The MICA‐A4 triplet repeats polymorphism in the transmembrane region confers additional risk for development of psoriatic arthritis in the Croatian population

Abstract

The aim of this study was to investigate possible differences in the frequencies of alleles at the HLA loci and at microsatellite loci within the HLA region among patients suffering from psoriatic arthritis (PsA) and healthy controls. Fifty-eight Croatian PsA patients (28 male and 30 female) and 157 healthy unrelated controls were typed for HLA alleles (A, B, Cw and DRB1) by the polymerase chain reaction-sequence-specific primers (PCR-SSP) method, while microsatellite alleles (D6S265, D6S273, MHC class I chain-related gene (MICA) and MIB) were analysed by electrophoresis in an ALFexpress sequencer (Pharmacia Biotech, Uppsala, Sweden). The findings from this study were: (1) the frequencies of B*39 and B*57 were significantly increased in PsA patients; (2) differences in the frequencies of B*13 and B*27 were not statistically significant after correction; (3) the B*0702, B*18, and B*38 alleles were decreased in patients only before correction; (4) none of the alleles at other HLA loci tested were associated with PsA in Croatia; (5) polymorphism at D6S265, D6S273, and MIB microsatellites in patients did not show any statistically significant differences when compared to controls; (6) the increase in the MICA-A4 allele frequency in PsA patients was independent of the B*39 and B*57 alleles.

Psoriasis: skin and joints, same fight?

“…This allele is associated above all with polyarticular forms (relative risk 9.3 vs. 3.2 for all psoriatic arthritis cases) 38 . In another study, a correlation with MIC‐A‐A9 was not found, but instead, in this Croatian population, a correlation with MIC‐A‐A4 ; 39 A polymorphism of the TNF genes ( TNFα‐308 and TNFβ‐252 (A)) has been observed in peripheral psoriatic arthritis 24,40–42 . This is interesting because the polymorphism of TNFα‐30 8 is associated with elevated levels of TNF‐α 40,43 .…”

Pathogenesis of psoriatic arthritis

“…In a Spanish study of 120 PsA patients, 50 psoriasis patients and 175 healthy control subjects, Cw6 was associated with psoriasis but not PsA. In a Croatian population of 58 PsA patients and 157 healthy control subjects, development of PsA was associated with the MICA-A4 (p c = 0.017), but not the previously identified MICA-A9 triplet [17]. In a Croatian population of 58 PsA patients and 157 healthy control subjects, development of PsA was associated with the MICA-A4 (p c = 0.017), but not the previously identified MICA-A9 triplet [17].…”

Predisposition to idiopathic thrombocytopenic purpura maps close to the major histocompatibility complex class I chain-related gene A

“…However, polymorphisms on STR-MICA may be immunologically relevant, because they have been associated with autoimmune dysfunctions like BehÈet's disease and psoriatic arthritis [15,34]. In the context of its immunological function, the MICA gene itself was described as a ligand for the NKG2D/DAP10 stimulatory receptor complex [35], expressed on natural killer cells, gd T cells and CD8 ϩ ab T cells, triggering cytolysis mediated by NKG2D-bearing cells [36] and also costimulating CD8 ϩ ab T lymphocytes [37].…”