Polymorphisms within the and Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the and loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the genotype had a significantly increased risk of developing IA ( = 0.00022). We also found that carriers of the allele showed decreased serum levels of TNFSF14 protein ( = 0.0027), and that their macrophages had a decreased fungicidal activity ( = 0.048). In addition, we observed that each copy of the allele increased the risk of IA by 60% ( = 0.0017), whereas each copy of the allele was estimated to decrease the risk of developing the disease ( = 0.0029). Mechanistically, we found that carriers of the risk allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood ( = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin ( = 0.00097). Finally, we also found that carriers of the protective allele had decreased numbers of CD27-IgM-IgD- B cells ( = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells ( = 0.00018 and 0.00023). Altogether, these results suggest a role of the genes in determining IA risk.

PMID: 33374839