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.

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 &lt; 0.0001) and shorter disease duration (5 vs 14 years; P &lt; 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.

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.

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 8 years 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.

Objectives Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β2glycoprotein I (anti-β2GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures.

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.

The role of anti-nuclear autoantibody (ANA) specificities in immune complexes (IC) formation has been studied to a limited extent in SLE, and not at all in African SLE patients. We compared ANA in IC from Sudanese and Swedish SLE patients. We included 93 Sudanese and 332 Swedish SLE patients fulfilling the 1982 ACR criteria. IC were captured using C1q-coated beads. ANA specificities were quantified in sera and IC. Results were related to modified SLEDAI. Whereas serum levels of anti-Sm, anti-dsDNA and anti-ribosomal P were higher in Swedish patients, IC levels of most ANA specificities were higher among Sudanese patients. This difference was especially prominent for anti-chromatin antibodies, which remained after adjustment for age, disease duration and treatment. Total levels of C1q-binding IC correlated with levels of specific ANA in IC, with highest correlations for anti-chromatin antibodies among Sudanese patients. Whereas occurrence of anti- SSA/Ro60, anti-histone and anti-U1RNP in both serum and IC associated with high SLEDAI score, anti-dsDNA in IC but not in serum associated with high SLEDAI. ANA, especially antibodies targeting chromatin, accumulate more in IC from Sudanese SLE patients. If the autoantibody fraction forming IC is pathogenically important, this might explain the generally described severe SLE in black populations.

Background and objectives Immune complexes (IC) and autoantibodies against nuclear antigens are associated with systemic lupus erythematosus (SLE). Autoantibodies are suggested to have a pathogenetic impact by participating in IC formation. Few studies have however focused on studying autoantibody content in SLE IC, and the relative appearance of autoantibodies in IC versus in (IC-depleted) sera. By using polyethylene glycol (PEG) precipitation, we have studied how individual autoantibodies accumulate to different extents in SLE IC. PEG precipitation is however a crude technique by also precipitating other high molecular weight proteins. Here we have developed a technique to isolate pure IC from serum to enable detailed characterisation of autoantibody content individually in pure IC and IC-depleted serum. Material and methods IC in SLE sera were adsorbed to C1q-coated magnetic beads and thereafter eluted. Autoantibodies against dsDNA, Ro52, Ro60, SSB, Sm, Sm/RNP, ribosomal P antigen, histones and PCNA were determined by addressable laser bead immunoassay in serum, IC-depleted serum and purified IC. Circulating IC levels were determined by C1q binding. The levels of autoantibodies were normalised in relation to IgG levels. The C1q binding system was verified in real-time on a fully automated Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) system. Levels of autoantibodies in IC, IC-depleted serum and full serum were followed in five SLE patients during one year after treatment with anti-CD20 therapy. Results Adsorption of sera resulted in a 97.2%–99.5% reduction in circulating IC. QCM-D analyses showed the importance of each step in the adsorption/elution process. Serum samples and eluted IC showed different temporal patterns, and there were also strikingly different patterns between total amounts and concentrations related to total IgG levels in IC eluates. In some patients, anti-dsDNA levels and concentrations in IC eluates dropped sharply after anti-CD20 therapy whereas the corresponding levels for anti-Ro60/Ro52/SSB increased. All patients regained circulating B cells during the follow-up, and in at least 3/5 patients a transient or remaining increase in autoantibody concentration in eluted IC heralded the re-appearance of B cells. Conclusions We have developed a method to carefully quantify autoantibody content in circulating IC. Measurement of autoantibody amount and concentration in circulation SLE IC show individual temporal patterns that do not parallel serum autoantibody levels. Changes in autoantibody IC content/concentration might precede the re-occurrence of B-cells in rituximab-treated SLE patients.