Killer Cell Immunoglobulin-like Receptors in HLA-B27a??Associated Acute Anterior Uveitis, with and without Axial Spondyloarthropathy

摘要

Purpose.: To determine associations between polymorphic genes that encode KIRs and their HLA class I ligands in patients with HLA-B27a??associated acute anterior uveitis (AAU), with and without axial spondyloarthropathy (axial SpA). Methods.: Molecular DNA typing methods were used to define the frequencies of variable KIR genes and their relevant HLA class I ligands in HLA-B27+ (B27+) Caucasian subjects with AAU and 429 healthy Caucasian control subjects. The patients were evaluated for axial SpA based on their histories using published criteria. Results.: Of 143 Caucasian subjects with AAU, 71 (49.6%) had features of axial SpA. The only difference between cases and controls in KIR gene frequencies was a trend toward fewer activating KIRs in subjects with AAU with axial SpA, which reached statistical significance for 2DS5 (P = 0.025, corrected P [P c] = 0.05; odds ratio [OR], 0.48; 95% CI, 0.25a??0.90). The 3DL1+Bw4T80 combination implicated in weak inhibition was more frequent in subjects with AAU than in control subjects (P = 2.73 ?? 10a??28, P c = 8.2 ?? 10a??27; OR, 13.5; 95% CI, 7.73a??23.68). The 2DL1+HLA-C2 combination was decreased in subjects with axial SpA compared with subjects with AAU without axial SpA (P = 0.022; P c = NS; OR, 0.43; 95% CI, 0.21a??0.88). Conclusions.: Evidence was found of a role for KIR-HLA combinations that trigger weaker inhibition in subjects with AAU. Furthermore, there was a trend toward fewer KIR3DS1, -2DS1, and -2DS5 in AAU patients with axial SpA, which have been implicated in NK cell activation. HLA-B27+ without KIR2DS3 (and -2DS1 and -3DS1) may fail to trigger an early NK cell response to clear antigenic stimuli, which may in part contribute to disease pathogenesis.