No abstract

IL-4, primarily produced by T cells, mast cells, and basophiles, is a cytokine which has pleiotropic effects on the immune system. IL-4 induces T cells to differentiate to Th2 cells and activated B lymphocytes to proliferate and to synthesize IgE and IgG1. IL-4 is particularly important for the development and perpetuation of asthma and allergy. Stat6 is the protein activated by signal transduction through the IL-4R, and studies with knockout mice demonstrate that Stat6 is critical for a number of IL-4-mediated functions including Th2 development and production of IgE. In the present study, novel IL-4- and Stat6-regulated genes were discovered by using Stat6−/− mice and Affymetrix oligonucleotide arrays. Genes regulated by IL-4 were identified by comparing the gene expression profile of the wild-type T cells induced to polarize to the Th2 direction (CD3/CD28 activation + IL-4) to gene expression profile of the cells induced to proliferate (CD3/CD28 activation alone). Stat6-regulated genes were identified by comparing the cells isolated from the wild-type and Stat6−/− mice; in this experiment the cells were induced to differentiate to the Th2 direction (CD3/CD28 activation + IL-4). Our study demonstrates that a number a novel genes are regulated by IL-4 through Stat6-dependent and -independent pathways. Moreover, elucidation of kinetics of gene expression at early stages of cell differentiation reveals several genes regulated rapidly during the process, suggesting their importance for the differentiation process.

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) was firstly characterized in 2006 in China. The virus has caused great economic loss to the Chinese swine production during the past years. Herein, we experimentally infected SPF pigs using two strains of PRRSV with different pathogenicity and observed the lung pathological changes looking for new sights on the possible pathogenesis associated with the virulence of HP-PRRSV. The results indicated that the HP-PRRSV-infected pigs died and exhibited severe pathological changes of lungs featuring increased neutrophils, mast cells and mononuclear macrophages, compared with the pigs inoculated with low pathogenic (LP-) PRRSV. Furthermore, the pigs infected with HP-PRRSV showed the higher levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-8 and histamine, leukotriene B4 (LTB4), platelet activation factor (PAF) in sera than those inoculated with LP-PRRSV. Additionally, the fibrosis of lung was observed in the HP-PRRSV-infected pigs. At present, our findings suggest that the aberrant immune responses triggered by HP-PRRSV infection are closely related to acute lung injury (ALI), and especially the pathological changes in lung vascular system are of particular significance. These associated pathological changes of lung are in part responsible for the additional morbidity and mortality observed in HP-PRRSV infection.

A total of 25 Chinese patients aged 6 to 36 months hospitalised at Beijing Children’s Hospital due to melamine-induced kidney stones complicated by acute obstructive renal failure in 2008 were included in a study in order to diagnose and treat these special cases more effectively. Feeding history, clinical presentation, ultrasound findings, treatments and effects were summarised. Twelve to seventeen months follow-up was reported also. Ultrasound examination showed that calculi were located at the kidney and ureters. Stones were composed of both uric acid and melamine in a molar ratio of 1.2:1 to 2.1:1. Treatments providing liquid plus alkalisation of urine proved to be effective in helping the patients pass the stones. Surgical intervention was needed in severe cases. Renal function returned to normal in all 25 patients after various durations of therapy. Sixty-eight percent of the patients expelled all of the calculi within 3 months, 90% in 6 months and 95% in 9 months, without sequelae till now. Melamine-contaminated milk formula can cause kidney stones in infants, which should be diagnosed by feeding history, clinical symptoms and ultrasound examination. Composition of the stones was not only of melamine but also uric acid. Providing liquid orally or intravenously plus alkalisation of urine proved to promote the removal of the stones. Follow-up of 12 to 17 months after discharge showed no sequelae.

Objective Information regarding the association of immune‐related factors with pneumonia in children with coronavirus disease 2019 (COVID‐19) is scarce. This study aims to summarize the immune‐related factors and their association with pneumonia in children with COVID‐19. Methods Children with COVID‐19 at Wuhan Children's Hospital from 28 January to 12 March 2020 were enrolled. Pneumonia due to causes other than COVID‐19 were excluded. The clinical and laboratory information including routine blood tests, blood biochemistry, lymphocyte subsets, immunoglobulins, cytokines, and inflammatory factors were analyzed retrospectively in 127 patients. Normal ranges and mean values of laboratory markers were applied as parameters for logistic regression analyses of their association with pneumonia. Results In nonintensive care unit patients, 48.8% and 22.4% of patients had increased levels of procalcitonin and hypersensitive C‐reactive protein (hs‐CRP) respectively. A total 12.6% and 18.1% of patients had decreased levels of immunoglobulin A (IgA) and interleukin 10 (IL‐10), respectively. Approximately 65.8% of patients had pneumonia. These patients had decreased levels of globulin (odds ratio [OR], 3.13; 95% confidence interval [CI] 1.41‐6.93; P = .005), IgA (OR, 4.00; 95% CI, 1.13‐14.18; P = .032), and increased levels of hs‐CRP (OR, 3.14; 95% CI, 1.34‐7.36; P = .008), procalcitonin (OR, 3.83; 95% CI, 2.03‐7.24; P < .001), IL‐10 (OR, 7.0; 95% CI, 1.59‐30.80; P = .010), and CD4+ CD25+ T lymphocyte less than 5.0% (OR, 1.93; 95% CI, 1.04‐3.61; P = 0.038). Conclusion Decreased IgA and CD4+ CD25+ T lymphocyte percentage, and increased hs‐CRP, procalcitonin, and IL‐10 were associated with pneumonia, suggesting that the immune‐related factors may participate in the pathogenesis of pneumonia in children with COVID‐19.

