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Background Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA. Case diagnosis/treatment The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased. Conclusion To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency., Author(s): Mari Okada [sup.1] , Masayuki Nagasawa [sup.1] , Akihiro Oshiba [sup.1] , Hiroyuki Kawaguchi [sup.2] Author Affiliations: (1) grid.416332.1, 0000 0000 9887 307X, Department of Pediatrics, Musashino Red Cross [...]

Mast cells synthesize and secrete specific cytokines and chemokines which play an important role in allergic inflammation. Aggregation of the high-affinity Fc receptor (FceRI) for immunoglobulin E (IgE) in MC/9 mouse mast cells stimulates the synthesis and secretion of tumor necrosis factor [Alpha] (TNF-[Alpha]). Fc[Epsilon]RI aggregation activates several sequential protein kinase pathways, leading to increased activity of extracellular signal-regulated kinases (ERKs), c-Jun amino-terminal kinases (JNKs), and the p38 mitogen-activated protein (MAP) kinase. Inhibition of ERKs with the compound PD 098059 had little effect on Fc[Epsilon]RI-stimulated TNF-[Alpha] production. Aggregation of Fc[Epsilon]RI stimulated MEK kinase 1 (MEKKI) activity, which activates JNK kinase (JNKK), the kinase that phosphorylates and activates JNKs. Expression of activated MEKK1 (AMEKK1) in MC/9 cells strongly stimulated JNK activity but only weakly stimulated p38 activity, and it induced a large activation of TNF-[Alpha] promoter-regulated luciferase gene expression. Inhibitory mutant JNK2 expressed in MC/9 cells significantly blunted Fc[Epsilon]RI stimulation of TNF-[Alpha] promoter-driven luciferase expression. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, diminished Fc[Epsilon]RI-mediated TNF-[Alpha] synthesis, significantly blunted JNK activation and TNF-[Alpha] promoter-driven luciferase expression, and only weakly inhibited p38 kinase activation. Inhibition of NF[Kappa]B activation resulting from [Delta]MEKKI expression or Fc[Epsilon]RI stimulation did not affect TNF-[Alpha] promoter-driven luciferase expression. Our findings define a MEKK-regulated JNK pathway activated by Fc[Epsilon]RI that regulates TNF-[Alpha] production in mast cells.

An eight-year-old girl was admitted for prolonged fever and general fatigue. Bilateral reddened and swollen tonsils covered with white fur and increased numbers of atypical lymphocytes in blood led to a diagnosis of infectious mononucleosis (IM) due to primary Epstein–Barr virus (EBV) infection, which was confirmed by a positive anti-EBV viral capsid antigen IgM antibody reaction. She had a swollen thyroid gland and glycosuria at admission, which persisted after IM resolved. Undetectable thyroid-stimulating hormone (TSH), increased thyroid hormone and elevated HbA1c levels led to a diagnosis of autoimmune polyglandular syndrome type3A, based on the presence of antibodies for TSH receptor and glutamic acid decarboxylase. The clinical significance of EBV infection in the development of autoimmune endocrine disorders has been discussed. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for infectious diseases. However, the relationship between obesity and febrile urinary tract infection (fUTI) is controversial. This study aimed to determine the relationship between obesity and fUTI in young children., Methods: We analyzed the medical records of children aged <2 years who were admitted to our hospital because of fever between April 2013 to March 2018. The children were categorized into three groups of non-obese, overweight, and obese according to the World Health Organization weight-for-length curves for children aged <2 years., Results: A total of 600 patients were enrolled in this study, of whom 118 were diagnosed with first fUTI. Patients in the fUTI group were younger than those in the control group (patients who were diagnosed with other febrile diseases) (5 ± 5.11 vs 11 ± 6.53 months; P < 0.001). There were no significant differences in the populations of overweight and obese children between the fUTI and control groups. In the fUTI group, the duration of fever, types of pathogen, recurrent rate, the grades of vesicoureteral reflux, and renal scarring were not associated with obesity. The white blood cell count and C-reactive protein levels were not significantly different among the three weight-for-length categories. The same results were obtained when the fUTI group was compared with an age-matched control group (n = 192, 4 ± 2.55 months old; P = 0.261)., Conclusions: Obesity is not a significant risk factor for fUTI in febrile hospitalized young children. Our study suggests that conducting urinalysis for febrile young children without obvious sources, irrespective of obesity, should be considered., (© 2021 Japan Pediatric Society.)

We report here that human B cells produce thymus and activation-regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22) if stimulated with anti-CD40 and IL-4. The production was determined by both protein and mRNA level using specific ELISA and semi-quantitative RT-PCR methods. Since the ligand of the TARC and MDC is CCR4, which is specifically expressed on Th2 type T cells, the production of these CC chemokines is likely to play important roles in the T cell and B cell interaction. Consistent with this, ovalbumin (OVA) specific IgE levels, which reflect the T-B cell interaction, are significantly correlated with the amounts of TARC and MDC in sera. Furthermore, we found that TARC and MDC levels are significantly increased in the sera obtained from patients with atopic dermatitis, and that the amounts are correlated with the severity of atopic dermatitis. Since CD40 ligand and IL-4 are produced by activated T helper cells, these results indicate that TARC and MDC produced by B cells play important roles in the production of antigen specific IgE by the T-B cell interaction and in the pathogenesis of allergic disease.