study we evaluate the immunogenicity of vaccination against N. menigitidis in C2D. C2D patients (n=22) and controls (n=52) were given a tetravalent meningococcal polysaccharide vaccine. Serum bactericidal antibody (SBA) titres (serogroups A, C, Y and W) were analysed using a rabbit complement source. Levels of IgG, IgM, and IgA, factor B, and factor H, polymorphisms of MBL and Fc-gamma receptors were determined. The C2D patients responded with an increased SBA titre to all four serogroups (p<0.001). The response rates define as SBA titres ≥8 were found to be between 85.7% and 92.5%. The post-vaccination titres for serogroups C, Y and W were equal to healthy controls. C2D patients with a history of invasive infection had a lower post-vaccination SBA titres both compared to healthy C2D persons (p=0.03) and compared to controls (p<0.0001). We found that the G2M*n/G2M*n genotype were associated with a higher SBA titres after immunization (p=0.03). None of the other investigated immunological factors appear to be important in influencing the vaccine responses. Autoimmune diseases in C2D did not affect the vaccine response. In general, vaccination against meningococci gave rise to antibody responses in the C2D patients that equal healthy controls. The response rate was lower to serogroup A and among C2D patients with history of invasive infections. The presence of G2M*n/G2M*n genotype was associated with higher SBA titres after immunization.
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| 2. |
- Genel, Ferah, et al.
(författare)
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Inherited Classical and Alternative Pathway Complement Deficiencies in Children : A Single Center Experience
- 2018
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Ingår i: Iranian journal of immunology : IJI. - 1735-1383. ; 15:4, s. 309-320
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary complement deficiencies are rare diseases. OBJECTIVE: To retrospectively evaluate the clinical and laboratory findings and complications of patients to increase awareness of pediatricians about complement deficiencies, which are rarely encountered. METHODS: In this study, the clinical and immunological characteristics of 21 patients who consulted the Immunology Department of our hospital between 2003 and 2017 and were diagnosed with classical or alternative pathway complement deficiency were obtained from the file records. RESULTS: Ten patients with C1 inhibitor deficiency, four patients with factor I deficiency, three patients with properdin deficiency, two patients with C8 deficiency, one patient with C1q deficiency, and one patient with C4B deficiency were assessed. The mean age of the patients at diagnosis was 11.4±4.7 years, the age of onset of symptoms was 7.9±3.9 years, and the follow-up period was 6.7±3.9 years. Fourteen cases had a similar medical history in the family. All patients with C1q, factor I, properdin, C8, and C4B deficiencies presented with an infection, and vasculitic rash was present in two patients with factor I deficiency. In addition, immune complex glomerulonephritis was present in one patient with factor I deficiency. Meningococcal, Haemophilus influenzae type B, and pneumococcal vaccines were administered and prophylactic antibiotic treatment was initiated in all patients except patients with C1 inhibitor deficiency. CONCLUSIONS: Early diagnosis of complement deficiencies can facilitate prevention of life-threatening complications such as severe bacterial infections by considering prophylactic antibiotics and vaccines. In patients with C1 inhibitor deficiency, achieving an acurate early diagnosis will assist in the management and timely treatment of life-threatening attacks such as upper airway obstruction and improve outcomes.
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| 3. |
- Gustavsen, Alice, et al.
(författare)
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Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome
- 2017
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Ingår i: Medicine. - 0025-7974. ; 96:11
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Antiphospholipid syndrome (APS) in pregnancy may trigger the life-threatening catastrophic antiphospholipid syndrome (CAPS). Complement activation is implicated in the pathogenesis, and inhibition of complement factor C5 is suggested as an additional treatment option. Patient concerns, diagnosis and interventions: We present a pregnant patient treated with the C5-inhibitor eculizumab due to high risk of developing devastating APS-related complications. The complement inhibitory effects of the treatment were examined both in the patient and the premature infant. Outcomes: Complement activity in the mother recovered considerably faster than anticipated; however, no new thrombosis or CAPS developed during the last week of pregnancy or postpartum. Blood sampling from the umbilical vein and artery, and from the infant after delivery showed low complement activity; however, only 0.3% of the eculizumab concentration detected in the mother, consistent with low placental passage of eculizumab. Lessons: The data underscore the importance of close monitoring of complement inhibition and individualizing dosage regimens in pregnant patients receiving eculizumab. We document how traditional functional complement activity tests cannot assess the effect of eculizumab in premature infants due to the very low levels of complement factors detected in this infant born in gestational week 33. Only trace amounts of eculizumab passed the placenta. In conclusion, complement C5 inhibition might be a safe candidate treatment option for APS during pregnancy and delivery, and additionally, enables prolongation of pregnancy with important weeks.
