Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
The human leukocyte antigen (HLA)-DRB1 with alleles that contain common amino acid motif QKRAA termed shared epitope (SE) confer the major locus of genetic susceptibility to rheumatoid arthritis (RA). Molecular basis of tolerance loss marked by autoantibody production remains to be resolved. The aim of this study was to analyse an association between survivin, oncoprotein recently reported to be associated with early bone damage and poor therapy response, HLA-DRB1 SE alleles and antibodies to citrullinated peptides (ACPA) in Malaysian patients.
Methods: : 1233 RA patients and 1566 age, sex and ethnically matched healthy controls of the Malaysian Epidemiological Investigation of rheumatoid arthritis (MyEIRA) study group were included in the study. The levels of survivin, ACPA and rheumatoid factor were measured by specific and standardized ELISAs. HLA-DRB1 genotyping was performed by the PCR-SSO method. Among the HLA-DRB1 alleles, DRB1*01, DRB1*0401, DRB1*0404, DRB1*0405, DRB1*0408, DRB1*0410, and DRB1*10 were defined as SE alleles. The odds ratio (OR[95%CI]) and relative risk (RR) of developing ACPA-positive and ACPA-negative RA was calculated for survivin and the presence of any SE allele. Potential interaction between survivin and HLA-DRB1 SE alleles was also calculated.
Results: The prevalence of survivin-positivity among RA patients was 50.7%, compared to 5.4% in healthy controls (p=2.66E-164) with a significantly higher prevalence in the Indian ethnic population compared to the Malay and Chinese (p<0.0001). Survivin-positivity was associated with an increased risk of developing ACPA-positive RA (OR 33.5[25.8-43.6]) and ACPA-negative RA (OR 5.3[3.9-7.2]), both p<0.0001. The survivin-positivity was associated with SE-alleles in 23.6% of RA patients and the majority of patients combining survivin and SE (91%) were also ACPA–positive. The combination of survivin-positivity and SE increased the risk of ACPA-positive RA 19 folds.
Conclusion: The survivin-positivity increases risk of the development of ACPA-positive and ACPA-negative RA. Combination of survivin-positivity, SE and APCA has a strong additive effect for the risk of RA in the population from Malaysia.
C. L. Too,
J. S. Dhaliwal,
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