AB0418 AN IMMUNOGENETIC STUDY OF AN INDIAN COHORT OF PSORIATIC ARTHRITIS PATIENTS WITH REFERENCE TO THEIR PHENOTYPE (2024)

Abstract

Background: Genetic factors, especially the major histocompatibility complex (MHC) play a significant role in susceptibility and expression of Psoriatic arthritis (PsA). To the best of our knowledge, no data regarding the genotype-phenotype association in PsA patients has been reported from the Indian Subcontinent.

Objectives: To study the Human Leucocyte Antigen (HLA) class I and II in PsA patients, and analyse the influence of HLA alleles on the clinical expression.

Methods: Consenting consecutive PsA patients, as per the CASPAR criteria, were enrolled in this pilot study over 12 months (August 2022 to August 2023). Patients were clinically phenotyped into 4 groups, namely Rheumatoid Arthritis-like (RA-like), Ankylosing Spondylitis-like (AS-like), Peripheral Spondyloarthritis-like (pSpA-like) and Hand Osteoarthritis-like (OA-like). We studied the HLA by the Next Generation Sequencing HLA technique (Illumina Miseq V2). HLA data for the control population (n=1029 healthy Indians) was obtained from IndiGenomes (https:/clingen.igib.res.in/HLA/). The allele frequency was compared between cases and controls. For genotype and phenotype association, data analysis was done using SPSSv23 and appropriate statistical tests were applied.

Results: 43 PsA patients were included; mean age was 43.81±11.58 years and the male: female ratio was 1.05:1. The mean disease duration was 5.3±4.5 years. Fifteen patients (34.8%) had a positive family history of psoriasis or inflammatory arthritis. Our cohort had a higher frequency of HLA-A*02 (20.9% vs 12%), HLA-B*27 (13.9% vs 2.2%), HLA-C*02 (10.4% vs 1.5%) and HLA-C*06 (20.9% vs 9.5%) when compared to the healthy population (Table 1). Evaluating for possible associations between the alleles and disease phenotypes, an expected association of HLA-B*27 was found with the AS-like phenotype (OR=10.4, p= 0.002). The HLA-B*27:05 subtype was most frequent. HLA-A*02 and HLA-C*02 were also present at a higher frequency (OR=7.58, p= 0.009 and OR=7.71, p=0.014 respectively). None of our patients had the HLA-B*07 allele. On the contrary, HLA-C*06 appeared to be protective (OR= 0.08, p=0.014). The occurrence of uveitis and nail changes were statistically higher in this phenotype. A positive trend of HLA-DR4 was seen in the RA-like cohort, however this was not statistically significant (OR=3.5, p= 0.166). HLA-A*01 had a significantly higher frequency among patients with pSpA-like phenotype (OR=5.37, p=0.034) as opposed to the RA-like phenotype where it appeared to be protective (OR=0.21, p=0.018). This phenotype also showed a higher frequency of HLA-B*37 (OR= 13.71, p=0.034). HLA-B*37 positivity was seen with HLA-C*06 positivity, raising the possibility of linkage disequilibrium. There was a trend of HLA-B*52 positivity in patients with OA-like phenotype (p=0.037). (Table 2)

Conclusion: From the Indian subcontinent, ours is the first study to analyze the HLA haplotype of PsA patients and look for the influence of HLA alleles on the clinical expression of the disease. Consistent with existing global literature, our study shows an association of HLA-A*02, HLA-B*27, HLA-C*06 with increased susceptibility to PsA. Also, a significant association of HLA-C*02 with PsA susceptibility has been found. Our study identifies HLA-A*02 and HLA-C*02 as possible markers for axial disease in addition to the well-established HLA-B*27; and HLA-A*01 and HLA-B*37 for oligoarthritis. Our data highlights the need for functional genomics to improve our understanding of the role played by genotype in the phenotypic expression of PsA. The findings from our pilot study need to be validated in larger cohorts.

Acknowledgements: Delhi Rheumatology Association.

Disclosure of Interests: None declared.