# Impact of the Human Leukocyte Antigen Complex on Idiopathic Pulmonary Fibrosis Development and Progression in the Sardinian Population

## TL;DR

This study investigates how specific HLA genes influence the progression of idiopathic pulmonary fibrosis in the Sardinian population, finding certain alleles linked to slower disease progression and better survival.

## Contribution

The study identifies specific HLA alleles and haplotypes associated with slower progression of IPF in a genetically distinct population, offering potential biomarkers for personalized therapies.

## Key findings

- HLA-DRB1*04:05 allele is associated with slower IPF progression and improved survival.
- An extended haplotype (HLA-A*30:02, B*18:01, C*05:01, DQA1*05:01, DQB1*02:01, DRB1*03:01) correlates with better pulmonary function and slower disease progression.
- Findings are independent of confounding factors and highlight the role of HLA in IPF outcomes.

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by the disruption of the alveolar and interstitial architecture due to extracellular matrix deposition. Emerging evidence suggests that genetic susceptibility plays a crucial role in IPF development. This study explores the role of human leukocyte antigen (HLA) alleles and haplotypes in IPF susceptibility and progression within the genetically distinct Sardinian population. Genotypic data were analyzed for associations with disease onset and progression, focusing on allele and haplotype frequencies in patients exhibiting slow (S) or rapid (R) progression. While no significant differences in HLA allele frequencies were observed between IPF patients and controls, the HLA-DRB1*04:05 allele and the extended haplotype (HLA-A*30:02, B*18:01, C*05:01, DQA1*05:01, DQB1*02:01, DRB1*03:01) were associated with a slower disease progression and improved survival (log-rank = 0.032 and 0.01, respectively). At 36 months, carriers of these variants demonstrated significantly better pulmonary function, measured with single-breath carbon monoxide diffusing capacity (DLCO%p) (p = 0.005 and 0.02, respectively). Multivariate analysis confirmed these findings as being independent of confounding factors. These results highlight the impact of HLA alleles and haplotypes on IPF outcomes and underscore the potential of the Sardinian genetic landscape to illuminate immunological mechanisms, paving the way for predictive biomarkers and personalized therapies.