The repertoire of IgG antibody responses to infection and vaccination varies depending on the characteristics of the immunogen and the ability of the host to mount a protective immune response. Chronic hepatitis B virus (HBV) infections are marked by persistent infection and immune tolerance to vaccination. This disease offers a unique opportunity to discover key repertoire signatures during infection and in response to vaccination. Complementarity determining region 3 of an antibody heavy chain (CDR-H3) has a major impact on the antigenic specificity of an antibody. We used next-generation sequencing to characterize the CDR-H3 sequences in paired siblings of 4 families in which only one member of each pair had chronic HBV infection. Blood samples were obtained before and 2 weeks after HBV vaccination. The analysis revealed a huge network of sequence-related CDR-H3 clones found almost exclusively among carriers. In contrast, vaccination induced significant increases of CDR-H3 cluster diversities among siblings without hepatitis B. Several vaccination-associated clone clusters were identified. Similar findings of vaccination-associated clone networks were observed in healthy adults receiving HBV boosters. These strategies can be used to identify signatures of other infectious diseases and accelerate discoveries of antibody sequences with important biomedical implications.

HLA-A*0207 is the most common HLA-A2 subtype among Chinese. The high frequency of the HLA-A*0207 allele in this population offers a unique opportunity to study the ways in which different HLA-A2 subtypes may influence the clinical outcome of allograft transplantation and the disease susceptibility of recipients.

Phenotypic manifestations of infectious diseases are closely related to individual immune responses. Methods to extract information from patients’ own immune reactions would be of great use for both diagnosis and treatment. Dengue fever is one of the diseases that clinical aggravations could occur paradoxically after humoral immunity appears. This property makes dengue fever an excellent disease model to explore. A principal component analyses (PCAs)-based framework derived from a prior vaccination study was developed. The framework was verified by successful demonstrations of known IgG signatures from a Mexico Dengue data set. Afterward the pipeline was tested upon de novo IgG and IgA libraries of Dengue patients from southern Taiwan. We discovered four infection signatures within IgG repertoires, two of which were identical to previous reports. However, it was IgA but not IgG that could differentiate hemorrhagic from non-hemorrhagic patients. IgA repertoires were found more diversified among bleeders, from whom seven signature clusters were characterized. The expressions of transforming growth factor beta 1 ( TGFβ1 ) and accordingly mediated class-switch activity of IgA were distinct only among the PCA-segregated bleeding group. In sum, intercontinental sharing of IgG signatures in dengue fever was demonstrated via a unified working flow. Differential regulation of IgA class-switch with associated diversity expansion plus existences of hemorrhage-restricted clusters were shown. The ability of the framework to find common IgG signatures would implicate applications to infections even from unknown pathogens. The clusters within IgA repertoires could offer perspectives to other IgA-related bleeding disorders such as Henoch-Schönlein purpura or IgA nephropathy. Substantiated grounds for IgA-specific effector function via TGFβ1 -mediated class-switch would be a new factor to consider for infectious diseases.

BACKGROUND: The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remains unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolization, radiofrequency ablation. METHODS: Relevant randomized controlled trials (RCTs) were obtained from PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival, hospital stay, nutrition status, and biochemistry profile. The secondary outcomes were the complication rate of liver treatment and adverse effect of BCAA supplementation. RESULTS: In total, 11 RCTs involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumorrecurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference [MD]: 0.11 g/dL, 95% confidence interval [CI]: 0.02–0.20) at 6 months and cholinesterase level (MD: 50.00 U/L, 95% CI: 21.08–78.92) at 12 months, increased body weight (MD: 3.29 kg, 95% CI: 1.07–5.50) at 12 months, and reduced ascites incidence (risk ratio: 0.39, 95% CI: 0.21–0.71) compared with the control group. Additionally, BCAA administration shortened the hospital stay length (MD: −2.36 days, 95% CI: −4.78 to 0.07) compared with the control group. CONCLUSION: BCAA supplementation significantly reduced postintervention complication and hospitalization duration and increased body weight. Thus, BCAA supplementation may benefit patients undergoing liver intervention.