| 1. |
- Elbagir, Sahwa, et al.
(författare)
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Sudanese and Swedish patients with systemic lupus erythematosus : immunological and clinical comparisons
- 2020
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 59:5, s. 968-978
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: SLE is known to have an aggressive phenotype in black populations, but data from African cohorts are largely lacking. We therefore compared immunological and clinical profiles between Sudanese and Swedish patients using similar tools.METHODS: Consecutive SLE patients from Sudan (n = 115) and Sweden (n = 340) and from 106 Sudanese and 318 Swedish age- and sex-matched controls were included. All patients fulfilled the 1982 ACR classification criteria for SLE. Ten ANA-associated specificities and C1q-binding immune complexes (CICs) were measured. Cut-offs were established based on Sudanese and Swedish controls, respectively. Disease activity was measured with a modified SLEDAI and organ damage with the SLICC Damage Index. In a nested case-control design, Swedish and Sudanese patients were matched for age and disease duration.RESULTS: Females constituted 95.6% and 88.1% of Sudanese and Swedish patients, respectively (P = 0.02), with younger age at inclusion (33 vs 47.7 years; P < 0.0001) and shorter disease duration (5 vs 14 years; P < 0.0001) among Sudanese patients. Anti-Sm antibodies were more frequent in Sudanese patients, whereas anti-dsDNA, anti-histone and CICs were higher in Swedish patients. In the matched analyses, there was a trend for higher SLEDAI among Swedes. However, Sudanese patients had more damage, solely attributed to high frequencies of cranial/peripheral neuropathy and diabetes.CONCLUSION: While anti-Sm is more common in Sudan than in Sweden, the opposite is found for anti-dsDNA. Sudanese patients had higher damage scores, mainly because of neuropathy and diabetes. Sudanese patients were younger, with a shorter SLE duration, possibly indicating a more severe disease course with impact on survival rates.
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| 2. |
- Langefeld, Carl D., et al.
(författare)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 3. |
- 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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| 4. |
- Elbagir, Sahwa, et al.
(författare)
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High IgA anti-phospholipid autoantibodies in healthy Sudanese explains the increased prevalence among Sudanese compared to Swedish systemic lupus erythematosus patients
- 2020
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Ingår i: Lupus. - : Sage Publications. - 0961-2033 .- 1477-0962. ; 29:11, s. 1412-1422
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: IgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs.Methods: Consecutive SLE patients and age- and sex-matched controls from Sudan (N = 115/106) and Sweden (N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome-related events were obtained from patients' records. IgA/G/M anticardiolipin and anti-β2 glycoprotein I (β2GPI) were analysed with two independent assays. IgA anti-β2GPI domain 1 (D1) was also investigated. Manufacturers' cut-offs and the 95th and 99th percentile cut-offs based on national controls were used.Results: Sudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers' cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-β2GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts.Conclusions: IgA anti-β2GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers' cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach.
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| 5. |
- Grönwall, Caroline, et al.
(författare)
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A Comprehensive Evaluation of the Relationship Between Different IgG and IgA Anti-Modified Protein Autoantibodies in Rheumatoid Arthritis
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.
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