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| 4. |
- Hamsten, C., et al.
(författare)
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Heat differentiated complement factor profiling
- 2015
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 126, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.
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| 5. |
- Hesselstrand, Roger, et al.
(författare)
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Immunogenicity and safety of pneumococcal vaccination in patients with systemic sclerosis
- 2018
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 57:4, s. 625-630
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the impact of disease and treatment with DMARDs on antibody response elicited by either pneumococcal conjugate vaccine (PCV13) or pneumococcal polysaccharide vaccine (PPV23) in patients with SSc. Methods. Forty-four SSc patients and 49 controls received a dose of either PCV13 or PPV23. Twelve patients were treated with DMARDs. Antibody levels to pneumococcal polysaccharides 6B and 23 F were measured before and 4-6 weeks after vaccination using ELISA. Antibody functionality was studied using opsonophagocytic assay performed on serotype 23 F. Results. Number of patients, percentage female and mean age (years) at vaccination were: 32, 94%, 57.5 years in SSc without DMARDs; 12, 100%, 55.5 years in SSc on DMARDs and 49, 63% and 50.6 years in controls. Post-vaccination antibody levels for both serotypes increased significantly in SSc without DMARDs and controls (P < 0.001), but in SSc on DMARDs only for 6B (P = 0.041). Compared with the other groups, patients with SSc receiving DMARDs had lower post-vaccination antibody levels for both serotypes. Opsonophagocytic assay increased significantly in all three groups. No significant difference in immunogenicity between PCV13 and PPV23 was seen. Conclusion. Pneumococcal vaccination using either PCV13 or PPV23 yielded satisfactory antibody response in SSc patients without DMARD treatment, but a lower response in patients treated with synthetic DMARDs. Type of pneumococcal vaccine (conjugate or polysaccharide) did not significantly influence antibody response.
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| 6. |
- Nagel, Johanna, et al.
(författare)
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Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.
- 2017
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 26:10, s. 1072-1081
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: The objective of this study was to explore the impact of systemic lupuserythematosus and belimumab given in addition to standard of care therapy on 13-valentconjugated pneumococcal vaccine (PCV13) response. Methods: Forty-seven systemic lupuserythematosus patients and 21 healthy controls were immunized with a single dose of13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patientswere treated with traditional disease-modifying anti rheumatic drugs, 11 of those receivedbelimumab in addition, and 32 patients were treated with concomitant prednisolone.Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharideswas performed in serum taken before and four to six weeks after vaccination using multiplexfluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were alsoanalyzed using standard enzyme-linked immunosorbent assays. Opsonophagocyticassay was performed on serotype 23F to evaluate the functionality of the antibodies. Preandpost-vaccination log transformed antibody levels were compared to determine theimpact of systemic lupus erythematosus diagnosis and different treatments on antibodyresponse. Results: Systemic lupus erythematosus patients as a group showed lower postvaccinationantibody levels and lower fold increase of antibody levels after vaccinationcompared to controls (p¼0.02 and p¼0.009, respectively). Systemic lupus erythematosuspatients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquinedid not differ compared to controls, whereas the other treatment groups hadsignificantly lower fold increase of post-vaccination antibody levels. Higher age was associatedwith lower post-vaccination antibody levels among systemic lupus erythematosuspatients. Conclusion: Belimumab given in addition to traditional disease-modifyinganti rheumatic drugs or prednisolone did not further impair antibody response to 13-valentconjugated pneumococcal vaccine.
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| 7. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Interpretation of Serological Complement Biomarkers in Disease
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Complement systemaberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.
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| 8. |
- Nived, Per, et al.
