SARS-CoV-2-Specific Adaptive Immunity in COVID-19 Survivors With Asthma.

Background: Asthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear. Methods: COVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects. Results: The strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002; and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003; and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485; all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up. Conclusion: The level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.

The prevalence of hereditary angioedema in a Chinese cohort with decreased complement 4 levels.

OBJECTIVE: Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant disorder. We aimed to investigate the prevalence of HAE in a Chinese population with a decreased Complement 4 (C4) level. METHODS: All the patients present in Tongji Hospital with C4 below lower normal range were included from January 2019 to June 2020. The individual data were extracted from the database and categorized by diagnosis. Patients suspected of HAE were further evaluated by C1 inhibitor level and function test to confirm the HAE diagnosis. RESULTS: A total of 8226 patients were enrolled in our study, among whom 18 had symptoms similar to HAE and received C1 inhibitor level and function tests. Two (1 male and 1 female) of the 18 patients were identified as HAE patients. This means the prevalence of HAE was 2.43/10 000 among the C4-decreased population and 10.1/10 000 in the C4-decreased population with etiology undetermined. The 2 HAE patients had experienced skin and oropharynx edema attack and received tracheotomy. The female patient had a family history. Laboratory tests showed significant decrease of C4 and C1 inhibitor levels in the 2 patients, both of whom were diagnosed as type 1 HAE. CONCLUSION: The prevalence of HAE is low in C4-decreased patients. In a large cohort, C4 level can serve as a practical indicator to screen the HAE patients, but further testing of C1 inhibitor activity and levels is needed to confirm the diagnosis of HAE.

IgE and IgG4 Repertoire in Asymptomatic HDM-Sensitized and HDM-Induced Allergic Rhinitis Patients.

INTRODUCTION: Asymptomatic sensitization is defined as the presence of positive skin prick test (SPT) and/or positive serum allergen-specific IgE in the absence of clinical allergic symptoms. Currently, there is no convincing explanation why some people with positive allergen tests do not show symptoms. We aimed to investigate the house dust mite (HDM)-specific IgE and IgG4 repertoire in asymptomatic HDM-sensitized subjects and HDM-induced allergic rhinitis (AR) patients. METHODS: A total of 48 subjects sensitized to HDM were included in this study: 27 had AR with/without asthma (symptomatic group), and 21 had no allergic symptoms (asymptomatic group). Six healthy individuals served as control group. Peripheral blood samples were collected for serum IgE and IgG4 assay and basophil activation tests (BATs). IgE and IgG4 assay included antibodies to Dermatophagoides (Der) p1, 2, 7, 10, 21, 23, and Der f1, 2. RESULTS: AR patients had a larger wheal diameter of SPT (7.0 vs. 3.0 mm, p < 0.0001) and a higher specific IgE to Der p (15.50 vs. 0.70 KU/L, p < 0.0001) than asymptomatic subjects. They also showed more frequent sensitization to Der p1 and Der p2 (both p < 0.05). However, the total IgE and specific IgG4 did not differ significantly between the 2 groups. The basophil activation response after being stimulated with HDM was observed to be higher in AR patients (all p < 0.05). CONCLUSIONS: There are differences in SPT, serum-specific IgE to Der p, component allergen Der p1 and Der p2 level and BAT between AR patients and asymptomatic subjects sensitized to HDM. IgG4 alone cannot differentiate asymptomatic individuals from AR patients.

Specific IgE and IgG4 Profiles of House Dust Mite Components in Allergen-Specific Immunotherapy.

Background: Allergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited. Objective: We sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses. Methods: Sixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components (Derp 1, Derf 1, Derp 2, Derf 2, Derp 7, Derp 10, Derp 21 and Derp 23) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly. Results: In the AIT group, sIgG4 to the HDM components of Derp 1, Derf 1, Derp 2 and Derf 2, Derp 21 significantly increased at Month 18 compared to the baseline (36.2 UA/mL vs 158.8 UA/mL, 46.4 UA/mL vs 94.6 UA/mL, 80.5 UA/mL vs 152.3 UA/mL, 78.3 UA/mL vs 205.1 UA/mL, 42.3 UA/mL vs 59.3 UA/mL, all p<0.05), sIgE to HDM components didn't see differences at baseline and at Month 18 (all p>0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both p<0.05). However, the changes of sIgE, sIgG4, sIgE/sIgG4 ratio and the numbers of positive HDM components had no correlations with the improvement of CSMS after AIT (all ρ<0.3). For the control group, the sIgE and sIgG4 did not change significantly during the observational period (all p>0.05). Conclusion: AIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.

Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway.

BACKGROUND: Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect. METHODS: Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3ß, p-GSK-3ß by Western bolting and mPTP opening. RESULTS: Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3ß. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it. CONCLUSIONS: Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3ß pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury.