Coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) has been observed in some chronic hepatitis B (CHB) patients (DP patients), but the clinical outcomes and comprehensive characterization of immune micro-environmental changes for this specific population remain inconclusive. In this study, we retrospectively analyze the prognosis of 305 patients in Foshan City, Guangdong Province, China, and also investigated the molecular immunology changes in HBsAg and anti-HBs double positive CHB patients (DP group), CHB patients who had recovered from IFN-ɑ treatment (RP group), and healthy controls (HC group) using T cell receptor (TCR) and B cell receptor (BCR) immune repertoire sequencing. Our findings revealed that 22.30% of DP patients were diagnosed with severe liver disease. Immune repertoire sequencing revealed significant skewing in the diversities of T cell receptor β-chain (TRB) and immunoglobulin heavy chain (IGH) in the DP group compared to the RP group. Unique V(D)J gene combinations, such as IGHV1-18/IGHD3-22/IGHJ5, IGHV1-8/IGHD6-13/IGHJ3, and IGHV1-8/IGHD6-19/IGHJ3, as well as TRBV12-3/TRBD1/TRBJ1-5 and TRBV11-2/TRBD2/TRBJ2-1, exhibited distinct utilization patterns in the DP group. Moreover, the top ten most utilized amino acid motifs in the complementarity determining region 3 (CDR3) of TRB in the DP group showed significant differences from those in the RP group. Notably, motifs such as "xxxYDSSGYx" and "AREx" in the IGH CDR3s were selectively prevalent in the DP group. These findings are expected to provide evidence supporting the poor clinical prognosis of DP patients and offer new insights into the distinct immune micro-environmental changes of this group.
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