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

Ralph D. Levinson, Tammy Martin, Lihui Luo, Elham Ashouri, James (Jim) Rosenbaum, Justine R. Smith, Carrie R. Austin, Joseph R. Lutt, Raja Rajalingam

Research output: Contribution to journalArticle

12 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 (US)
Pages (from-to)1505-1510
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

KIR Receptors
Anterior Uveitis
Spondylarthropathies
HLA-B27 Antigen
Odds Ratio
Natural Killer Cells
Ligands
Molecular Typing
DNA Fingerprinting
Gene Frequency
Genes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy. / Levinson, Ralph D.; Martin, Tammy; Luo, Lihui; Ashouri, Elham; Rosenbaum, James (Jim); Smith, Justine R.; Austin, Carrie R.; Lutt, Joseph R.; Rajalingam, Raja.

In: Investigative Ophthalmology and Visual Science, Vol. 51, No. 3, 03.2010, p. 1505-1510.

Research output: Contribution to journalArticle

Levinson, Ralph D. ; Martin, Tammy ; Luo, Lihui ; Ashouri, Elham ; Rosenbaum, James (Jim) ; Smith, Justine R. ; Austin, Carrie R. ; Lutt, Joseph R. ; Rajalingam, Raja. / Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy. In: Investigative Ophthalmology and Visual Science. 2010 ; Vol. 51, No. 3. pp. 1505-1510.
@article{3ce096f764cf45acb922336ba08a9012,
title = "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 [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.",
author = "Levinson, {Ralph D.} and Tammy Martin and Lihui Luo and Elham Ashouri and Rosenbaum, {James (Jim)} and Smith, {Justine R.} and Austin, {Carrie R.} and Lutt, {Joseph R.} and Raja Rajalingam",
year = "2010",
month = "3",
doi = "10.1167/iovs.09-4232",
language = "English (US)",
volume = "51",
pages = "1505--1510",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "3",

}

TY - JOUR

T1 - Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior uveitis, with and without axial spondyloarthropathy

AU - Levinson, Ralph D.

AU - Martin, Tammy

AU - Luo, Lihui

AU - Ashouri, Elham

AU - Rosenbaum, James (Jim)

AU - Smith, Justine R.

AU - Austin, Carrie R.

AU - Lutt, Joseph R.

AU - Rajalingam, Raja

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77949880530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949880530&partnerID=8YFLogxK

U2 - 10.1167/iovs.09-4232

DO - 10.1167/iovs.09-4232

M3 - Article

C2 - 19850842

AN - SCOPUS:77949880530

VL - 51

SP - 1505

EP - 1510

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 3

ER -