(författare)
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Antibody response to 13-valent pneumococcal conjugate vaccine is not impaired in patients with rheumatoid arthritis or primary Sjögren’s syndrome without disease modifying treatment
- 2018
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Ingår i: BMC Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 2, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pneumococcal vaccination is recommended to patients with rheumatoid arthritis (RA) and primary Sjögren’s syndrome (pSS). However, little is known whether the diseases influence pneumococcal vaccine response. This study aimed to investigate antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in RA patients or pSS patients without disease modifying anti-rheumatic drugs (DMARD), compared to patients with RA treated with DMARD or to healthy controls. Methods: Sixty RA patients (50 without DMARD and 10 with MTX), 15 patients with pSS and 49 controls received one dose of PCV13. Serotype-specific antibody concentrations for pneumococcal polysaccharides 6B and 23F and functionality of antibodies (23F) were determined in serum taken before and 4–6 weeks after vaccination using ELISA and opsonophagocytic activity assay (OPA), respectively. Proportions of individuals with positive antibody response (i.e. ≥ 2-fold increase from prevaccination concentrations; antibody response ratio; ARR ≥ 2), percentage of individuals reaching putative protective antibody level (i.e. ≥1.3 μg/mL) for both serotypes, and difference in OPA were calculated. Results: After vaccination, antibody concentrations for both serotypes increased in RA without DMARD (p < 0.001), pSS (p ≤ 0.05 and < 0.01) and controls (p < 0.001). Antibody responses to 6B and 23F were comparable in RA without DMARD (64% and 74%), pSS (67% and 53%) and controls (65% and 67%), but lower in the small group RA with MTX (both 20%, p < 0.01). Similarly, significant increases of patients reaching protective antibody levels were seen in RA without DMARD (p ≤ 0.001) and controls (p < 0.001). After vaccination, OPA increased significantly in controls, RA and pSS without DMARD (p < 0.001 to 0.03), but not in RA with MTX. Conclusions: Pneumococcal conjugate vaccine is immunogenic in RA and pSS patients without DMARD and in line with previous studies we support the recommendation that vaccination of RA patients should be performed before the initiation of MTX.
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| 9. |
- Nived, Per, et al.
(författare)
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Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy
- 2017
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 35:29, s. 3639-3646
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls. Methods: 49 patients with vasculitis and 49 controls received a single dose (0.5. ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n = 11), cyclophosphamide (CYC; n = 6), methotrexate (MTX; n = 9), rituximab (n = 3); anti-TNF (n = 2), mycophenolate mofetil (n = 2), prednisolone alone (n = 15) and no active treatment (n = 2). Specific antibody concentrations for serotypes 6B and 23F were determined using ELISA and opsonophagocytic activity (OPA) assay (23F) was performed, on serum samples taken immediately before and 4-6. weeks after vaccination. Proportion of individuals with putative protective antibody concentration (≥1.0. μg/mL) and positive antibody response (≥2-fold increase from prevaccination concentration) for both serotypes were calculated and groups were compared. Results: At baseline, 6 patients (12%) and 12 controls (24%) had protective antibody levels for both serotypes. After vaccination, antibodies increased for both serotypes in patients and controls (p <. 0.001), 32 patients (65%) and 35 controls (71%) reached protective level for 6B, and 32 patients (65%) and 37 controls (76%) for 23. F. Compared to controls, patients had lower prevaccination geometric mean concentration (23F, p = 0.01) and a numerical trend towards lower prevaccination level (6B) and postvaccination levels (both serotypes). Patients with prednisolone alone had lower prevaccination OPA (p <. 0.01) compared to controls. OPA increased after vaccination in both patients and controls (p <. 0.001), but improvement was better in controls (p = 0.001). AZA, CYC or MTX, but not prednisolone alone, tended towards a lower proportion of patients reaching protective antibody levels (p = 0.06), compared to controls. Conclusions: Pneumococcal conjugate vaccine was safe and immunogenic in patients with established vasculitis. Treatment with DMARDs, mostly AZA, CYC and MTX but not systemic prednisolone may impair antibody response. Trial registration. ClinicalTrials.gov Identifier: NCT02240888. Registered 4 September, 2014.
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| 10. |
- Ohlsson, Sophie, et al.
(författare)
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Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6, s. 0218272-0218272
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Tidskriftsartikel (refereegranskat)abstract
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway. C5a-primed neutrophils (PMN) from 10 AAV patients and 10 healthy controls (HC) were stimulated with PMA or IgG purified from PR3-ANCA positive patients (ANCA IgG). The supernatants were analyzed for release of complement proteins and markers of different granules by ELISA, and release of microparticles (MP) by flow cytometry. The ability of the supernatants to activate the alternative complement pathway was determined by incubation with normal serum and C3bBbP and C5a were measured by ELISA. MP were analyzed by flow cytometry and removed by centrifugation. The supernatants from the AAV patients' neutrophils produced significantly more C3bBbP compared with HCs (p = 0.0001). C3bBbP levels correlated with the number of MP. After removal of MP from the supernatants, alternative pathway activation was significantly lower. This study shows that primed and ANCA-stimulated neutrophils from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls. This finding emphasizes the role of complement in the pathogenesis of AAV - underlining the therapeutic potential of C5a and other complement blockade.
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