Memory B cells (B cells) are the basis of long-lasting humoral immunity. They respond to re-encountered antigens by rapidly producing specific antibodies and forming germinal centers (GCs), a recall response that has been known for decades but remains poorly understood. We found that the receptor for the cytokine IL-9 (IL-9R) was induced selectively on B cells after primary immunization and that IL-9R-deficient mice exhibited a normal primary antibody response but impaired recall antibody responses, with attenuated population expansion and plasma-cell differentiation of B cells. In contrast, there was augmented GC formation, possibly due to defective downregulation of the ligand for the co-stimulatory receptor ICOS on B cells. A fraction of B cells produced IL-9. These findings indicate that IL-9R signaling in B cells regulates humoral recall responses.
We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light-coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.
Our findings indicate that the efficacy of the ICG test is comparable to direct microscopy for the detection of dermatophytes. Performance of the assay was easy, and results were available quickly. We suggest that it is an effective tool for dermatophytosis screening.
Psoriasis, though not an immediately life‐threatening disorder, still lowers quality of life and disrupts daily functions. While many treatments for psoriasis exist, few are convenient and safe long term; even if sufficiently effective, treatments themselves often decrease quality of life and make long‐term treatment adherence difficult. Approved in Japan in December 2016, apremilast was expected to function as a simple, long‐term, systemic therapeutic agent for psoriasis. We report on the clinical outcomes of administrating apremilast for 2 years as observed in 46 psoriatic patients at the Saruwatari Dermatology Clinic between March 2017 and February 2019. We believe the ease of clinic consultation (as compared with large general hospital consultation) draws patients who are busy or have mild symptoms, and consequently poor adherence to regular visits and treatment, reflecting realistic conditions. Major adverse events with apremilast treatment were diarrhea (37.0%) and nausea (15.3%), with most cases of diarrhea being mild. Drug survival analysis by the Kaplan–Meier method revealed a 1‐year continuation rate of 46.8% and a 2‐year continuation rate of 37.4%. Dermatology Life Quality Index (DLQI) scores during the observation period declined from 9.3 to 2.8 (P < 0.0001) on average, with the DLQI‐0/1 achievement rate being 28.6%. Based on our findings, we conclude that apremilast is suitable as a long‐lasting basic treatment that is easy to prescribe in small clinics and easy to use in everyday life.
A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non-consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G-to-A point-mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A-to-G point-mutation 4 bases from the 3" terminus of intron 4 that led to the in-frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3-48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3-48. The allelic frequency of IVS3-48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).
Trichothiodystrophy group A (TTD-A) is one of the three types of photosensitive TTD and is a very rare genodermatosis with deficient post-ultraviolet (UV) DNA repair. We herein describe the first Japanese case with a novel mutation in the GTF2H5 gene responsible for TTD-A. A 5-year-old male, born as a collodion baby from healthy non-consanguineous parents, exhibited sun sensitivity, brittle hair, ichthyosis, cataracts and mental/physical retardation. He demonstrated neither neurological abnormalities nor pigmentary changes following sun exposure. The patient's primary fibroblasts were hypersensitive to killing by UV (D 0 = 1.5 J/m 2 ), and the post-UV unscheduled DNA synthesis was 13% of normal. A host cell reactivation complementation analysis showed a decreased DNA capacity without recovery after transfecting any xeroderma pigmentosum genes. We identified a novel homozygous mutation (c.166G>T) in the coding region of the GTF2H5 gene that resulted in a predicted amino acid change: p.E55X. Thus far, only one Japanese case of TTD with a mutation of the XPD gene had been reported. The present case is the first of TTD-A and the second case of TTD in Japan, suggesting that it is necessary to differentiate TTD from other photosensitive disorders, although the incidence of TTD is very low in Japan compared to that observed in Western countries.
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