Association of HLA-Ib (HLA-G, HLA-E and HLA-F) with spontaneous HBV clearance.

Abstract

Background: The natural history of HBV infection is highly heterogeneous. Failure to clear the virus during the acute phase of infection allows for viral persistence and progression to chronicity. Investigating the immune mechanisms involved in this process is crucial for effectively managing infection outcome. HLA-Ib molecules (HLA-G, HLA-E and HLA-F) play a critical role in regulating the immune response.

Objectives: primary objective: we investigate the potential impact of functional polymorphisms in HLA-F*01:03 (rs1736924), HLA-E*01:01/01:03 (rs1264457), and two selected HLA-G polymorphisms in Exon 2 (+292 A > T (rs41551813) and +372 G > A (rs1130355)) on HBV infection outcome. Secondary objective: we evaluate the expression of soluble HLA-E in our cohort.

Methods: We evaluated these polymorphisms in a cohort of 200 patients with chronic HBV infection and 100 individuals who spontaneously resolved the infection, using SSP-PCR and Sanger sequencing. Additionally, we measured soluble HLA-E (sHLA-E) levels using ELISA.

Results: Our results showed a significant association of HLA-G (rs41551813) and HLA-E (rs1264457) polymorphisms with HBV infection outcome, where carriers of the A allele in both HLA-G (rs41551813) and HLA-E (rs1264457) had a significantly higher likelihood of spontaneous HBV clearance (all p < 0.01). Furthermore, we demonstrate that elevated sHLA-E expression favours HBV persistence. Additionally, our findings has revealed that the HLA-G + 292 A > T polymorphism (rs41551813) is associated with regulation of sHLA-G expression. Haplotype analysis further identified the 'TAAA' haplotype as linked to spontaneous HBV clearance.

Conclusion: this study demonstrates, for the first time, the critical role of HLA-Ib on HBV infection outcome, providing insights for potential therapeutic interventions.