Objective Genetic studies in the systemic sclerosis (SSc), an autoimmune disease that clinically manifests with dermal and internal organ fibrosis and small vessel vasculopathy, have identified multiple susceptibility genes including HLA-class II, PTPN22, IRF5, and STAT4 which have also been associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE). These data suggest that there are common autoimmune disease susceptibility genes. The current report sought to determine if polymorphisms in the C8orf13-BLK region (chromosome 8p23.1-B lymphoid tyrosine kinase), which is associated with SLE, are associated also with SSc. Methods Two variants in the C8orf13-BLK region (rs13277113 & rs2736340) were tested for association with 1050 SSc cases and 694 controls of North Americans of European descent and replicated in a second series 589 SSc cases and 722 controls from Spain. Results The “T” allele at rs2736340 variant was associated with SSc in both the U.S. and Spanish case-control series (P=6.8×10−5, OR 1.27, 95%CI 1.1–1.4). The “A” allele at rs13277113 variant was associated with SSc in the U.S. series only (P=3.6×10−4, OR 1.32, 95%CI 1.1–1.6) and was significant in the combined analyses of the two series (P=2.0×10−3; OR 1.20, 95%CI 1.1–1.3). Both variants demonstrated an association with the anti-centromere antibody (P=2.2×10−6 and P=5.5×10−4, respectively) and limited SSc (P=3.3×10−5 and P=2.9×10−3, respectively) in the combined analysis. Peripheral blood gene expression profiles suggest that B-cell receptor and NFκB signaling are dysregulated based on the risk haplotype of these variants. Conclusion We identify and replicate the association of the C8orf13-BLK region as a novel susceptibility factor for SSc, placing it in the category of common autoimmune disease susceptibility genes.

In patients with RA, chronic inflammation and its suppression during anti-TNF therapy have limited influence on plasma leptin concentrations, while significantly decreasing circulating adiponectin levels. Our findings question the suggested key role of inflammatory markers in regulating adipocytokine patterns in RA.

Over the last years microarray technologies have generated new perspectives for the high-throughput analysis of biological systems. Nowadays, it is possible to monitor thousands of genes in a single experiment. This molecular profiling technology combined with standardised and validated clinical measurements can allow a more precise characterisation of a patient's phenotype, and may lead to the design of therapeutic protocols and procedures better tailored to an individual patient's needs. In this report we provide an overview of expression profiling studies in rheumatoid arthritis (RA). RA is a chronic inflammatory disease in which both genetic and environmental factors are involved. The precise molecular mechanisms underlying RA are not fully understood. A systematic literature search revealed nine array-based expression profiling studies in patients with RA. Findings from these studies were compared with those of linkage and genome-wide association (GWA) studies. Although we observed many differences in study design, analysis and interpretation of results between the different studies, we extracted two sets of genes: (1) those differentially expressed in more than one study, and (2) genes differentially expressed in at least one of the reviewed studies and present in RA linkage or GWA loci. We suggest that both sets of genes include interesting candidate genes for further study in RA.

Despite its demonstrated functionality, the 676T>G polymorphism in the TNFSF1b gene does not have a major role in either the response to anti-TNF therapy or in the disease severity or radiological progression in RA.

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