Abstract

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.

Highlights

  • Abbreviations according to the revised (ACR) American College of Rheumatology anti-nuclear autoantibodies (ANA) Anti-nuclear associated antibodies C1q-binding IC (CIC) C1q-binding immune complexes DMARDS Disease-modifying anti-rheumatic drugs DsDNA Double stranded DNA IC Immune complexes proliferating cell nuclear antigen (PCNA) Proliferating cell nuclear antigen SLE Systemic lupus erythematosus Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Systemic lupus erythematosus disease activity index

  • Sudanese patients had lower serum levels than Swedish patients of anti-Sm, antidsDNA (14.0/6.0–110.5 vs. 28.0/11.0–166.0; p = 0.001) and anti-ribosomal P antigen (1.0/1.0–3.0 vs. 2.0/1.0–5.0; p = 0.0006). This situation was completely reversed for levels of specific ANA in solubilized IC from the same serum samples; levels of all antibodies except anti-SSA/Ro52 and anti-SSA/Ro60 were higher in IC from Sudanese than from Swedish patients

  • This difference was highly significant for most ANA specificities, with more than twofold difference in median levels of anti-chromatin antibodies detected in IC from Sudanese patients, Table 2 and Fig. 1

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Summary

Introduction

Abbreviations ACR American College of Rheumatology ANA Anti-nuclear associated antibodies CIC C1q-binding immune complexes DMARDS Disease-modifying anti-rheumatic drugs DsDNA Double stranded DNA IC Immune complexes PCNA Proliferating cell nuclear antigen SLE Systemic lupus erythematosus SLEDAI Systemic lupus erythematosus disease activity index. Systemic lupus erythematosus (SLE) is an immune complex-mediated inflammatory condition with anti-nuclear autoantibodies (ANA) against nuclear-associated antigens. Immune complexes (IC) are formed by non-covalent binding of antibodies and corresponding antigen with or without the presence of complement proteins. Other techniques were developed and modified to detect specific antigens like DNA or complement fragments contained in IC. In our recently published paper comparing SLE in Sudan and Sweden, we have reported increased prevalence of anti-Sm antibodies with higher organ damage, markedly shorter disease duration and younger age among Sudanese patients suggesting reduced survival in that ­population[17]. Quantification of ANA in IC and association to SLE has not been studied in African populations, and previous studies showing association with disease activity involved mainly non-African e­ thnicities[7,18]

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