Immunoglobulin repertoire restriction characterizes the serological responses of patients with predominantly antibody deficiency.

BACKGROUND: Predominantly antibody deficiency (PAD) is the most common category of inborn errors of immunity and is underpinned by impaired generation of appropriate antibody diversity and quantity. In the clinic, responses are interrogated by assessment of vaccination responses, which is central to many PAD diagnoses. However, the composition of the generated antibody repertoire is concealed from traditional quantitative measures of serological responses. Leveraging modern mass spectrometry-based proteomics (MS-proteomics), it is possible to elaborate the molecular features of specific antibody repertoires, which may address current limitations of diagnostic vaccinology. OBJECTIVES: We sought to evaluate serum antibody responses in patients with PAD following vaccination with a neo-antigen (severe acute respiratory syndrome coronavirus-2 vaccination) using MS-proteomics. METHODS: Following severe acute respiratory syndrome coronavirus-2 vaccination, serological responses in individuals with PAD and healthy controls (HCs) were assessed by anti-S1 subunit ELISA and neutralization assays. Purified anti-S1 subunit IgG and IgM was profiled by MS-proteomics for IGHV subfamily usage and somatic hypermutation analysis. RESULTS: Twelve patients with PAD who were vaccine-responsive were recruited with 11 matched vaccinated HCs. Neutralization and end point anti-S1 titers were lower in PAD. All subjects with PAD demonstrated restricted anti-S1 IgG antibody repertoires, with usage of <5 IGHV subfamilies (median: 3; range 2-4), compared to ≥5 for the 11 HC subjects (P < .001). IGHV3-7 utilization was far less common in patients with PAD than in HCs (2 of 12 vs 10 of 11; P = .001). Amino acid substitutions due to somatic hypermutation per subfamily did not differ between groups. Anti-S1 IgM was present in 64% and 50% of HC and PAD cohorts, respectively, and did not differ significantly between HCs and patients with PAD. CONCLUSIONS: This study demonstrates the breadth of anti-S1 antibodies elicited by vaccination at the proteome level and identifies stereotypical restriction of IGHV utilization in the IgG repertoire in patients with PAD compared with HC subjects. Despite uniformly pauci-clonal antibody repertoires some patients with PAD generated potent serological responses, highlighting a possible limitation of traditional serological techniques. These findings suggest that IgG repertoire restriction is a key feature of antibody repertoires in PAD.

Sex differences in clinical characteristics and risk factors for disease severity of hospitalized patients with COVID-19.

Recent studies reported sex differences in patients with coronavirus disease-2019 (COVID-19). We aim to analyze sex differences in clinical characteristics and risk factors for disease severity of hospitalized patients with COVID-19 in Beijing. All adults (185 cases) diagnosed with COVID-19 and admitted to Beijing Ditan Hospital, Capital Medical University were included in samples. The median age of all patients was 41 years. The mean body mass index (BMI) of males was relatively higher compared to females (p < 0.001). The proportion of male patients with coronary heart disease (CHD), nonalcoholic fatty liver disease (NAFLD), history of smoking and drinking was higher than females. Male patients developed more clinical symptoms, obtained more abnormal laboratory test results, while they were less aware of care-seeking than female patients. There were no significant differences in clinical complications and outcomes between two groups. Age (odds ratio [OR]: 1.082; 95% confidence interval [CI]: 1.034-1.132; p = 0.001) and BMI (OR: 1.237; 95% CI: 1.041-1.47; p = 0.016) were considered risk factors for refractory pneumonia in multivariate regression analysis. The findings of the current study showed that SARS-CoV-2 was more likely to affect older males with comorbidities. Further researches into factors underlying obesity and disease severity may provide mechanistic insight into COVID-19 development.

Pattern of liver injury in adult patients with COVID-19: a retrospective analysis of 105 patients.

BACKGROUND: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown. METHODS: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined. RESULTS: 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P <  0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge. CONCLUSIONS: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.