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

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 [P(c)] = 0.05; odds ratio [OR], 0.48; 95% CI, 0.25-0.90). The 3DL1+Bw4(T80) combination implicated in weak inhibition was more frequent in subjects with AAU than in control subjects (P = 2.73 x 10(-28), P(c) = 8.2 x 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; P(c) = 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.

• Authors: Ralph D Levinson, Tammy M Martin, Lihui Luo, Elham Ashouri, James T Rosenbaum, Justine R Smith, Carrie R Austin, Joseph R Lutt, Raja Rajalingam
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 51 Issue 3 Pg. 1505-10 (Mar 2010) ISSN: 1552-5783 [Electronic] United States
• PMID: 19850842 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-B27 Antigen
• Receptors, KIR

Topics

• Acute Disease
• DNA Fingerprinting
• Expressed Sequence Tags
• Female
• Gene Frequency
• Genotype
• HLA-B27 Antigen (genetics)
• Humans
• Male
• Polymerase Chain Reaction
• Receptors, KIR (genetics)
• Spondylarthropathies (genetics)
• Uveitis, Anterior (genetics)