Association of killer cell immunoglobulin‐like receptors with scleroderma

Abstract

Objective. Scleroderma is an autoimmune disorder of unknown etiology. A genetic contribution has been demonstrated, and genes influencing activation of the immune system have been potentially identified as candidate genes in this process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that are involved in the activation of T cells and natural killer cells is highly variable. Recently, an association of KIR2DS2 with vasculitis in patients with rheumatoid arthritis has been reported. Because scleroderma is characterized by an involvement of the vascular system, we sought to determine whether KIR2DS2 is associated with scleroderma.Methods. We typed 9 KIR genes in 102 patients with scleroderma and in 100 blood donors, using polymerase chain reaction on genomic DNA.Results. Twelve patients with scleroderma, compared with only 2 blood donors, had KIR phenotypes characterized by the presence of the activating KIR2DS2 and the absence of the corresponding inactivating KIR2DL2 (P ‫؍‬ 0.005).Conclusion. The genetic combination of KIR2DS2؉ and KIR2DL2؊ is associated with scleroderma.

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

“…[29][30][31][32][33][34][35] Our initial statistical analysis indicated a possible involvement of the activating KIR2DS2 and the inhibitory KIR2DL2 in the development of UC. Both genes displayed a high level of linkage disequilibrium with each other (previously reported in Hsu et al 39 ), occurring independently in only three of the samples genotyped in this study.…”

“…[29][30][31][32][33]35,38 Analysis revealed KIR2DL3 in the presence of HLA-C1 as the dominant association, significantly reduced in UC patients (P ¼ 0.019, odds ratio (OR) ¼ 0.577, 95% confidence interval (CI) ¼ 0.364-0.915), and the loss of significance with KIR2DL2 and -2DS2 (Figure 1). KIR2DL2 and -2DS2 in the presence of their shared ligand HLA-C1 also failed to reach significance (-2DL2/HLA-C1: OR ¼ 1.311, 95% CI ¼ 0.881-1.950; -2DS2/HLA-C1: OR ¼ 1.286, 95% CI ¼ 0.866-1.911).…”

“…Analysis of KIR/HLA ligand combination is increasingly of interest in the genetic study of inflammatory disorders, resulting in the discovery of KIR associations with psoriasis vulgaris, 29,30 psoriatic arthritis, 31 scleroderma, 32 rheumatoid arthritis 33 and type I diabetes. 34,35 In addition, celiac disease has been linked to 19q13.4, 36 where the KIR cluster is located, although genotype analysis of a limited number of KIR genes (KIR2DL1, -2DL2, -2DL3 and -2DL5) failed to detect an association.…”

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

“…This is supported by recent epidemiological observations that KIR/HLA compound genotypes with a supposedly activating profile (i.e., presence of activating KIR or lack of inhibitory KIRs or their respective ligands) are associated with resistance to HCV (5) and HIV infection (6), slower HIV disease progression (7), and better reproductive fitness (8). On the other hand, activating profiles enhance the risk for autoimmune disease such as psoriasis/psoriatic arthritis (9-13), type I diabetes (14), and scleroderma (15).…”

Células natural killer e vigilância imunológica

“…These results were analyzed and shown to be independent of patient age and disease stage. 36 The combination of BX donor and AA recipient was considered a risk factor for disease relapse (myeloid leukemia) and acute GVHD degrees II-IV. In a group of 112 transplanted patients, the incidence of acute GVHD was 46% in AA recipients with BX donors; 10% for AA recipients with AA donors; 20% for BX recipients with AA donors and 30% when both recipient and donor were BX.…”