P171 Clinical and genetic profiling of first-degree relatives of Human Leukocyte Antigen-B*27-positive spondyloarthritis patients

Background/Aims Spondyloarthritis (SpA), a HLA-B*27-linked disease, affects 0.7-1.0 per 1,000 in India, 0.2-0.5% globally, with their first-degree relatives (FDRs) at a 20-27% lifetime risk if B*27 positive. Although clinical features are reported in FDRs, preclinical factors contributing to SpA are lacking. This study evaluates the association of HLA-B*27 and ERAP1 polymorphisms with clinical features in FDRs. Methods This is a cross-sectional study from JIPMER, a tertiary centre in South India. A total of 180 patients fulfilling ASAS classification criteria for SpA and 200 FDRs were recruited. Genotyping of HLA-B*27 and ERAP1 genes rs27037, rs27044, rs30187, rs26618, rs26653, and rs3734016, was done using ARMS-PCR and TaqMan allelic discrimination assays, respectively. Demographics, disease activity, and functional indices (BASDAI, BASFI, BASMI, ASDAS-CRP) were collected. Results All SpA patients were positive for HLA-B*27, while its 56% (n = 112) in FDRs. Among FDRs with clinical symptoms (n = 32; 16%), B*27 positivity was 75% (n = 24), pure axial disease was 40.6% (n = 13), and both axial and peripheral disease was 59.4% (n = 19). As per ASDAS-CRP, 62.5% (n = 20) symptomatic FDRs had inactive/low and 37.5%(n = 12) had high/very high disease activity. Distribution of ERAP1 polymorphisms was similar in SpA classified based on age (early vs late), family history, and peripheral disease. GT and CG genotypes of rs27037 (Pc = 0.038; OR = 2.03) and rs27044 (Pc = 0.045; OR = 1.97) respectively, were associated with lower disease activity in SpA. Comparing FDRs with and without clinical symptoms, we noted that rs30187 CT (Pc = 0.049; OR = 2.35) and rs3734016 AG genotypes (Pc = 0.002; OR = 4.32) and their G allele (Pc = 0.001; OR = 4.08) were more frequent among those with symptoms. Upon classifying FDRs based on their B*27 status, an association of the G allele of rs26653 with B*27 positivity was noted but was not statistically significant (Pc = 0.057). Demographic, clinical and genetic data are given in Table 1. Conclusion This first Indian familial study shows that ERAP1 polymorphisms might play a dual role by modulating severity in established SpA and influencing early manifestations in at-risk FDRs. Longitudinal follow-up of FDRs to record evolution and functional studies to understand the epistatic interactions between HLA-B*27 and ERAP1 are warranted for insights into pre-symptomatic risk identification. Disclosure V. Koneru: None. C.M. Mariaselvam: None. G. Abhilash: None. S. Philip: None. R. Khadar: None. C. Kg: None. M.M. Thabah: None. V.S. Negi: None.