Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4.

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region.

Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus.

Objective: In the sanroque mouse model of lupus, pathologic germinal centers (GCs) arise due to increased numbers of follicular helper T (Tfh) cells, resulting in high-affinity anti-double-stranded DNA antibodies that cause end-organ inflammation, such as glomerulonephritis. The purpose of this study was to examine the hypothesis that this pathway could account for a subset of patients with systemic lupus erythematosus (SLE).

Methods: An expansion of Tfh cells is a causal, and therefore consistent, component of the sanroque mouse phenotype.

Association of the co-stimulator OX40L with systemic lupus erythematosus.

The archetypal systemic autoimmune disease systemic lupus erythematosus (SLE) has incompletely understood pathogenesis, although evidence suggests a strong genetic component. Unlike organ-specific autoimmune diseases such as type 1 diabetes, the genetics of lupus are not as dominated by the effect of a single locus. Undoubtedly, the major histocompatibility complex is the greatest and most consistent genetic risk factor in SLE susceptibility; however, recent candidate gene and whole genome association (WGA) studies have identified several other genes that are likely to advance our understanding of this complex disease.

Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem complex autoimmune disease of uncertain etiology (OMIM 152700). Over recent years a genetic component to SLE susceptibility has been established. Recent successes with association studies in SLE have identified genes including IRF5 (refs.

Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation.

Results from two studies have implicated the interferon regulatory gene IRF5 as a susceptibility gene in systemic lupus erythematosus (SLE). In this study, we conducted a family-based association analysis in 380 UK SLE nuclear families. Using a higher density of markers than has hitherto been screened, we show that there is association with two SNPs in the first intron, rs2004640 (P = 3.

The innate immune responses of colonic epithelial cells to Trichuris muris are similar in mouse strains that develop a type 1 or type 2 adaptive immune response.

Trichuris muris resides in intimate contact with its host, burrowing within cecal epithelial cells. However, whether the enterocyte itself responds innately to T. muris is unknown.