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404. Release of transglutaminase 2 from mast cells may be involved in the pathogenesis of chronic urticaria

Choi, Jeong-Hee; Hong, Gwan Ui; Kwon, In-Ho; Park, Gyeong-Hun; Bae, Youin; Ye, Young-Min; Ro, Jai Youl
Department of Allergy & Clinical Immunology, Ajou University School of Medicine
RATIONALE: Mast cells and its mediators play an important role in the pathogenesis of chronic urticaria (CU). Transglutaminase 2 (TG2) has been reported to be expressed in mast cells and to contribute to allergic asthma. The aim of this study is to investigate the role of TG2 in CU and the source of TG2 in urticarial skin tissues.
METHODS: Seventy two CU patients and control subjects (52 normal controls, 9 acute urticaria and 11 bronchial asthma) were included. Skin biopsies were obtained from 5 CU and 2 normal controls. TG2 activity and inflammatory cytokines such as TNF-, TGF-β, IL-4, IL-5, IL-6, and IL-13 were measured in serum by ELISA. Co-localization of mast cells and TG2 were determined by immunohistochemistry. Peripheral blood-derived human mast cells were activated with anti-IgE, and TG2 activity were measured in the supernatant by ELISA.
RESULTS: TG2 activity was significantly higher in sera of CU patients than normal controls (P < 0.05), while TG2 activity in asthmatics was significantly higher than CU patients (P < 0.05). Co-localization of mast cell surface marker c-kit and TG2 were significantly increased in wheals of CU patients comparing with normal controls. The levels of TNF-, TGF-β, IL-4, IL-5, IL-6, and IL-13 were significantly higher in CU patients than normal controls (P < 0.001, respectively), however, the levels of cytokines were significantly higher in asthmatics than in CU (P < 0.05, respectively). TG2 activity was significantly higher in PBMCs with IgE activation than PBMCs without activation (P <0.05).
CONCLUSIONS: TG2 released from mast cells play a role in the pathogenesis of CU. We also demonstrated that other inflammatory cells are activated in CU showing increased levels of various cytokines. However, the inflammation in CU does not seem stronger than in bronchial asthma.
transglutaminase 2urticariamast cellscytokines
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