Aspartic acid 70 in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans
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. I...
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Published in | Journal of translational autoimmunity (Online) Vol. 3; p. 100057 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
2020
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Abstract | 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.
High-resolution HLA class II typing was performed using a sequence-based method.
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 acid
, pC = 0.009, OR = 0.5, IC95% = 0.32-0.84.
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.
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. |
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AbstractList | 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.
High-resolution HLA class II typing was performed using a sequence-based method.
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 acid
, pC = 0.009, OR = 0.5, IC95% = 0.32-0.84.
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.
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. |
Author | Jakez, Juan Valdés-Corona, Luis Francisco García-Silva, Rafael Rodríguez-Reyna, Tatiana Sofia Lima, Guadalupe Yunis, Edmond Pineda, Carlos Llorente, Luis Hernández-Doño, Susana Granados, Julio Escamilla-Tilch, Monica |
Author_xml | – sequence: 1 givenname: Luis Francisco surname: Valdés-Corona fullname: Valdés-Corona, Luis Francisco organization: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 2 givenname: Susana surname: Hernández-Doño fullname: Hernández-Doño, Susana organization: Immunogenetics Division, Transplant Department. Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 3 givenname: Tatiana Sofia surname: Rodríguez-Reyna fullname: Rodríguez-Reyna, Tatiana Sofia organization: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 4 givenname: Rafael surname: García-Silva fullname: García-Silva, Rafael organization: Immunogenetics Division, Transplant Department. Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 5 givenname: Juan surname: Jakez fullname: Jakez, Juan organization: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 6 givenname: Monica surname: Escamilla-Tilch fullname: Escamilla-Tilch, Monica organization: Centro Medico 20 de Noviembre, ISSSTE, Mexico – sequence: 7 givenname: Guadalupe surname: Lima fullname: Lima, Guadalupe organization: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 8 givenname: Luis surname: Llorente fullname: Llorente, Luis organization: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico – sequence: 9 givenname: Carlos surname: Pineda fullname: Pineda, Carlos organization: Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico – sequence: 10 givenname: Edmond surname: Yunis fullname: Yunis, Edmond organization: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, USA – sequence: 11 givenname: Julio surname: Granados fullname: Granados, Julio organization: Immunogenetics Division, Transplant Department. Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, Mexico |
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Keywords | Hashimoto’s disease Shared epitope Graves’ disease Rheumatoid arthritis Multiple autoimmunities Autoimmune thyroid disease HLA-DRB1 |
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Title | Aspartic acid 70 in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans |
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