Background and objectives: Translationally controlled tumor protein (TCTP) is widely expressed as housekeeping protein that has various intracellular and extracellular functions including its ability to activate mast cells. Extracellular TCTP has been found in nasal, bronchoalveolar lavage and skin blister fluids and exhibits the capacity to induce histamine release from basophils, suggesting that TCTP plays a role in allergic diseases including asthma, atopic dermatitis and urticaria. Dimerization of TCTP is important for its cytokine-like activity, therefore, we hypothesized that the dimerized TCTP may have an important role by inducing histamine and other mediator release, which may drive development of chronic spontaneous urticaria (CSU) symptoms.
Materials and Methods: One hundred sixteen CSU patients and 70 healthy normal controls (NCs) were enrolled at Ajou University Medical Center, Suwon, South Korea. Serum TCTP levels of study subjects were measured by ELISA and compared according to other CSU-related clinical parameters. Basophil activation test (BAT) was performed by measuring CD203c expression on peripheral basophils from CSU patients. In vitro, β-hexosaminidase release from human mast cell line, monomeric and dimeric TCTP stimulated LAD-2 mast cells was evaluated. Western blot (WB) analysis was performed to detect dimeric TCTP from sera of CSU patients and NCs in non-reducing condition. Rapid dot-blot immunoassay was used for measuring the level of IgG to high affinity Fc epsilon receptor I alpha subunit (FcεRIα) level in serum of CSU patients and NCs.
Results: There was no difference between serum levels of TCTP in CSU patients and NCs. The intensity of dimeric TCTP on WB was visually stronger in CSU patients than in NCs. Severe CSU patients had higher serum TCTP levels (P=0.049) and those having IgG positivity to FcɛRIα (P=0.038). Serum TCTP was significantly positive correlated with eosinophil cationic protein levels (Spearman’s rho 0.341, P=0.001). Both basophil and mast cell degranulation were significantly increased after the stimulation with dimeric TCTP, but, not with monomic TCTP.
Conclusion: The capability of TCTP to activate basophils and mast cells is dependent on its dimerization process, suggesting that the inhibition of TCTP dimerization might have therapeutic benefit for CSU. Association of TCTP levels with the presence of IgG to FcεRIα autoantibody indicating that autoimmune mechanisms of CSU which may related to its dimerization.