PMID- 32366487 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1399-3003 (Electronic) IS - 0903-1936 (Print) IS - 0903-1936 (Linking) VI - 56 IP - 2 DP - 2020 Aug TI - A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis. LID - 10.1183/13993003.01380-2019 [doi] LID - 1901380 AB - BACKGROUND: Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies. METHODS: 170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20. RESULTS: 60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs(+)), and 110 hypersensitivity pneumonitis patients did not (HPAbs(-)). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs(+) group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83-237.1; p=1.65x10(-4) after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37-155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05-33.05; p=0.043). CONCLUSIONS: A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype. CI - Copyright (c)ERS 2020. FAU - Buendia-Roldan, Ivette AU - Buendia-Roldan I AD - Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Santiago-Ruiz, Luis AU - Santiago-Ruiz L AD - Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Perez-Rubio, Gloria AU - Perez-Rubio G AD - HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Mejia, Mayra AU - Mejia M AD - Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Rojas-Serrano, Jorge AU - Rojas-Serrano J AD - Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Ambrocio-Ortiz, Enrique AU - Ambrocio-Ortiz E AD - HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Benitez-Valdez, Geovanni AU - Benitez-Valdez G AD - Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. FAU - Selman, Moises AU - Selman M AUID- ORCID: 0000-0002-1022-4783 AD - Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico. AD - Joint lead authors. FAU - Falfan-Valencia, Ramces AU - Falfan-Valencia R AUID- ORCID: 0000-0001-6877-8124 AD - HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico rfalfanv@iner.gob.mx. AD - Joint lead authors. LA - eng PT - Journal Article DEP - 20200813 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 RN - 0 (Antibodies, Antinuclear) RN - 0 (Autoantibodies) RN - 0 (HLA-DQ beta-Chains) RN - 0 (HLA-DRB1 Chains) SB - IM MH - Alleles MH - *Alveolitis, Extrinsic Allergic/genetics MH - Antibodies, Antinuclear MH - Autoantibodies MH - *Autoimmune Diseases MH - Genetic Predisposition to Disease MH - HLA-DQ beta-Chains/genetics MH - HLA-DRB1 Chains/genetics MH - Haplotypes MH - Humans MH - *Sjogren's Syndrome PMC - PMC7424117 COIS- Conflict of interest: I. Buendia-Roldan has nothing to disclose. Conflict of interest: L. Santiago-Ruiz has nothing to disclose. Conflict of interest: G. Perez-Rubio has nothing to disclose. Conflict of interest: M. Mejia has nothing to disclose. Conflict of interest: J. Rojas-Serrano has nothing to disclose. Conflict of interest: E. Ambrocio-Ortiz has nothing to disclose. Conflict of interest: G. Benitez-Valdez has nothing to disclose. Conflict of interest: M. Selman has nothing to disclose. Conflict of interest: R. Falfan-Valencia has nothing to disclose. EDAT- 2020/05/06 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/08/13 CRDT- 2020/05/06 06:00 PHST- 2019/07/12 00:00 [received] PHST- 2020/04/13 00:00 [accepted] PHST- 2020/05/06 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/05/06 06:00 [entrez] PHST- 2020/08/13 00:00 [pmc-release] AID - 13993003.01380-2019 [pii] AID - ERJ-01380-2019 [pii] AID - 10.1183/13993003.01380-2019 [doi] PST - epublish SO - Eur Respir J. 2020 Aug 13;56(2):1901380. doi: 10.1183/13993003.01380-2019. Print 2020 Aug.