Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Killer-cell immunoglobulin-like receptors (KIRs) are activating and inhibitory receptors that regulate NK and NK-T cells, which have been found in psoriatic plaques and synovial fluid of patients with psoriatic disease (PsD). The inhibitory KIR3DL1 receptor binds to HLA-B alleles with the Bw4 motif. Binding of KIR3DL1 to HLA-Bw4 alleles with isoleucine at codon 80 (Bw4-80I) results in stronger inhibition than Bw4 alleles with threonine at codon 80 (Bw4-80T). KIR3DL1 alleles can be classified according to their expression levels on NK cells as High, Low, Null or KIR3DS1 (an activating allele of 3DL1). We examined the association of KIR3DL1 alleles and the Bw4 dimorphism with PsD.
Methods: Genomic DNA was available on 656 Caucasian patients with PsD (395 PsA patients: mean age 42 years, males 58%, age at psoriasis 28 years, age at PsA 36 years, PASI 5.6, active joint count 11, axial disease 33% who satisfied CASPAR criteria and 261 PsC patients: mean age 48 years, males 56%, age at psoriasis 30 years, PASI 5.4) and 377 Caucasian controls (mean age 41 years, males 48%). A nested quantitative PCR assay was designed to selectively amplify the KIR3DL1 locus and High, Low, Null, and KIR3DS1 alleles using custom Taqman SNP genotyping assays. DNA from the UCLA International KIR Exchange program was used for assay validation and optimization. Chi-squared test and tests for interaction were conducted and KIR3DL1 low and null allele categories were grouped together.
Results: The genotype frequencies across the 3 groups are given in Table 1. We observed statistically significant differences in the frequency of KIR3DL1 low/null alleles, and between Bw4-80I and -80T alleles. The frequencies of KIR3DL1 low/null alleles were lower in psoriatic disease and PsA compared to controls (Table 2). No significant differences between PsA and PsC could be demonstrated. We also investigated the interaction between KIR3DL1/3DS1 alleles and Bw4-80I and -80T and observed a trend towards significant interaction between KIR3DL1 low/null and Bw4-80T when comparing PsA to controls (p=0.1). The association between KIR3DL1 low/null was present only in the absence of Bw4-80T alleles (OR=0.86, 95% CI 0.78, 0.94, p=0.002).
Conclusion: In PsA patients, there was a significantly decreased expression of the KIR3DL1 Low/Null alleles particularly in the absence of HLA-B Bw4-80T. The results support the role of KIR genes and their interaction with HLA-B alleles in susceptibility to PsA.
Table 1. Differences in allele frequencies between the three groups.
|
Allele |
Controls (n=377) |
PsC (n=261) |
PsA (n=395) |
P value |
|
KIR3DL1 low/null |
225 (60%) |
140 (54%) |
199 (50%) |
0.03 |
|
KIR3DLI High |
194 (52%) |
126 (48%) |
199 (50%) |
0.73 |
|
KIR3DS1 |
126 (33%) |
98 (38%) |
150 (38%) |
0.37 |
|
HLA-B Bw4 |
233 (62%) |
177 (68%) |
292 (74%) |
0.002 |
|
HLA-B Bw4- 80I |
101 (27%) |
93 (36%) |
140 (35%) |
0.02 |
|
HLA-B Bw4- 80T |
151 (40%) |
102 (39%) |
191 (48%) |
0.02 |
Table 2. Association between KIR3DL1 low/null alleles and disease groups.
|
Comparison |
OR (95% CI) |
P value |
|
Psoriatic disease vs. controls |
0.72 (0.56, 0.93) |
0.01 |
|
PsA vs. controls |
0.69 (0.52, 0.91) |
0.01 |
|
PsC vs. controls |
0.78 (0.57, 1.08) |
0.13 |
|
PsA vs. PsC |
0.88 (0.64, 1.20) |
0.41 |
Disclosure:
R. Pollock,
None;
J. Berinstein,
None;
A. Thavaneswaran,
None;
F. Pellett,
None;
D. D. Gladman,
None;
V. Chandran,
None.
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