title: Increased chemokine (C-C motif) ligand 21 expression and its correlation with osteopontin in Graves' disease.
abstract: Graves' disease (GD) is a chronic autoimmune process characterized by the production of auto-antibodies that presumably consequent to the lymphocytic infiltrates in the thyroid. Chemokine (C-C motif) ligand 21 (CCL21) is important for the circulation of CC-chemokine receptor 7 (CCR7)-expressing cells. Meanwhile, osteopontin (OPN) enhances the production of proinflammatory cytokines and chemokines through NF-κB and MAPK signaling pathways in GD. Although CCL21 has been reported to play a vital role in several autoimmune diseases, little is known about the relationship between CCL21 and GD development. This study aimed to detect the CCL21 level in GD and to examine the role of OPN in regulating CCL21 production. 40 initial GD patients, 15 euthyroid GD patients, 12 TRAb-negative GD patients, and 25 healthy control donors were recruited. CCL21 levels in plasma and culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). CD4+ T cells were isolated from peripheral blood mononuclear cells using antibody-coated magnetic beads. Quantitative polymerase chain reaction was used to determine CCL21 expression levels in CD4+ T cells. We demonstrated for the first time that plasma CCL21 levels were overexpressed in GD patients and recovered in TRAb-negative GD patients. Moreover, CCL21 levels correlated with TRAb levels and plasma OPN concentrations. Furthermore, we demonstrated that recombinant OPN increased the expression of CCL21 in a dose- and time-dependent manner. These data indicated a clinical correlation between plasma CCL21 levels and GD. CCL21 could serve as a novel biomarker for GD as well as a potential target for TRAb-positive GD treatment.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Huang
authors.forename: Dongping
authors.initials: D
authors.lastname: Lin
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D054421:Chemokine CCL21 / Q000097:blood*; D005260:Female; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood* / Q000494:pharmacology; D011994:Recombinant Proteins
chemical_list: C515478:CCL21 protein, human; D054421:Chemokine CCL21; D018828:Immunoglobulins, Thyroid-Stimulating; D011994:Recombinant Proteins; C094372:thyrotropin-binding inhibitory immunoglobulin; D053495:Osteopontin