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- Elbagir, Sahwa, 1983-
(författare)
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Autoimmunity in Africa: Comparing Systemic Lupus Erythematosus and Anti-phospholipid Antibodies in Sudan and Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic Lupus Erythematosus (SLE) is a chronic immune complex (IC)-mediated disease with variable prevalence worldwide, reported to be more common in Africans, Hispanics and Asians than in Caucasian populations. Expression of autoantibodies might vary between different ethnic populations due to environmental and genetic factors. Antiphospholipid antibodies (aPL) react with several antigenic targets of negatively charged phospholipids and/or associated plasma proteins. In this thesis we have studied the immunological and clinical characteristics of SLE in patients from Sudan and Sweden using an identical methodology. We have also investigated the occurrence of aPL during healthy pregnancies in both countries.Sudanese patients with SLE were younger, had shorter disease duration and suffered from more organ damage compared to Swedish patients. Neurological involvement, predominantly in young patients, was the main contributor to organ damage among the Sudanese patients. When comparing anti-nuclear antibody (ANA) specificities in IC between Sudanese and Swedish patients, different results from ANA detected in serum was observed. While serum ANA levels were mainly higher in Swedish SLE patients, levels of most ANA specificities in IC, particularly anti-chromatin specificities, were increased in Sudanese patients. In both cohorts, ANA in IC associated with more active SLE. Sudanese SLE patients had a higher prevalence of IgA aPL using common assay cut-off points. However, aPL levels among controls were also higher in Sudan, and when cut-offs were adjusted based on national controls the difference in prevalence between the patient groups was no longer evident. A more recently defined test measuring antibody against the phosphatidylserine/prothrombin complex was the best aPL predictor of thrombosis in Swedish SLE patients, independent of cardiovascular risk factors and antiphospholipid antibody syndrome criteria tests. Levels of IgA aPL, particularly anti-β2 glycoprotein I, were higher in normal pregnancies of healthy women from Sudan. This was not observed in Swedish pregnancies, and it was not due to reactivity against domain 1 of the β2 glycoprotein I molecule.Levels of autoantibodies differed both for patients and healthy individuals from Sudan and Sweden, and the occurrence of antibodies among patients depended on the cut-offs used. Adjustments to national cut-offs revealed more associations between autoantibody occurrence and clinical manifestations in Sudan. We recommend that the evaluation of autoantibody prevalence and clinical significance in autoimmune diseases in populations of African origin should rely on cut-offs based on controls from the same population, both in research and clinical contexts.
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| 2. |
- Gunnarsson, Iva
(författare)
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SLE : pathogenetic mechanisms in nephritis and sulphasalazine-induced lupus reactions
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with a multifactorial and largely unknown etiology, in which genetic and environmental factors are known to influence disease susceptibility and expression. Nephritis is a common and severe disease manifestation in which immune complexes and complement deposits in the renal tissue are invariably seen. Anti-C1q antibodies are known to associate with proliferative forms of lupus nephritis. One aim of these studies has been to investigate pathogenetic mechanisms of lupus nephritis, in particular the role of C1q, the first subcomponent of the classical complement cascade, and autoantibodies directed against this molecule. We also aimed to define predisposing factors and underlying pathogenetic mechanisms in sulphasalazine-induced SLE, and to determine the possibility of pathogenetic similarities between idiopathic and sulphasalazine-induced SLE. In studies of ongoing IgG anti-C1q antibody production in peripheral blood mononuclear cells, high levels of IgG anti-C1q producing cells were recorded exclusively in patients with biopsy-proven proliferative lupus nephritis, thus indicating a pathogenetic role. Active production of anti-C1q antibodies was found to be superior in the prediction of proliferative nephritis as compared to analysis of antibodies in the serum. IgA anti-C1q antibodies were detected in patients with the immune complex-associated IgA nephropathy, indicating pathogenetic similarities with SLE nephritis. In a follow-up study of patients with proliferative lupus nephritis, a high proportion of patients still had histological evidence of active renal disease at repeated biopsy after six months of therapy, despite intensive immunosuppressive treatment and apparent clinical improvement. Low serum C1q levels at both first and repeated biopsy predicted and associated with an unfavourable histological outcome. Beneficial prognostic factors at repeated biopsy were determined as low-grade proteinuria, normal C1q, levels and the absence of anti-C1q antibodies. As for the role of predisposing factors in the development of sulphasalazine-induced SLE, slow acetylator genotype of N-acetyltransferase 2, HLA haplotypes in accordance with idiopathic SLE and enhanced IL-10 levels in serum were identified as factors associated with an increased susceptibility to development of lupus-like disease. In contrast to drug-induced SLE in general, anti-dsDNA was a common feature of sulphasalazine-induced SLE. Development of nephritis and persistent SLE occurred after high cumulative dose and long-term treatment with sulphasalazine. Similar pathogenetic mechanisms may be operative in both idiopathic and sulphasalazine-induced SLE, suggesting that sulphasalazine may act as an immunomodulator in genetically predisposed individuals.
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