Background: B-cell-deleted therapy has been successfully used for children with idiopathic nephrotic syndrome (INS), suggesting that B cells may be involved in the pathogenesis of INS. B cells are a heterogenous population comprised of subpopulations distinguished by their phenotypes. However, few studies have focused on the alteration of B-cell homeostasis in INS.Methods: We measured the levels of B-cell subsets in the blood of 87 INS children via flow cytometry, prior to treatment with steroids. INS patients were divided into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) groups based on their sensitivities to steroids after a one-month follow-up. Subsequently, we compared these INS patients with age- and sex-matched patients with relapse (n = 35) and remissions (n = 32), as well as healthy controls (n = 75).Results: We found that 65 SSNS patients exhibited an altered peripheral-blood B-cell-subset distribution, with increased levels of total, transitional, memory, IgM (immunoglobulin M) memory and switched-memory B cells compared to 22 SRNS patients. The proportion of total B cells was significantly higher in the SSNS group (22.1 ± 6.7% L, p < 0.001) than in the SRNS, remission, and control groups. In contrast, the levels of B-cell subsets in SRNS patients were generally the same as those in remission patients and healthy controls. Patients in relapse presented elevated memory B cells compared to those in other groups. The area under the ROC (receiver operating characteristic) curve of transition B cells at initial onset for the prediction of SSNS was 0.907 (95% confidence interval, 0.835–0.979). The analysis rendered an optimal cut-off value of 2.05 (% Lymphocyte) corresponding to 79.1% sensitivity and 90.9% specificity.Conclusions: We observed and verified that B-cell subsets are significantly altered in children with SSNS. We propose that elevated transitional B cells may be a promising marker for predicting successful immunosuppressive therapy during the initial onset of INS. Further research is needed to determine the function of memory B cells in INS.

Background: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. Methods: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model. The mRNA and protein levels of Interleukin (IL)-6 were detected by qPCR and ELISA respectively. The signaling pathway-related proteins were investigated by western blot and immunofluorescence assay. Results: HBcAg increased the expression and secretion of IL-6 through activating extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB). These activations can be blocked by specific inhibitors of the three pathways. Conclusions: HBcAg actives p38, ERK1/2 and NF-κB to enhance the production of IL-6 in hepatocytes. This provides a molecular mechanism to explain the association of cytoplasmic HBcAg with severe liver injury and inflammation.

CD40 ligand (CD40L) deficiency is a rare but life‐threatening primary immunodeficiency caused by mutations in the CD40L gene. Here, we investigated a cohort of 40 genetically diagnosed CD40L‐deficient patients from the Chinese mainland, analysed their clinical and genetic data, and examined CD40L expression, the proportion of T cell subsets, B cell subsets and T follicular helper (Tfh) cells. The aim was to provide a complete picture of CD40L deficiency. Initial presentations of the patient cohort mainly involved recurrent fever (47.5%) and sinopulmonary infection (42.5%). Life‐threatening infections (42.5%), caused by various pathogens, were the most serious threats faced by CD40L‐deficient patients, while neutropenia (57.5%) remained the most common complication. Opportunistic infections, including Pneumocystis carinii pneumonia and invasive fungal disease associated with Talaromyces marneffei, were also common in the cohort. In addition, seven patients (17.5%) suffered BCGitis/BCGosis, which is a major problem facing a planned immunization programme in China. It was intriguing that reduced IgM levels were observed in 12.5% of patients, while normal or elevated IgA levels were shown in 47.5% of patients. Thirty‐seven unique mutations were identified in 40 patients; of these, 10 were novel. Furthermore, we observed a lower percentage of NK cells, Tfh cells, and central memory CD4+ T cells, and an extremely small class‐switched memory B cell population, in CD40L‐deficient patients. Patients who underwent hematopoietic stem cell transplantation experienced better disease remission. Taken together, our data establish the largest database about CD40L deficiency in China and provide genetic, immunologic and clinical information about Chinese CD40L‐deficient patients.