Transglutaminase 2 expressed in mast cells recruited into skin or bone marrow induces the development of pediatric mastocytosis.

BACKGROUND: Mastocytosis is characterized by a pathological increase in mast cells in organs such as skin and bone marrow. Transglutaminase 2 (TG2) expressed in mast cells contributes to allergic diseases, but its role in mastocytosis has not been investigated. This study aimed to investigate whether TG2 contributes to pediatric mastocytosis. METHODS: Serum, various skin tissues or bone marrow (BM) biopsy and aspirates were obtained from pediatric normal control or patients with indolent systemic mastocytosis (SM), mastocytoma, and urticaria pigmentosa (UP). Tryptase, individual cytokines, leukotriene C4 (LTC4 ), and TG2 activity in the serum were determined by enzyme-linked immunosorbent assay, mast cell population by May-Grünwald-Giemsa, CD 117 by immunofluorescence, cell surface molecules by Western blot, and colocalization of c-kit and TG2 or IL-10-expressing cells, CD25, and FOXP3 by immunohistochemistry. RESULTS: Infiltration of CD25(+) CD117(+) CD2(-) mast cells into BM and scalp/trunk/ear dermis; expression of FcεRI, tryptase, c-kit, FOXP3, CCL2/CCR2, and vascular cell adhesion molecule-1; and colocalization of c-kit and TG2 were enhanced in patient's skin tissues or BM, particularly SM, but colocalization of c-kit and IL-10-expressing cells was decreased vs. normal tissues. Amounts of LTC4 and inflammatory cytokines, expression of tryptase or TG2 activity were increased in patient's serum, BM aspirates, or ear/scalp skin tissues, respectively, vs. normal persons, but IL-10 level was decreased. CONCLUSION: The data suggest that mast cells, recruited in the skin and BM by CCL2/CCR, may induce the development of pediatric mastocytosis through reducing IL-10 due to upregulating TG2 activity via transcription factor nuclear factor-κB. Thus, TG2 may be used in diagnosis of pediatric mastocytosis, particularly SM.

A nationwide study of acne treatment patterns in Korea: analysis of patient preconceived notions and dermatologist suggestion for treatment.

Patients often have preconceived notions about acne treatments before visiting dermatologists. The aim of this study was to explore the association between patients' beliefs regarding acne and physicians' suggestion for treatment modality in dermatology clinics. A cross-sectional, nationwide multicentre study was conducted. A total of 1,370 patients completed questionnaires about beliefs about acne treatment before seeking medical care, and 101 dermatologists assessed their acne severity and proposed treatment methods. We found that patients had preconceptions in understanding disease characteristics, assessing subjective acne severity and preferring specific treatment modalities. Dermatologists' determination of topical agents as first-line treatment was affected by disease severity and patients' preferences. They were also more likely to prescribe isotretinoin even in moderate acne compared to oral antibiotics and topical agents. Selections of physical treatments and light-based therapies were affected by patients' preferences, subjective self-evaluation and dermatologists' assessments. Thus, we suggest that acne treatment strategies should incorporate both patients' subjective perceptions and objective clinical practices into a management paradigm.

A novel function of Siglec-9 A391C polymorphism on T cell receptor signaling.

BACKGROUND: Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are the best-characterized immunoglobulin-type lectins. There is a growing amount of data linking Siglec and autoimmune diseases. The recently identified Siglec-9 inhibits T cell receptor (TCR)-mediated signaling which has been demonstrated by site-directed mutagenesis. In human Siglec-9, at least 8 nonsynonymous SNPs have been detected without functional studies. This study examined the SNP(s) related to TCR-mediated signaling. METHODS: Since the functions of Siglecs are modulated by their interaction with sialic-acid-containing carbohydrate groups, a molecular modeling analysis of carbohydrate binding interactions and an RBC binding analysis were performed using the 8 SNPs. The TCR-mediated signaling was analyzed with the downstream signaling molecules ZAP-70 and IL-2. RESULTS: This study revealed that an A391C polymorphism is the only mutant related to the binding. Jurkat T cells transfected with the A391C mutant reduced the inhibition of ZAP-70 phosphorylation and IL-2 production compared to cells transfected with the wild type. CONCLUSIONS: Siglec-9 A391C was the only polymorphism related to TCR-mediated signaling in human Siglec-9, resulting in less inhibition compared to the wild type.

Control of palmar hyperhidrosis with a new "dry-type" iontophoretic device.

BACKGROUND: Palmar hyperhidrosis is characterized by excessive sweating on the palm, and among the various treatment modalities, tap water iontophoresis has been widely used. OBJECTIVE: The objective of this study was to assess the effect of a new "dry-type" iontophoretic device that was locally manufactured and did not use tap water to control sweating. METHODS: Ten subjects with palmar hyperhidrosis were enrolled in this study. To be treated the patients were instructed that they only have to grasp the device. Only one palm was treated for 2 weeks, and then the treatment was discontinued the following next 2 weeks. The other palm was not treated as a control. At the end of second week, biopsy specimens were obtained from untreated and treated palm, respectively, and examined histologically. RESULTS: Nine of 10 patients were satisfied with this therapy reducing their sweat outputs from 33% to 51% of baseline at the end of 2 weeks' treatment, and after 2 weeks of discontinuation of treatment sweat productions returned to near baseline. The pathologic examinations showed some occlusions and destruction of intraepithelial eccrine ducts only in the treated palm. CONCLUSION: We suggest that dry-type iontophoresis could reduce palmar sweating more conveniently than other conventional methods.