Distinct HLA-C/KIR Genotype Profile Associates with Guttate Psoriasis

Abstract

Psoriasis is a multifactorial disease with a strong genetic background. It associates strongly to HLA-Cw*0602. HLA-C interacts with killer immunoglobulin-like receptors (KIR) on natural killer (NK) and some natural killer-T (NKT) cells. KIR's function is triggered by specific binding to HLA ligands, which depends on the amino acid 80 of the MHC class I alpha-chain. This permits classifying all HLA-C alleles into two functional groups: asparagine (N80) or lysine (K80) carrying alleles. Psoriasis patients recruited at disease onset were categorized as guttate, vulgaris without arthropathy and vulgaris with arthropathy plus skin lesions. Patients and carefully matched controls were genotyped for position 80 of HLA-C and for KIR. Based on possible HLA/KIR combinations, individuals were classified according to expected NK/NKT cell responses: balanced (B), excess inhibition (EI), excess activation (EA), or undetermined (U). HLA-Cw6 and position 80 genotyping associated strongly to disease, whereas KIR2DS1 associated weakly. Individuals of the U and EI classes were more common among guttate psoriasis patients, which related to HLA-Cw*0602 status. These results suggest that different levels for NK/NKT cell activation thresholds, not only reduction, contribute to immune deregulation in psoriasis. In the guttate phenotype, balanced HLA-C/KIR interactions might be altered by the presence of concomitant streptococcal infections.

Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors

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Contribution of functional KIR3DL1 to ankylosing spondylitis

“…15,18,23,24 A number of studies has been conducted to identify possible associations between autoimmune conditions and KIR genes. [25][26][27][28][29][30][31][32][33][34][35] In particular, a number of works demonstrate 5 These authors contributed equally to this work. 16 Among the numerous KIR genes, the KIR3DL1/3DS1 locus is of particular interest with respect to AS because KIR3DL1 is the only KIR that recognizes HLA-B molecules of the Bw4 serotype, including HLA-B27.…”

Study of killer immunoglobulin-like receptor genes and human leukocyte antigens class I ligands in a Caucasian Brazilian population with Crohn's disease and ulcerative colitis

“…There is a growing interest about the possible role of KIR genes in several diseases, particularly those with alteration of the inflammatory response. A hypothesis is that various KIR/HLA combinations could produce differences in NK/NK T-cell activation [22,23].…”