Association of TG2 from mast cells and chronic spontaneous urticaria pathogenesis.
Mast cells and their mediators play important roles in chronic spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed in activated mast cells and contributes to airway inflammation in allergic asthma.



To investigate the role of TG2 in CSU.



Patients with CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived human mast cells and peripheral blood-derived human mast cells were activated with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene C4, and cytokines, were measured in serum or supernatant from cultured mast cells by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was determined in skin tissues by immunofluorescence.



TG2 activity was significantly higher in serum samples from patients with CSU than in serum samples from healthy controls (P < .001). Colocalization of mast cell surface marker c-kit and TG2 was significantly increased in the lesional skin of patients with CSU compared with that in healthy controls. The levels of histamine, leukotriene C4, tumor necrosis factor α, transforming growth factor β, and interleukins 4, 5, and 6 were significantly higher in patients with CSU than in healthy controls (P < .001). Serum TG2 levels had positive correlations with each inflammatory mediator (P < .001). TG2 activity was increased in cord blood-derived human mast cells (CBMCs) and peripheral blood-derived human mast cells activated with IgE compared with those without activation (P < .05).



Our findings suggest that TG2 expressed in and released from mast cells plays an important role in CSU pathogenesis.
Department of Pharmacology and SBRI, Sungkyunkwan University School of Medicine, Suwon, Korea.
Gwan Ui
GU
Hong
Department of Pharmacology and SBRI, Sungkyunkwan University School of Medicine, Suwon, Korea.
Jai Youl
JY
Ro
Department of Dermatology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
Youin
Y
Bae
Department of Dermatology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
In-Ho
IH
Kwon
Department of Dermatology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
Gyeong-Hun
GH
Park
Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
Young Hee
YH
Choi
Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea. Electronic address: mdqueen@hallym.or.kr.
Jeong-Hee
JH
Choi
D000328:Adult; D016207:Cytokines / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood / Q000378:metabolism*; D006632:Histamine / Q000097:blood; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D017997:Leukotriene C4 / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012867:Skin / Q000166:cytology; D012882:Skin Tests; D011503:Transglutaminases / Q000097:blood / Q000378:metabolism*; D014581:Urticaria / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
D016207:Cytokines; D017997:Leukotriene C4; D007073:Immunoglobulin E; D006632:Histamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins