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

Abstract

BackgroundHypersensitivity 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.MethodsOne 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.ResultsSixty 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).ConclusionsA subset of HP patients presents circulating autoantibodies and higher mortality, that are associated with some alleles of 8.1 ancestral haplotype.

Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges

“…Several factors may hamper the resolution of the inflammation, including further exposure to the antigen, which occurs mainly when it has not been identified ( 20 ), cigarette smoking, a genetic predisposition that may enhance the development of autoantibodies ( 21 ), and other unknown factors.…”

“…Two recent studies have demonstrated that a subset of patients with HP presents circulating present autoantibodies, without features of autoimmune disease ( 21 , 60 ). In both studies, the presence of autoantibodies was an independent predictor of increased mortality.…”

Role of the Host Genetic Susceptibility to 2009 Pandemic Influenza A H1N1

“…Although it has been reported that some genes involved in inflammation are associated with respiratory diseases [ 87 , 88 , 89 , 90 , 91 , 92 ], investigations regarding genetic factors involved in the susceptibility and severity are scanty. Two primary examples in inflammatory response genes, where genetic variability is associated with an altered phenotype, are TNF-α and IL-1β; both are pleiotropic modulators critical in regulating inflammation.…”

SNP and Haplotype Interaction Models Reveal Association of Surfactant Protein Gene Polymorphisms With Hypersensitivity Pneumonitis of Mexican Population

“…Group 1 (Cases) was composed of 75 consecutive unrelated patients 18 years of age or older with a diagnosis of HP ( Table 1). HP was diagnosed as previously described using clinical characteristics, history of antecedent antigen exposure and specific antibodies against avian proteins, pulmonary function tests, high-resolution computed tomography, BAL findings (all 75 patients), and/or surgical biopsy when available (23 out of 75 patients) (1,36). Attending clinicians systematically recorded the relevant data in every patient before making the final diagnosis and was confirmed by a multidisciplinary team.…”