POS1090 BEYOND HLA-B27: EVALUATING THE GENETIC DIVERSITY OF HLA-B ALLELES IN BRAZILIAN BONE MARROW DONORS
Authors: G. Resende, C. Saad, C. Marques, D. Oliveira, J. S. Bueno Filho, P. D. Sampaio-Barros, M. Pinheiro
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Spondyloarthritis (SpA) has been classified as an 'MHC-I-opathy,' with HLA-B27 recognized as a major genetic factor half a century ago [1]. Additionally, other MHC-I alleles, including HLA-B7, B35, B38, and B40 (B60/B61), have been implicated in increasing the risk of SpA [2-4]. A recent publication from our group showed an overall HLA-B27 positivity rate of 4.35% in Brazilian healthy people [5]. <h3>Objectives:</h3> To evaluate each allelic frequency (AF) of HLA-B and to assess whether the frequencies of genotypes (GF) containing HLA-B27 in heterozygosis adhere to Hardy–Weinberg equilibrium (HWE) in a substantial sample of healthy individuals in Brazil. <h3>Methods:</h3> Using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database, this cross-sectional ecological study analyzed the multiallelic HLA-B site in healthy donors aged 18 to 60 years. HWE was checked by chi-square test of independence. <h3>Results:</h3> Between 1994 and 2022, 5,389,143 healthy individuals were included in REDOME. In addition to HLA-B27, other 34 different alleles were identified. Table 1 presents the AF of each HLA-B, along with the expected and observed GF. Approximately half of the observed genotypes (15 out of 34) adhered to HWE, while the remaining 19 did not. Figure 1 shows the difference in observed from expect GF. <h3>Conclusion:</h3> The noncompliance with HWE equilibrium in this sizeable and diverse sample of healthy individuals may be explained by the extensive miscegenation within the Brazilian genetic background, shaped by colonization and internal migratory flows. Further investigations involving Brazilian SpA patients are essential to elucidate the potential implications of these findings on the prevalence and phenotype features of SpA in Brazil. <h3>REFERENCES:</h3> [1] Kuiper JJ, Prinz JC, Stratikos E, Kuśnierczyk P, Arakawa A, Springer S, et al. EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders. Ann Rheum Dis. 2023;82(7):887-96. [2] Laza IM, Ventades NG, Hervella M, de-la-Rúa C. Contribution of ancient human remains analysis to the understanding of the variability in HLA-B gene variants in relation to the diagnosis of spondyloarthropathies. J Autoimmun. 2018; 94:70-82. [3] Reveille JD, Zhou X, Lee M, Weisman MH, Yi L, Gensler LS, et al. HLA class I and II alleles in susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2019;78(1):66-73. [4] Wu X, Wu J, Li X, Wei Q, Lv Q, Zhang P, et al. The Clinical Characteristics of Other HLA-B Types in Chinese Ankylosing Spondylitis Patients. Front Med (Lausanne). 2020; 7:568790. [5] Resende GG, Saad CGS, de Oliveira DCM, de Sousa Bueno Filho JS, Sampaio-Barros PD, de Medeiros Pinheiro M. HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil. Adv Rheumatol. 2023;63(1):16. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>