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, includingHLA-DRB1andHLA-DQB1loci. 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 alleleHLA-DRB1*03:01was remarkably increased in the HPAbs⁺group (10.8%versus0.45%; OR 30.14, 95% CI 3.83–237.1; p=1.65×10^-4after Bonferroni's correction). Likewise, we found that the haplotypeDRB1*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, theHLA-DRB1*03:01allele 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.

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.

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.

Liver cancer is the fourth leading cause of cancer-related death worldwide. In Mexico, there is a high burden of liver cancer mortality in rural states, affecting both women and men equally. Thus, we aimed to describe the demographic and clinical characteristics of hepatocellular cancer (HCC) by sex in Mexico. Demographic and clinical information was extracted retrospectively from the medical records of patients with HCC initially treated (2015–2022) at institutions participating in a national survey across the country. The male-to-female ratio was calculated at the national and regional levels, and the results were stratified by sex. Among 697 HCC patients, the age at diagnosis was 65.4 ± 11.9 years and 20% were diagnosed at ≥75 years. The male-to-female ratio was 1.4:1, ranging from 1:1 in the northwestern and southwestern regions, to 2.1:1 in the western region. The proportion of cirrhosis was similar between the sexes; however, the etiology of cirrhosis differed: cryptogenic cirrhosis was higher in women and alcohol consumption was higher in men. Men had a higher proportion of advanced HCC, poor/undifferentiated tumors, and ≥4 nodules than women. HCC in the Mexican population affects both men and women at a 1.4:1 male-to-female ratio. This unique proportion by sex could be explained by the differences in the prevalence of risk factors across our heterogeneous country.

Background: Recently it has been identified a subgroup of patients with hypersensitivity pneumonitis (HP) that develop autoantibodies with/out clinical manifestations of autoimmune disease. Genetic factors involved in this process, and the effect of these autoantibodies on clinical course are largely unknown. Matrix metalloproteinase (MMP) have an important role in the architecture and pulmonary remodeling, they have been little studied in the different HP phenotypes. Aim: To identify MMP1, MMP2, MMP9, MMP12 gene polymorphisms associated with susceptibility to HP with (HPAb+) and without autoantibodies (HP). Methods: 34 HPAb+ and 104 HP patients were included. Autoimmune laboratory profile included ANA, RF, anti-SSA/Ro, anti-SSB/La, anti-Scl70 and anti-CCP. In addition, a group of 184 healthy subjects (HC). 12 SNP were genotyped in 4 genes: MMP1, MMP2, MMP9, MMP12 using allelic discrimination by qPCR. Results: Using the dominant model of genetic association, comparisons between the three groups were performed. For rs7125062 in MMP1 (CC versus CT+TT), an association was found when comparing groups of patients with healthy subjects: HPAb+ vs. HC (p=8.6E-09, OR=10.62, CI95%=4.34-25.96); HP vs. HC (p<0.001, OR=7.85, CI95%=4.54-13.57). rs11646643 in MMP2, shows a difference in the HPAb+ group by the dominant genetic model GG vs. GA+AA, (p=1.4E-03, OR=8.11, CI95%=1.83-35.84). In the linear regression analysis, rs11646643 (GA+AA) was associated to a difference in basal/12months FVC (p=0.013, b=0.228, ci95%=1.97-16.72). Conclusions: There are SNPs associated to risk increased of developing HP, and with the evolution towards to phenotype autoantibodies-positive.