# Chronic Pulmonary Aspergillosis: Genomic Variant Analysis and Protein Dysfunction Susceptibility in a Brazilian Cohort

## TL;DR

This study explores genetic variants in Brazilian patients with chronic pulmonary aspergillosis to understand their role in immune dysfunction and disease susceptibility.

## Contribution

The first use of a custom multigenic panel to investigate CPA susceptibility in a Brazilian cohort.

## Key findings

- SNVs in genes like CX3CR1, IL12B, and IL4R were identified as variants of uncertain significance.
- Protein–protein interaction analysis suggests these variants may contribute to immune evasion and dysfunction.
- The study highlights the potential for future functional and clinical research in fungal immunogenetics.

## Abstract

Background/Objectives: Chronic pulmonary aspergillosis (CPA) is a debilitating condition often affecting immunocompetent patients with underlying structural lung diseases, particularly pulmonary tuberculosis. This study investigates single nucleotide variants (SNVs) in immunogenetic-related genes among a Brazilian cohort with CPA. Methods: Twelve patients with confirmed CPA, based on ESCMID/ERS criteria, were sequenced using custom multigenic panel sequencing. Variants were annotated, classified using ACMG guidelines, and analyzed for potential impact on protein interactions and immune pathways. Results: A set of SNVs in CX3CR1, IL12B, IL4R, PTX3, CCR5, and IFNG genes were classified as variants of uncertain significance (VUS), but protein–protein interaction analysis suggests a potential role in immune evasion and dysfunction. Conclusions: This is the first study to apply a custom multigenic panel for CPA susceptibility in a Brazilian cohort, contributing to future functional and clinical studies in fungal immunogenetics.