IMPORTANCE Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. OBJECTIVE To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat. INTERVENTIONS Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels. RESULTS After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, −13.7 to −4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, −38.6 to −4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = −0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study. CONCLUSIONS AND RELEVANCE Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01638234

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Asthma is one of the most common chronic airway inflammatory diseases. The induction of immunologic tolerance via mucosa has been used for treating allergic diseases. B cells, which comprise the major cell population in Peyer's patches, were shown to induce the development of regulatory T (Treg) cells. This study investigated the role of B cells in Peyer's patches regarding the induction of tolerance and Treg cell functions. An in vitro suppressive assay and ELISA were used to evaluate the function of T cells stimulated by Peyer-patch B cells (Treg-of-B cells). The therapeutic potential of Treg-of-B cells was then evaluated by an animal model of airway inflammation. Treg-of-B cells were found to exert a suppressive function on T-cell proliferation. Antigen-loaded B cells isolated from Peyer's patches were more tolerogenic, and had the potential to generate more suppressive Treg-of-B cells via the production of IL-10 and cell-cell contacts. Treg-of-B cells expressed cytotoxic T lymphocyte antigen 4, inducible costimulator, OX40 (CD134), programmed death 1, and TNF-RII, and produced lower concentrations of IL-2 and higher concentrations of IL-10. In a murine model of asthma, an adoptive transfer of Treg-of-B cells before or after immunization sufficiently suppressed Th2 cytokine production and eosinophilic infiltration, and alleviated asthmatic symptoms. B cells isolated from gut-associated lymphoid tissues can generate regulatory T cells that may be important in oral tolerance, and that may be applicable to the alleviation of allergic symptoms.

IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The hallmark of IgAN is underglycosylation in the hinge region of IgA1. Increasing evidence supports the underglycosylated IgA-containing immune-complex including IgG antibodies against the glycans of the hinge region of IgA1 are key factors for mesangial deposition and then trigger inflammation and glomerular injury. The polymeric IgA is produced after aberrant mucosal IgA response. The displacement of mucosal B cells to systemic lymphoid organs and bone marrow may arise from abnormal trafficking of lymphocytes along the mucosa-bone marrow axis involving changes of chemokines and adhesion molecules. This review will summarize the works on the genetics, the mucosal and systemic IgA immune response, mechanism of underglycosylation of IgA1, and the pathological effect of mesangial IgA deposition in IgAN.

Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case.