No abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. The tumour necrosis factor (TNF) superfamily of genes play a central role in immune regulation and have been proposed to be involved in the development of SLE. TNFRSF5 (CD40) falls on 20q11 -13, a region linked with SLE in three independent genome-wide studies. TNFSF5 (CD40L) falls on Xq26 and is the ligand for TNFRSF5. Seven single-nucleotide polymorphisms (SNPs) in CD40 and eight SNPs in CD40L were looked at for linkage disequilibrium (LD) and haplotype analysis in EuropeanCaucasians. Limited haplotype diversity was observed across CD40 and CD40L, and 497% of the diversity was captured. We also examined the association of SNPs and haplotypes in CD40 and CD40L with SLE in European-Caucasians. There was no evidence of association for CD40 or CD40L in 408 European-Caucasian families with SLE from UK. Haplotype tagging SNPs (htSNPs) are made known, which will facilitate analysis for susceptibility in other autoimmune diseases and risk for infectious disease.

Objective. To determine whether key features of systemic lupus erythematosus (SLE), namely, production of non-nuclear antibodies (anti-C1q and anticardiolipin antibodies [aCL]) and depletion of complement components C3 and C4, aggregate in families. In addition, we examined relationships between anti-C1q and C3 and C4 levels.Methods. The study cohort comprised 1,037 predominantly white (82%) nuclear families in which at least 1 member had SLE. Associations of antibody measurements between probands and their unaffected siblings were examined using parametric and nonparametric analyses, along with associations between unaffected siblings and their parents. The heritability of anti-C1q, C3, and C4 was estimated, and interdependencies between these factors were examined in a regression model accounting for the family structure of the data set.Results We also demonstrated significant heritability of anti-C1q, C3, and C4 (ϳ45%). Anti-C1q was negatively associated with C3 and C4 in SLE probands but not in their healthy relatives.Conclusion. Non-nuclear antibodies and C3 and C4 cluster within the families of SLE probands, suggesting that specific autoantibody formation is partly genetically determined, even if the total genetic effect in unaffected relatives is insufficient to cause disease. Anti-C1q antibodies accelerate C3 and C4 depletion in patients with SLE but have no effect in the absence of disease.Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by immune-mediated damage to multiple organ systems. Studies have shown a concordance rate of 24-57% in monozygotic twins compared with 2-5% in dizygotic twins and a sibling risk ratio ( s ) of 20-29 (1-4). There is, therefore, evidence for a strong genetic component to SLE, although the overall etiology is likely to depend on a complex interaction of genetic and environmental factors.The classic autoantibodies in patients with SLE are those directed at nuclear antigens; however, antibodies directed against non-nuclear targets also play an Drs.