POS0523 COULD ERAP POLYMORPHISMS IN HLA-B15 OR B27-POSITIVE PATIENTS WITH SPA INFLUENCE CYTOKINE PRODUCTION?
Authors: A. Santos Granados, N. Martínez Rodriguez, I. Rueda, G. Rodríguez Salas, C. Mesa Pedraza, S. Arias Correal, K. Orduz Uribe, E. Quintero-Muñoz, J. Bello Gualtero, J. Ballesteros Muñoz, E. Calvo, J. Londono Patiño
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The HLA-B27 allele has been associated with spondyloarthritis (SpA); however, in the Colombian population it is present in only 40% of patients, and HLA-B15 is present in almost 25%. A polygenic mechanism has been proposed to explain the development of SpA. Endoplasmic reticulum aminopeptidase (ERAP) genes 1 and 2 have been implicated. Additionally, the cytokine profile is different in the SpA subtypes. These allowed two models of disease, one with HLA-B27 and axial presentation and a second with HLA-B15 and peripheral presentation. <h3>Objectives:</h3> The aim was to determine the association between ERAP polymorphisms, cytokine profile, and patients with HLA-B27 or HLA-B15 positive SpA. <h3>Methods:</h3> 168 SpA patients were evaluated based on ASAS criteria, and HLA typing was performed via PCR technique. The polymorphisms were determined by the RT-PCR technique using Roche® probes for ERAP1 rs27044, rs17482078, rs10050860, and rs30187. For ERAP2, the probes used were rs2910686, rs2248374 and rs2549782. Human Cytokine/Chemokine Magnetic Bead Panel kit from Millipore (Human Th17MAG-14 Px25K) (Merck) determined the cytokine serum concentration. All reagents were provided with the kit and were prepared according to the manufacturer's recommendations. The allele and genotype frequencies polymorphisms were obtained by direct counting. In each group, the Hardy-Weinberg equilibrium was evaluated using the 2 test. The haplotypes were constructed and analyzed using Haploview v.4.2. Associations were assessed using odds ratio (OR). Stata v.17.0 program was used to analyze data. PCA used PRISMA 10 program. <h3>Results:</h3> 111 patients were HLA-B27, and 57 were HLA-B15. 63 (37.5%) were women, and 105 (62.5%) were men. In the association test we identified sixteen haplotypes, of which three associated significantly with protection (CCCCCAC, GTCCCAC, GTTTTAC; p&lt;0.005) and one risk haplotype [GTCCTGC; 4.272(1.565-11.655), p&lt;0.005] were described in Figure 1. Through the analysis of the Pearson Correlation Coefficient (PCC) and the Principal Component Analysis (PCA), we detected a profile of variables that characterize the HLA-B15 group, which were spinal pain, elderly, arthritis as first symptom in onset disease, more peripheral manifestations, polymorphism rs10050860, and rs30187, highest IL9, IL10, IL12, IL13, IL15, IL17f, IL21, IL22, IL23, IL28a, IL33, TNFβ, GM-CSF. The variables that characterized the HLA-B27 group were higher correlation with men, axial, lumbar pain, poor BASFI, BASDAI, polymorphism rs10050860 and rs30187, highest IL22, IL23, IL25, IL31, IL33 (Figure 2). <h3>Conclusion:</h3> In the population analyzed, we found a characteristic profile of SpA presentation that could be determined by the HLA-B15 or B27 allele, ERAP inheritance patterns, and cytokine concentrations. This could suggest the influence of ERAP on the profile of secreted cytokines in these patients and their clinical presentation. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>