Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy.
OBJECTIVE
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.
Ocular Inflammatory Disease Center, Jules Stein Eye Institute, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California, USA.
Ralph D
RD
Levinson
Tammy M
TM
Martin
Lihui
L
Luo
Elham
E
Ashouri
James T
JT
Rosenbaum
Justine R
JR
Smith
Carrie R
CR
Austin
Joseph R
JR
Lutt
Raja
R
Rajalingam
D000208:Acute Disease; D016172:DNA Fingerprinting; D020224:Expressed Sequence Tags; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics*; D025242:Spondylarthropathies / Q000235:genetics*; D014606:Uveitis, Anterior / Q000235:genetics*
D015796:HLA-B27 Antigen; D054340:Receptors, KIR