POS0028 AN IMMUNOGENETIC STUDY OF CONTRASTING FORMS OF RHEUMATIC DISEASES; COEXISTING IN AN INDIVIDUAL PATIENT OR FIRST-DEGREE RELATIVES: AN OBSERVATIONAL PILOT STUDY
Authors: M. P. Shah, S. K. Upadhyaya, S. J. Gupta, R. Handa, D. Agarwal
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The co-existence of auto-immune arthritis (RA) with Autoinflammatory Spondylitis (SpA) in the same patient is uncommon; the reported prevalence is 1:10,000 to 1:50,000. This phenomenon of co-existence has never been studied from an immunogenetic perspective. Recent studies have identified that first-degree relatives of patients with RA are at a four-fold higher risk of developing symptoms of inflammatory arthritis compared to the healthy population. To the best of our knowledge, a study of phenotypic and genotypic features of patients with RA who have family members affected with Axial-SpA (AS), or vice versa, has never been studied and reported, either clinically or with regard to genetics. <h3>Objectives:</h3> To identify such First-Degree Relatives (FDRs) with a contrasting type of immune/autoinflammatory musculoskeletal disease (MSK) (group A), and to identify patients with co-existing RA with SpA (group B), and to study the MHC of both these groups. <h3>Methods:</h3> Patients aged ≥18 years with coexisting Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA) (fulfilling the ACR/EULAR criteria for RA and the ASAS criteria for SpA) were enrolled in the study over 12 months (September 2022 to September 23). Also, patients who had a first-degree relative with RA or SpA were enrolled as a separate cohort. Patients who had other types of arthritis such as enteropathic arthritis, psoriatic arthritis, other CTD-related arthritis, and pregnant women were excluded from the study. <h3>Results:</h3> The study groups A and B comprised 89 patients enrolled from a total of 3240 outpatients. 45 patients had coexisting RA and SpA (group B). The mean age and standard deviation of these patients was 41.38 ± 4.581 years. Among patients with an inflammatory/autoinflammatory musculoskeletal (MSK) disease (RA, SpA patients = 1988), approximately 1 in 54 patients had a family member afflicted with contrasting inflammatory arthritis (group A), a remarkably unexpected finding. Moreover, 1 in 44 had coexisting RA/SpA (group B). We studied the MHC by the NGS HLA technique (Illumina Miseq V2), of 28 patients with coexisting SpA/RA and of the 9 families who had 18 first-degree related members, affected with RA or SpA. The ratio of the frequencies of the study population to the control group (1029 healthy subjects, IndiGenomes, www.clingen.igib.res.in) was used to assess the over-expression of HLA alleles in our patient population. The most commonly found HLA alleles (top 5) studied at medium and low resolutions in both groups A and B are given in Table 1 below. Finally, the Odds ratio and p values were calculated (Table 2) for the top 5 HLA of the study group versus the control group (A and B groups). <h3>Conclusion:</h3> Co-existing RA/SpA in single patients or their unexpected presence among first-degree relatives, is more frequently seen than would be possible due to simple chance. Other than the usual HLA risk factors (*B27, *DR4, etc), HLA C*02 figures prominently in the disease groups, both in simple ratios and the Odd's Ratios. However, these HLA markers that have aggregated in families or single patients, may need to be studied in larger disease populations to see more robust associations. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>