No abstract

Highlights d high SARS-CoV-2 IgG but overall reduced T cell immunity in active COVID-19 patients d PD-1, Tim-3, and active caspases in T cells result in impaired T cell function d stable SARS-CoV-2 T cell repertoire yet declining humoral responses during recovery d potentially protective role of pre-existing anti-huCoV CD4 + and CD8 + T cell immunity

Background: It has been reported that both sublingual (SLIT) and subcutaneous (SCIT) allergen-specific immunotherapy have clinical efficacy, yet there are rather few comparative placebo studies of children. We aimed to investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT versus a placebo in rhinitis and asthma in children. Methods: The outcomes of this 1-year, randomized, placebo-controlled, double-blind, double-dummy study were symptom and medication scores, visual analog scores (VAS), titrated skin prick tests, nasal and bronchial allergen provocation doses, serum house dust mite-specific immunglobulin E (HDM-sIgE), sIgG4, IL-10 and IFN-γ levels. Results: Clinical and laboratory parameters were evaluated in 30 patients. SCIT significantly diminished symptom and medication scores for rhinitis and asthma (p = 0.03 and p = 0.05 for rhinitis; p = 0.01 and p = 0.05 for asthma) and VAS. SLIT also reduced VAS, symptoms associated with rhinitis and asthma as well as medication usage for rhinitis, but this reduction was not significant when compared with the placebo. Skin reactivitiy to HDM and HDM-sIgE levels was reduced significantly in both immunotherapy groups. Serum IL-10 levels and nasal provocative doses increased significantly with both SCIT and SLIT. Nasal eosinophil increments after nasal challenge decreased with two treatment modes, but bronchial provocative doses and sputum eosinophil increments after bronchial challenge were reduced only with SCIT. In both treatment arms, there was no change in IFN-γ levels. Serum sIgG4 levels increased significantly only in the SCIT group. Conclusion: Based on the limited number of patients at the end of the 1-year immunotherapy, the clinical efficacy of SCIT on rhinitis and asthma symptoms was more evident when compared with the placebo.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

The family of IL-10-related cytokines includes several human members, , and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival and expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA + T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles.

Background-The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE and diminished inflammatory responses. It exists as autosomal dominant (AD) and recessive (AR) forms that manifest common and distinguishing clinical features. A majority of those with AD-HIES suffers from heterozygous mutations in Signal Transducer and Activator of Transcription 3 (STAT3) and impaired Th17 differentiation.

The prevalence of bronchiectasis (BR) has decreased significantly in industrialized countries, but is still commonplace in developing countries. We evaluated the causes and clinical features of BR in 23 children (13 boys (57%) and 10 girls (43%), with a mean age of 8.45 +/- 4.02 years). Infection was the major cause of BR in our region. In 8 patients, BR developed after tuberculosis or pneumonia, was associated with immune deficiency syndromes in 4 children, and with asthma in 4. Cystic fibrosis was diagnosed in 4 cases and ciliary dyskinesia in 3. In 10 patients, only one lobe was involved. Bronchiectatic lesions were most commonly found in the left lower lobe and were observed in 7 patients. Multilobar involvement was found in 13 patients. The initial treatment was primarily medical, but in 2 patients whose medical therapy failed, pulmonary resection was carried out. Three patients died from severe pulmonary infection and respiratory failure.

Altered Bone Morphogenetic Protein (BMP) signaling leads to multiple developmental defects, including brachydactyly and deafness. Here we identify chondroitin synthase 1 (CHSY1) as a potential mediator of BMP effects. We show that loss of human CHSY1 function causes autosomal-recessive Temtamy preaxial brachydactyly syndrome (TPBS), mainly characterized by limb malformations, short stature, and hearing loss. After mapping the TPBS locus to chromosome 15q26-qterm, we identified causative mutations in five consanguineous TPBS families. In zebrafish, antisense-mediated chsy1 knockdown causes defects in multiple developmental processes, some of which are likely to also be causative in the etiology of TPBS. In the inner ears of zebrafish larvae, chsy1 is expressed similarly to the BMP inhibitor dan and in a complementary fashion to bmp2b. Furthermore, unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation, indicating that Bmp signaling affects inner-ear development by repressing chsy1. In addition, we obtained strikingly similar zebrafish phenotypes after chsy1 overexpression, which might explain why, in humans, brachydactyly can be caused by mutations leading either to loss or to gain of BMP signaling.