A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis

Abstract

Background Hypersensitivity pneumonitis (HP) is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with HP 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 HP is unknown. We evaluated the association between HLA class II alleles and HP patients with and without autoantibodies. Methods One hundred seventy HP 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, ANCA, and anti-DNA. HLA typing was performed by PCR-SSP in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSSv20. Results Sixty HP patients showed sera autoantibodies (HPAbs+), and 110 HP 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=1.65E-04 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). Also, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with HP (adjusted OR=5.9, 95%IC 1.05–33.05; p=0.043). Conclusions A subset of HP patients presents circulating autoantibodies and higher mortality, that are associated with some alleles of 8.1 ancestral haplotype.