Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


MICA016 Allele Differentiates Skin and Joint Manifestations of Psoriatic Disease.

Chandran3,  Vinod, Pollock3,  Remy, Barrett1,  Jessica, Eder3,  Lihi, Pellett3,  Fawnda, Yao3,  Christopher, Lino3,  Marsel

MRC Biostatistics Unit, University of Cambridge Institute of Public Health, Cambridge, UK
Toronto Western Hospital, Toronto, ON, Canada
University of Toronto Psoriatic Arthritis Clinic, Toronto Western Hospital

Background:

The Major Histocompatibility Complex Class 1 Chain-Related Gene A (MICA) is a multiallelic locus in the MHC region that encodes a 43 kDa cell-surface protein that functions to activate pathways in innate and adaptive immunity. Previous studies have shown associations between psoriatic arthritis (PsA) and MICA-A9 corresponding to MICA*00201 and MICA*017, and MICA-A4, corresponding to MICA*001, MICA*00701, and MICA*018, when compared to healthy controls. However, it is not clear whether the associations are with psoriasis or with PsA, and if the associations are independent of HLA alleles. Our purpose was to delineate the contributions of MICA alleles to susceptibility to skin and joint manifestations of psoriatic disease.

Methods:

249 unrelated Caucasian subjects with PsA (96 females, mean age 41 years, PsA duration 7 years, psoriasis duration 14 years, actively inflamed joint count 10, PASI score 5.3), 243 with psoriasis (100 females, mean age 47 years, psoriasis duration 17 years, PASI score 5) and 248 healthy controls (141 females, mean age 49 years) were recruited for this study. Genotyping for 55 MICA alleles was done by PCR-SSP and for HLA-B, and -C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and univariate and multivariate logistic regressions performed, adjusting for HLA-B and C alleles previously shown to be associated with psoriasis and/or PsA.

Results:

In univariate analyses MICA*00201/020, MICA*016 frequencies were significantly increased in psoriatic disease (PsA and psoriasis combined) compared to controls, while MICA*00801, MICA*018 and MICA*049 frequencies were decreased. MICA*00201/020 and MICA*00701/026 were increased in PsA compared to controls and MICA*004, MICA*00801 and MICA*018 were decreased. MICA*00201/020, MICA*016 and MICA*017 frequencies were significantly increased in psoriasis compared to controls, while MICA*00801 was decreased. Finally, MICA*00701/026 was increased in PsA compared to psoriasis, and MICA*016 was decreased. There was a significant effect of homozygosity for the allele MICA*00801. Results of the multivariate analyses are provided in the table.

Table. Results of multivariate logistic regression analyses using MICA alleles found significant in the univariate analyses as explanatory variables, as well as the results after the inclusion of HLA alleles that were found to be at least marginally significant in univariate analyses.

   After Adjustment for HLA
AlleleORP ValueORP Value
Psoriatic Disease vs. Controls    
MICA*00201/0201.6940.0121.5050.078
MICA*008010.6860.030.7880.211
MICA*0163.0220.0443.6280.021
MICA*0180.4510.0170.4940.041
MICA*0490.1260.060.1760.115
PsA vs. Controls    
MICA*00201/0201.8240.0141.4620.174
MICA*0040.5280.0280.6810.204
MICA*00701/0262.6020.0020.3330.115
MICA*008010.7640.2090.8460.480
MICA*0180.4370.0510.4480.067
Psoriasis vs. Controls    
MICA*00201/0201.8360.0111.4730.135
MICA*008010.6860.0620.6380.036
MICA*0164.4610.0094.3880.011
MICA*0171.8750.0191.2180.619
PsA vs. Psoriasis    
MICA*00701/0265.074<0.0011.0260.969
MICA*00801†1.1730.4491.2940.265
MICA*0160.6080.2430.5970.245

After adjusting for HLA-B*13, -27, -38, -57 and HLA-Cw*01, -02, -06, -12 alleles, no MICA alleles were associated with PsA, but MICA*016 remained significantly associated with psoriasis [Odds Ratio (OR) = 4.4, p = 0.011] and MICA*00801 remained protective [OR = 0.69, p = 0.036]. MICA*00801 homozygosity significantly increased susceptibility to PsA for patients with psoriasis.

Conclusions:

MICA allele associations with psoriasis and PsA are dependent on linkage disequilibrium with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 and MICA*00801 influence the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA.

To cite this abstract, please use the following information:
Chandran, Vinod, Pollock, Remy, Barrett, Jessica, Eder, Lihi, Pellett, Fawnda, Yao, Christopher, et al; MICA016 Allele Differentiates Skin and Joint Manifestations of Psoriatic Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1979
DOI: 10.1002/art.29744

Abstract Supplement

Meeting Menu

2010 ACR/ARHP