Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy

Ralph Levinson, Tammy Martin, Lihui Luo, Elham Ashouri, J Rosenbaum, Justine Smith, Carrie Austin, Joseph Lutt, Raja Rajalingam

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    Purpose. To determine associations between polymorphic genes that encode KIRs and their HLA class I ligands in patients with HLA-B27-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 [Pc] = 0.05; odds ratio [OR], 0.48; 95% CI, 0.25-0.90). The 3DL1+Bw4T80 combination implicated in weak inhibition was more frequent in subjects with AAU than in control subjects (P = 2.73 × 10-28, Pc = 8.2 × 10-27; OR, 13.5; 95% CI, 7.73-23.68). The 2DL1+HLA-C2 combination was decreased in subjects with axial SpA compared with subjects with AAU without axial SpA (P = 0.022; Pc = NS; OR, 0.43; 95% CI, 0.21-0.88). 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.

    Original languageEnglish
    Pages (from-to)1505-1510
    Number of pages6
    JournalInvestigative Ophthalmology & Visual Science
    Volume51
    Issue number3
    DOIs
    Publication statusPublished - Mar 2010

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