The prognosis and immune repertoire characteristics of HBsAg and anti-HBs double positivity chronic hepatitis B patients

Abstract

Abstract Background: Coexistence of HBsAg and anti-HBs has been observed in some chronic hepatitis B patients, but the clinical outcomes and comprehensive characterization of immune microenvironmental changes for this specific population remain inconclusive. Methods: A retrospective analysis of 305 patients in Foshan City, Guangdong Province, China, was conducted to investigate the prognosis. Molecular immunology changes of HBsAg and anti-HBs dual-positive chronic HBV patients (DP) and recovery patients (RP) were detected using TCR and BCR immune repertoire sequencing technology. Results: Our findings revealed that 22.30% of the dual-positive patients in Foshan district, Guangdong province, were diagnosed with severe liver disease. Furthermore, immune repertoire sequencing demonstrated significant skewing in the diversities of TRB and BCR in the DP group compared to the RP group. V(D)J combinations, such as IGHV1-18/IGHD3-22/IGHJ5, IGHV1-8/IGHD6-13/IGHJ3, and IGHV1-8/IGHD6-19/IGHJ3, along with TRBV12-3/TRBD1/TRBJ1-5 and TRBV11-2/TRBD2/TRBJ2-1, emerged as potential biomarkers for diagnosing the DP group. Additionally, distinct amino acid motifs in the TCR CDR3 of DP and HC groups, compared to the RP group, were identified. Notably, motifs "xxxYDSSGYx" and "AREx" in the BCR were selectively prevalent in the DP group, suggesting their potential to specifically identify the DP group from the RP group. Conclusions:These findings provide evidence for the poor clinical prognosis of dual-positive chronic HBV patients, offer new insights for the study of immune microenvironmental changes and pathogenesis, and may contribute to the development of potential diagnostic biomarkers and therapeutic targets for the DP group.