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T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs.

ABSTRACT: Antibodies in response to antigens are related to the immune repertoire of T- and B-cell receptors. However, some patients with chronic hepatitis B (CHB) have coexisting HBsAg and anti-HBsAg antibodies (anti-HBs) that cannot neutralize HBV. We attempted to investigate the repertoires that produce this response in CHB patients. The T-cell receptor β chain (TRB) and B-cell receptor (BCR) repertoires of peripheral blood genomic DNA were analyzed using MiXCR. T-cell receptor (TCR) cluster analysis was carried out by clusTCR, and motifs prediction was selected by Multiple Em for Motif Elicitation (MEME). A total of 76 subjects were enrolled, including 26 HBsAg and anti-HBs coexisting patients with CHB (DP group), 25 anti-HBs single-positive healthy people (SP group), and 25 CHB patients (CHB group). The clone length of BCR in 39, 90 was significantly different among these groups (p = 0.005, 0.036). The motif "CASSLG" in the DP group was significantly higher than SP and CHB groups and may relate to coexistence, and the motif "GAGPLT" was only shown in the SP group and may relate to anti-HB expression. These provide important insights into vaccine development and CHB treatment.

SUBMITTER: Zhan Q

PROVIDER: S-EPMC9318409 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. METHODS:During 2014-2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. RESULTS:(1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. CONCLUSIONS:HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

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T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs.

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