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.
Among hypersensitivity pneumonitis (HP) patients have been identified who develop autoantibodies with and without clinical manifestations of autoimmune disease. Genetic factors involved in this process and the effect of these autoantibodies on the clinical phenotype are unknown. Matrix metalloproteinases (MMPs) have an important role in architecture and pulmonary remodeling. The aim of our study was to identify polymorphisms in the MMP1, MMP2, MMP9 and MMP12 genes associated with susceptibility to HP with the presence of autoantibodies (HPAbs+). Using the dominant model of genetic association, comparisons were made between three groups. For rs7125062 in MMP1 (CC vs. CT+TT), we found an association when comparing groups of patients with healthy controls: HPAbs+ vs. HC (p < 0.001, OR = 10.62, CI 95% = 4.34–25.96); HP vs. HC (p < 0.001, OR = 7.85, 95% CI 95% = 4.54–13.57). This rs11646643 in MMP2 shows a difference in the HPAbs+ group by the dominant genetic model GG vs. GA+AA, (p = 0.001, OR = 8.11, CI 95% = 1.83–35.84). In the linear regression analysis, rs11646643 was associated with a difference in basal forced vital capacity (FVC)/12 months (p = 0.013, β = 0.228, 95% CI95% = 1.97–16.72). We identified single-nucleotide polymorphisms (SNPs) associated with the risk of developing HP, and with the evolution towards the phenotype with the presence of autoantibodies. Also, to the decrease in plasma MMP-2 levels.
Objective. To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. Materials and methods. We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. Results. The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/μL (IQR, 0.050–0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Conclusion. Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.
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