| 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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| 4. |
- de Ståhl, Teresita Díaz, et al.
(författare)
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Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array
- 2008
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 29:3, s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
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| 5. |
- 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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| 6. |
- Elbagir, Sahwa, et al.
(författare)
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Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies
- 2020
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 29:5, s. 463-473
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities.Methods: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females.Results: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased.Conclusions: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.
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| 7. |
- 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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| 8. |
- ElShafie, Amir Ibrahim, 1970-, et al.
(författare)
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Active Rheumatoid Arthritis in Central Africa : A Comparative Study Between Sudan and Sweden
- 2016
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:10, s. 1777-1786
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare clinical characteristics and treatment between simultaneously investigated Sudanese and Swedish outpatients with rheumatoid arthritis (RA).Methods. Outpatients with RA from Sudan (n = 281) and Sweden (n = 542) diagnosed according to the 1987 American College of Rheumatology criteria were recruited between December 2008 and September 2010 and compared concerning clinical presentation, treatment, and laboratory findings, including immunoglobulin M with rheumatoid factor (IgM-RF).Results. Sudanese patients had lower inclusion age (median 49 vs 68 yrs), disease duration (48 vs 107 mos), and disease onset age (43 vs 56 yrs) as compared with Swedish patients (p < 0.0001 for all). When stratified concerning the age of inclusion, Swedish patients between 41-50 years had, however, a significantly lower age of onset, with a similar trend for all age groups above 30 years. The female preponderance was higher among Sudanese patients (89.3% vs 72.5%, p < 0.0001), and smoking was nonexistent among Sudanese female patients (p < 0.0001). Erythrocyte sedimentation rate levels and number of tender joints were significantly higher among Sudanese patients. The proportion of IgM-RF positivity was lower among Sudanese patients with RA (52.4% vs 75.5%, p < 0.0001). Higher proportions of Sudanese patients with RA were treated with methotrexate (MTX) and disease-modifying antirheumatic drug combinations, but none of them used biologics. Sudanese patients used lower doses of MTX and sulfasalazine (p < 0.0001) and higher doses of prednisolone (p < 0.0001) than Swedish patients.Conclusion. Sudanese patients with RA have significantly higher disease activity and are often IgM-RF-seronegative. Together with reports from Uganda and Cameroon, our data indicate a cluster of highly active and often seronegative RA in central Africa.
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| 9. |
- Elshafie, Amir I., et al.
(författare)
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Activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis
- 2011
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Ingår i: International Journal of Parasitology. - : Elsevier BV. - 0020-7519 .- 1879-0135. ; 41:3-4, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P = 0.0001 and P = 0.002, respectively). Serum-ECP levels were higher in the controls (P < 0.0001), while plasma MPO levels were higher in the VL group (P < 0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P < 0.0001, P = 0.017 and P = 0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P < 0.0001 and P = 0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P < 0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.
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| 10. |
- ElShafie, Amir Ibrahim, 1970-, et al.
(författare)
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Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity among Sudanese patients with rheumatoid arthritis
- 2019
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Ingår i: Clinical Rheumatology. - : SPRINGER LONDON LTD. - 0770-3198 .- 1434-9949. ; 38:6, s. 1545-1553
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort. Methods Consecutive RA patients (n=281) diagnosed according to the 1987 ACR criteria were included 2008-2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls. Results IgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8years lower median age of disease onset compared to antibody negative patients (p<0.0001). IgG RF was the only marker associated with a high number of involved joints (p=0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p=0.016 and p=0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies. Conclusion Whereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.
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| 11. |
- Elshafie, Amir I., 1970-
(författare)
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The Immunopathology of Rheumatoid Arthritis and Leishmania donovani Infection in Sudan
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Immune complexes (IC) and antibody production against self-antigens play a pathological key role in the development of autoimmunity that occurs in patients with parasitic infections and rheumatic diseases. My studies have targeted two groups of patients from Sudan; patients with visceral leishmaniasis (VL) and patients with rheumatoid arthritis (RA).In VL patients I studied the functional role of IC and IC-induced cytokine production in the pathogenesis of the disease and their effect on kidney functions. For the Sudanese RA cohort, I performed a comparative study with Swedish RA patients. I also investigated the Sudanese RA cohort for the occurrence of RA-associated autoantibodies (rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA)) and the diagnostic and prognostic impact of these autoantibodies on the clinical outcome.In the VL project, I demonstrated that Sudanese VL patients had elevated serum levels of IC and of IC-induced cytokine levels in vitro. GM-CSF levels were increased in acute VL patients and in VL patients with ongoing sodium stibogluconate treatment, and the only cytokine that correlated to a high degree with circulating IC levels. Cystatin C was shown to be a superior marker of glomerular function as compared to serum creatinine in VL patients. For the RA project, a comparative study was performed in collaboration with the rheumatology unit at Gävle hospital. We concluded that the clinical picture of RA in Sudan was more severe, with more widespread joint involvement and stronger laboratory signs of inflammation when compared to the Swedish RA patients.ACPA and RF are both included in the new 2010 RA classification criteria. In many RA studies over the world the occurrence of ACPA and RF varies considerably, this may be due to both geographical differences and lack of standardization for RF and anti-CCP in the RA criteria. But in this study we aligned all antibodies to the same diagnostic specificity compared to Sudanese healthy controls. When doing so we determined that IgA RF had the highest diagnostic sensitivity, a finding that differs from Caucasian studies in which IgM RF predominates. IgG RF was also the autoantibody most strongly associated with early age of disease onset and hand deformities, a clinical picture that differs in most Caucasian studies in which ACPA are the strongest markers for bad prognosis. Thus data from this Sudanese RA cohort implies significant clinical and immunological differences compared to Caucasian RA patients.
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| 12. |
- Åhlin, Erik, et al.
(författare)
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Anti-Citrullinated Peptide Antibodies in Sudanese Patients with Leishmania donovani Infection Exhibit Reactivity not Dependent on Citrullination
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 81:3, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- African patients with Leishmania donovani infections have signs of strong systemic inflammation and high levels of circulating immune complexes (IC) and rheumatoid factor (RF), all serologic markers of rheumatic disease. As inflammation in general is associated with citrullination, we sought to investigate ACPA responses in Sudanese Leishmania patients. Serum samples were collected from Sudanese patients with visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) as well as from ACPA-positive Sudanese rheumatoid arthritis patients and compared to healthy Sudanese controls. Levels of circulating C1q-binding IC and anticyclic citrullinated peptide 2(CCP2) were investigated using ELISA, and RF was measured with nephelometry. C1q adsorption was carried out to investigate anti-CCP2 content in IC. Citrulline specificity was evaluated with control plates with cyclic arginine-containing control peptides. Leishmania-infected patients had elevated levels of RF and circulating IC but also a significant increase in anti-CCP2 (12%) as compared to healthy controls. Anti-CCP2-positive Leishmania patients displayed lower anti-CCP2 levels than Sudanese patients with rheumatoid arthritis (RA), and anti-CCP2 levels in Leishmania patients showed a continuum not resembling the dichotomous pattern seen in patients with RA. Whereas the anti-CCP reactivity of Sudanese RA sera was strictly citrulline dependent, anti-CCP2-positive Leishmania sera reacted equally well with ELISA plates containing arginine control peptides. There was a strong correlation between anti-CCP2 and circulating IC among the Leishmania patients, but IC depletion only marginally diminished anti-CCP2 levels. Our findings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions associated with macrophage activation.
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