| 11. |
- Bengtsson, Anders, et al.
(författare)
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Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies
- 2000
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 9:9, s. 664-671
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the relation between serum levels of interferon-alpha (IFN-alpha), the activity of an endogenous IFN-alpha inducing factor (SLE-IIF), clinical and immunological disease activity as well as serum levels of antiretroviral antibodies in SLE. Serum levels of IFN-alpha were measured in serial sera from 30 patients sampled at different stages of disease activity (SLEDAI score). The SLE-IIF activity was measured by its ability to induce IFN-alpha production in cultures of normal peripheral blood mononuclear cells. Both serum IFN-alpha and SLE-IIF increased markedly at flare in serially followed patients. The SLEDAI score, levels of anti-dsDNA antibodies and IL-10 correlated positively, and complement components Clq, C3 and leukocytes correlated inversely with serum concentrations of IFN-alpha. The extent of multiple organ involvement correlated with serum IFN-alpha. No relation between concentrations of retroviral peptide binding antibodies and IFN-alpha or SLE-IIF activity was found. The close relationship between disease activity in SLE patients and IFN-alpha serum levels suggests that activation of the type 1 IFN system might be of importance in the disease process.
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| 12. |
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| 13. |
- Bengtsson, Anders, et al.
(författare)
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SLE serum induces classical caspase-dependent apoptosis independent of death receptors
- 2008
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 126:1, s. 57-66
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Tidskriftsartikel (refereegranskat)abstract
- The main source of autoantigens in systemic lupus erythematosus (SLE) is most likely apoptotic material. We have previously shown that sera from SLE patients can induce apoptosis in monocytes and lymphocytes, and here we characterized mechanisms of apoptosis induced by SLE serum. SLE serum seems to induce caspase-dependent classical apoptosis since cells exposed to SLE serum displayed morphology consistent with classical apoptosis as demonstrated by confocal microscopy, and pan-caspase inhibitor Z-VAD.fmk significantly reduced SLE serum-induced apoptosis. Death-receptor-independent pathways seemed to be involved since SLE serum induced apoptosis equally in FADD-mutant and wild-type Jurkat cell lines, and blocking of Fas and TNFR1 did not reduce apoptosis induction. Importantly, apoptosis was significantly reduced in a Bcl-2 overexpressing Jurkat cell line indicating involvement of mitochondrial pathways. Thus, based on morphology and caspase inhibition experiments, we have demonstrated that SLE serum induce classical caspase-dependent apoptosis, and this was independent of death receptor pathways.
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| 14. |
- Brodszki, Nicholas, et al.
(författare)
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Novel Genetic Mutations in the First Swedish Patient with Purine Nucleoside Phosphorylase Deficiency and Clinical Outcome After Hematopoietic Stem Cell Transplantation with HLA-Matched Unrelated Donor.
- 2015
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Ingår i: JIMD Reports. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 2192-8304. ; 24, s. 9-83
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Tidskriftsartikel (refereegranskat)abstract
- Purine nucleoside phosphorylase (PNP) is an enzyme active in the purine salvage pathway. PNP deficiency caused by autosomal recessive mutations in the PNP gene leads to severe combined immunodeficiency (SCID) and in two thirds of cases also to neurological effects such as developmental delay, ataxia, and motor impairment.PNP deficiency has a poor outcome, and the only curative treatment is allogenic hematopoietic stem cell transplantation (HSCT). We present the first Swedish patient with PNP deficiency with novel mutations in the PNP gene and the immunological results of the HSCT and evaluate the impact of HSCT on the neurological symptoms. The patient presented early in life with neurological symptoms and suffered later from repeated serious respiratory tract infections. Biochemical tests showed severe reduction in PNP activity (1% residual activity). Genetic testing revealed two new mutations in the PNP gene: c.729C>G (p.Asn243Lys) and c.746A>C (p.Tyr249Cys). HSCT was performed with an unrelated donor, resulting in prompt and sustained engraftment and complete donor chimerism. There was no further aggravation of the patient's neurological symptoms at 21 months post HSCT, and appropriate developmental milestones were achieved. HSCT is curative for the immunological defect caused by PNP deficiency, and our case strengthens earlier reports that HSCT is effective as a treatment even for neurological symptoms in PNP deficiency.
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| 15. |
- Brodszki, Nicholas, et al.
(författare)
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Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions.
- 2016
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID); although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells.
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| 16. |
- Brodszki, Nicholas, et al.
(författare)
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Primary immunodeficiency in infection-prone children in southern Sweden: occurrence, clinical characteristics and immunological findings.
- 2014
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders mainly characterized by increased susceptibility to infections. The aims of this study were to estimate the occurrence rate of PID in the paediatric (age ≤ 18 years) population of southern Sweden (approx. 265,000 children) and to describe their demographic, clinical and immunological characteristics. During a period of 4 years, in four paediatric speciality clinics in Skåne County in southern Sweden, children being seen for infections and fulfilling specific criteria were evaluated according to a predefined examination schedule. The initial analysis consisted of complete blood counts with analysis of lymphocyte subpopulations (T, B, NK cells), measurement of immunoglobulins (IgG, IgA, IgM, IgE and IgG subclasses), and assessment of the complement system (classical, alternative and lectin pathways). In addition, results of these immunological analyses in other children from the same area and time period were evaluated.
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| 17. |
- Börjesson, Anna, et al.
(författare)
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Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats.
- 2002
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Ingår i: Digestive and Liver Disease. - 1590-8658. ; 34:3, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intestinal ischaemia-reperfusion can lead to pulmonary injury characterised by increased macromolecular leakage and leukocyte sequestration. Important mediators of ischaemia-reperfusion-associated injury include polymorphonuclear granulocytes and platelet-activating factor. AIM: To investigate the potential therapeutic inhibition of platelet-activating factor in intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent platelet-activating factor-receptor antagonist, lexipafant. METHODS: Rats were subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes reperfusion. RESULTS: Increased leakage of radiolabelled human serum albumin was found in the lungs after intestinal ischaemia followed by 3 or 12 hours reperfusion. Administration of lexipafant did not significantly prevent the increased leakage. Pulmonary myeloperoxidase content increased after intestinal ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration through the pulmonary endothelium. The increase in interleukin-1beta seen after 3 hours reperfusion was partly reversed by lexipafant. CONCLUSIONS: Pulmonary injury occurred following intestinal ischaemia-reperfusion, characterised by increased leakage of radiolabelled albumin over the endothelial barrier; correlating with increased pulmonary myeloperoxidase-content, implying involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly decrease severity of pulmonary damage.
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| 18. |
- C Kapetanovic, Meliha, et al.
(författare)
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Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors
- 2011
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:12, s. 3723-3732
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. Methods. Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n = 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscu-larly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays. Results. Positive antibody response was defined as an antibody response ratio (ARR) (i. e., ratio of post-to prevaccination antibody levels) of > 2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P = 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA. Conclusion. Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses.
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| 19. |
- C Kapetanovic, Meliha, et al.
(författare)
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Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs.
- 2011
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 1434-9949 .- 0770-3198. ; 30:12, s. 1555-1561
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR.
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| 20. |
- C Kapetanovic, Meliha, et al.
(författare)
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Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis.
- 2006
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 45:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax (R)) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. Methods. Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. Results. Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P < 0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. Conclusions. Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.
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