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Identification of HLA-DRB1 association to adalimumab immunogenicity

Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associat...

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Autores principales: Liu, Mohan, Degner, Jacob, Davis, Justin Wade, Idler, Kenneth B., Nader, Ahmed, Mostafa, Nael M., Waring, Jeffrey F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882140/
https://www.ncbi.nlm.nih.gov/pubmed/29614084
http://dx.doi.org/10.1371/journal.pone.0195325
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author Liu, Mohan
Degner, Jacob
Davis, Justin Wade
Idler, Kenneth B.
Nader, Ahmed
Mostafa, Nael M.
Waring, Jeffrey F.
author_facet Liu, Mohan
Degner, Jacob
Davis, Justin Wade
Idler, Kenneth B.
Nader, Ahmed
Mostafa, Nael M.
Waring, Jeffrey F.
author_sort Liu, Mohan
collection PubMed
description Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associated with autoantibody formation against interferons and other TNF inhibitors, but not adalimumab. We analyzed samples from 634 subjects with either rheumatoid arthritis (RA) or hidradenitis suppurativa (HS): 37 subjects (17 RA and 20 HS) developed AAA (AAA+) during adalimumab treatment and 597 subjects (348 RA, 249 HS) did not develop AAA (AAA-) during the clinical trials. Using next-generation sequencing-based HLA typing, we identified three protective HLA alleles (HLA-DQB1*05, HLA-DRB1*01,and HLA-DRB1*07) that were less prevalent in AAA+ than AAA–subjects (ORs: 0.4, 0.25 and 0.28, respectively; and P values: 0.012, 0.012 and 0.018, respectively) and two risk HLA alleles (HLA-DRB1*03 and HLA-DRB1*011) that were more abundant in AAA+ than AAA–subjects (ORs: 2.52, and 2.64, respectively; and P values: 0.006 and 0.019). Similar to the finding of Billiet et al. who found that carriage of the HLA-DRB1*03 allele was more prevalent in those with anti-infliximab antibodies (OR = 3.6, p = 0.002, 95% CI: [1.5,8.6]).), we found HLA-DRB1*03 allele was also more prevalent in anti-adalimumab positive (OR = 2.52, p = 0.006, 95% CI: [1.37,4.63]). The results suggest that specific HLA alleles may play a key role in developing AAAs in RA and HS patients treated with adalimumab.
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spelling pubmed-58821402018-04-13 Identification of HLA-DRB1 association to adalimumab immunogenicity Liu, Mohan Degner, Jacob Davis, Justin Wade Idler, Kenneth B. Nader, Ahmed Mostafa, Nael M. Waring, Jeffrey F. PLoS One Research Article Anti-drug antibody formation occurs with most biological agents across disease states, but the mechanism by which they are formed is unknown. The formation of anti-drug antibodies to adalimumab (AAA) may decrease its therapeutic effects in some patients. HLA alleles have been reported to be associated with autoantibody formation against interferons and other TNF inhibitors, but not adalimumab. We analyzed samples from 634 subjects with either rheumatoid arthritis (RA) or hidradenitis suppurativa (HS): 37 subjects (17 RA and 20 HS) developed AAA (AAA+) during adalimumab treatment and 597 subjects (348 RA, 249 HS) did not develop AAA (AAA-) during the clinical trials. Using next-generation sequencing-based HLA typing, we identified three protective HLA alleles (HLA-DQB1*05, HLA-DRB1*01,and HLA-DRB1*07) that were less prevalent in AAA+ than AAA–subjects (ORs: 0.4, 0.25 and 0.28, respectively; and P values: 0.012, 0.012 and 0.018, respectively) and two risk HLA alleles (HLA-DRB1*03 and HLA-DRB1*011) that were more abundant in AAA+ than AAA–subjects (ORs: 2.52, and 2.64, respectively; and P values: 0.006 and 0.019). Similar to the finding of Billiet et al. who found that carriage of the HLA-DRB1*03 allele was more prevalent in those with anti-infliximab antibodies (OR = 3.6, p = 0.002, 95% CI: [1.5,8.6]).), we found HLA-DRB1*03 allele was also more prevalent in anti-adalimumab positive (OR = 2.52, p = 0.006, 95% CI: [1.37,4.63]). The results suggest that specific HLA alleles may play a key role in developing AAAs in RA and HS patients treated with adalimumab. Public Library of Science 2018-04-03 /pmc/articles/PMC5882140/ /pubmed/29614084 http://dx.doi.org/10.1371/journal.pone.0195325 Text en © 2018 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Liu, Mohan
Degner, Jacob
Davis, Justin Wade
Idler, Kenneth B.
Nader, Ahmed
Mostafa, Nael M.
Waring, Jeffrey F.
Identification of HLA-DRB1 association to adalimumab immunogenicity
title Identification of HLA-DRB1 association to adalimumab immunogenicity
title_full Identification of HLA-DRB1 association to adalimumab immunogenicity
title_fullStr Identification of HLA-DRB1 association to adalimumab immunogenicity
title_full_unstemmed Identification of HLA-DRB1 association to adalimumab immunogenicity
title_short Identification of HLA-DRB1 association to adalimumab immunogenicity
title_sort identification of hla-drb1 association to adalimumab immunogenicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882140/
https://www.ncbi.nlm.nih.gov/pubmed/29614084
http://dx.doi.org/10.1371/journal.pone.0195325
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