HLA profiles and susceptibility to Alveolar echinococcosis: evidence from a large cohort with population and household controls

Alveolar echinococcosis (AE) is an emerging and potentially fatal helminthic disease. Despite widespread environmental contamination with infective Echinococcus multilocularis (EM) eggs in endemic areas, human AE remains rare, suggesting an important role of host genetic susceptibility. In this case–control study, HLA variation was assessed by amplicon-based next-generation sequencing in 360 patients with AE and compared with (i) 1,440 population controls matched, where feasible, on age, sex, and place of residence, and (ii) 100 unrelated household controls to account for shared environmental exposure to EM. Analyses included age- and sex-adjusted Firth-penalized logistic regression, linkage disequilibrium (LD)-aware haplotype analyses, simulation-based maximum-score tests, and Benjamini–Hochberg false discovery rate correction. At two-field resolution, C*07:01 was associated with increased AE odds (OR 2.10; adjusted p = 0.006), whereas B*18:01 was associated with reduced odds (OR 0.49; adjusted p = 0.014). Haplotype analyses identified an extended LD-defined background involving A*29, C*16, or both, frequently combined with B*44, DRB1*07, or DQB1*02. A*29 carriage corresponded to the A01–A24 supertype category. A*29–DQB1*02 remained significant after within-model and study-wide correction (OR 3.92; adjusted p = 0.005 and 0.039, respectively), while C*16–B*44–DQB1*02 remained significant after within-model correction (OR 2.83; adjusted p = 0.041) but not after study-wide correction. Exploratory analyses of early-onset AE (≤35 years; n = 63) suggested associations with A*31:01 (OR 2.86) and DQB1*05:03 (OR 3.44), although neither remained significant after multiple-testing correction. These findings support a contribution of individual HLA alleles and extended haplotypic backgrounds to AE susceptibility within a multifactorial host–environment model.