Abstract
High serum concentrations of thymus and activation-regulated chemokine (TARC) are observed in allergic diseases such as atopic dermatitis and bronchial asthma. Frequent allergic symptoms have been reported in patients with IgG4-related disease (IgG4-RD). We investigated the pathogenic role of TARC as a biomarker in IgG4-RD patients. We evaluated the serum concentrations of TARC from 29 IgG4-RD patients, 28 primary Sjögren syndrome (pSS) patients, and 23 healthy controls (HCs) by enzyme-linked immunosorbent assay (ELISA). We analyzed the correlations between the TARC concentrations and the subjects’ clinical parameters. To investigate the biological effect of TARC on the pathogenesis of IgG4-RD, we evaluated the in vitro induction of plasmablasts from IgG4-RD patients by TARC. The serum concentrations of TARC in the IgG4-RD patients were significantly higher than those of the pSS patients and HCs. The serum TARC concentration of the IgG4-RD group was positively correlated with the IgG4-RD responder index (IgG4-RD RI) score and with the number of organs involved, but it was not correlated with the serum IgG4 level or eosinophil number in the IgG4-RD patients’ peripheral blood. The patients who had lung involvement had higher serum TARC concentrations. In vitro, TARC clearly induced the formation of plasmablasts from the IgG4-RD patients’ peripheral blood mononuclear cells. Collectively, our data suggest that a systemic increment of TARC may contribute to the development of IgG4-RD through an aberrant induction of plasmablasts.
Highlights
TARC, known as C-C Motif chemokine ligand 17 (CCL17), is expressed in the thymus and is produced by dendritic cells, endothelial cells, keratinocytes, and fibroblasts[1]
The Enzyme-linked immunosorbent assay (ELISA) revealed that the serum concentrations of TARC were significantly higher in the Immunoglobulin G4-related disease (IgG4-RD) group than those of the primary Sjögren syndrome (pSS) and healthy controls (HCs) groups at mean 121.3 pg/ml and 254.2 pg/ml, respectively (Fig. 1A)
To investigate the usefulness of the serum concentration of TARC for the diagnosis of IgG4-RD, we generated receiver operating characteristics (ROC) curves for TARC to distinguish the patients with IgG4-RD from HCs or the patients with pSS
Summary
TARC (thymus and activation-regulated chemokine), known as C-C Motif chemokine ligand 17 (CCL17), is expressed in the thymus and is produced by dendritic cells, endothelial cells, keratinocytes, and fibroblasts[1]. High serum concentrations of TARC are observed in patients with atopic dermatitis, and its concentration is closely related to disease activity[1,5]. The concentration of TARC is reported to be elevated in serum and in sputum of patients with bronchial asthma[7]. The blockade of the TARC/CCR4 axis by using anti-TARC antibodies and anti-CCR4 antibodies was reported to attenuate airway inflammation in a murine model of asthma[9,10]. In light of these reports, TARC has been suspected to be involved in the pathogenesis of allergic diseases, and TARC may have potential as a therapeutic target. The numbers of Th2 cells in peripheral blood were increased in IgG4-RD patients who had concomitant allergic diseases[19]
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