Role of HLA-G in Sardinian Idiopatic Pulmonary Fibrosis patients.

<bold>Background and Aims:</bold> Idiopathic pulmonary fibrosis (IPF) is a rare disease of unknown origin that results in fibrosis that worsens over time with varying rates of progression. Both rare and common genetic factors, including those within the Human leukocyte antigens (HLA) genes, are known to influence susceptibility to the disease. However, the role non-classical HLA genes have not been fully elucidated. In this study, we explored the impact of HLA-G alleles and 3'UTR haplotypes, as well as plasma soluble HLA-G (sHLA-G), on disease progression in Sardinian IPF patients. The genetic isolation and homogeneity of this population offer an exceptional research setting for a rare disease. <bold>Methods:</bold> We compared a cohort of 180 healthy individuals and 106 Sardinian IPF patients, categorized based on disease severity, from stable (SP) to rapid disease progression (RP). Analysis of HLA-G alleles and 3'UTR haplotypes was conducted for both patients and controls. Additionally, plasma sHLA-G levels were measured. <bold>Results:</bold> Our findings revealed an overlap of the HLA-G allele frequency between patients and controls. Interesting, the HLA-G 01:01:01:08 allele was significantly more frequent in group SP compared to group RP [23/84 (27.38%) vs. 14/128 (10.77%), respectively; OR = 3.124 (95% CI 1.501 – 6.503); p = 0.003]. <bold>Conclusion:</bold> Our study suggests that the genetic variability of HLA-G may influence disease progression. In particular, the presence of HLA-G 01:01:01:08 allele is associated to slower evolution of the disease. Further investigations are necessary to elucidate the complex mechanisms underlying the role of HLA-G in IPF pathogenesis and progression.