The Role of Translationally Controlled Tumor Protein in Chronic Spontaneous Urticaria

RATIONALE: Translationally controlled tumor protein (TCTP), known as histamine releasing factor (HRF) has ability to activate mast cells. To investigate the role of TCTP in the pathogenesis of CSU, we measured serum TCTP levels and mast cell degranulation and basophil activation tests with monomer and dimer TCTP.

METHODS: TCTP level was measured by ELISA in the sera from 116 CSU patients and 70 healthy controls (NCs). CD203c expression on peripheral basophils from CSU patients and β-hexosaminidase release from LAD2 cells were measured upon to monomer and dimer TCTP. Non-reducing western blot (WB) analysis was used to detect dimerized TCTP

RESULTS: No difference was observed in serum TCTP levels between CSU patients and NCs. However, dimerized TCTP intensity was stronger in CSU patients compared with NCs in WB. TCTP levels were significantly higher in patients with severe CSU (51.1±31.6 vs 44.6±45.6 ng/ml, P=0.049) and a positive IgG to FceRIa (60.4±49.8 vs 42.5±37.6 ng/ml, P=0.038). A positive correlation was observed between TCTP and eosinophil cationic protein (ECP) levels (Spearman’s rho 0.341, P=0.001). Both basophil activation and mast cell degranulation were significantly increased after stimulation with dimerized TCTP (P<0.01), but not with the monomers.

CONCLUSIONS: The ability of TCTP to activate basophil and mast cells is dependent on dimerazation, suggesting inhibition of TCTP dimerization can be a therapeutic option for CSU. Significant associations of TCTP levels with urticaria severity, ECP, and the presence of IgG to FcεRIα in CSU patients indicating autoimmune mechanisms can be involved in the dimerization of TCTP, influence histamine release and cytokine-like activity