Aspartic acid70 in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans

Luis Francisco Valdés-Corona; Susana Hernández-Doño; Tatiana Sofia Rodríguez-Reyna; Rafael García-Silva; Juan Jakez; Monica Escamilla-Tilch; Guadalupe Lima; Luis Llorente; Carlos Pineda; Edmond Yunis; Julio Granados

doi:10.1016/j.jtauto.2020.100057

Aspartic acid⁷⁰ in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans

J Transl Autoimmun. 2020 May 15:3:100057. doi: 10.1016/j.jtauto.2020.100057. eCollection 2020.

Affiliations

¹ Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico.
² Immunogenetics Division, Transplant Department. Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico.
³ Centro Medico 20 de Noviembre, ISSSTE, Mexico.
⁴ Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico.
⁵ Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, USA.

Abstract

Introduction: Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers.

Methods: High-resolution HLA class II typing was performed using a sequence-based method.

Results: The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC = 0.021, OR = 2.4, 95%CI = 1.19-4.75 and pC = 0.009, OR = 3.4, 95%CI = 1.42-7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC = 0.03, OR = 1.7, IC95% = 1.07-2.76, and a lack of protective alleles carrying aspartic acid⁷⁰, pC = 0.009, OR = 0.5, IC95% = 0.32-0.84.

Discussion: The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70-74.

Conclusion: Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives' risk of developing it.

Keywords: Autoimmune thyroid disease; Graves’ disease; HLA-DRB1; Hashimoto’s disease; Multiple autoimmunities; Rheumatoid arthritis; Shared epitope.