Dimerized, Not Monomeric, Translationally Controlled Tumor Protein Induces Basophil Activation and Mast Cell Degranulation in Chronic Urticaria

Translationally controlled tumor protein (TCTP) is also known as histamine releasing factor as it has the ability to activate mast cells. To investigate the role of TCTP in the pathogenesis of chronic spontaneous urticaria (CSU), we evaluated serum level of TCTP and effect of TCTP on basophil and mast cell degranulation. TCTP levels in the sera from 116 CSU patients and 70 normal healthy controls (NCs) were measured by ELISA. CD203c expression on basophils from CSU patients and β-hexosaminidase release from Laboratory of Allergic Disease 2 mast cells were measured upon stimulation monomeric and dimeric TCTP. Non-reducing Western blot analysis was used for detecting dimeric TCTP. No difference was observed in serum TCTP levels between CSU patients and NCs (p=0.676). However, dimeric TCTP intensity on Western blot was stronger in CSU patients than in NCs. TCTP levels were higher in patients with severe CSU (p=0.049) and with IgG positivity to FcɛRIα (p=0.038). A significant positive correlation was observed between TCTP and eosinophil cationic protein levels (Spearman's rho=0.341; p=0.001). Both basophil and mast cell degranulation were significantly increased after stimulation with dimeric TCTP, but not with monomic TCTP. The ability of TCTP to activate basophil and mast cells is dependent on dimerization, suggesting that the inhibition of TCTP dimerization can be a therapeutic option for CSU. Association between TCTP levels and the presence of IgG to high affinity Fc epsilon receptor I alpha subunit in CSU patients indicates that autoimmune mechanisms may be involved in the dimerization of TCTP.

Anti-TPO IgE Autoantibody in Chronic Urticaria: Is It Clinically Relevant?

No abstract available.

Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma

PURPOSE: Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms. METHODS: A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each). CONCLUSIONS: These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.