Correlation of Circulating Glucocorticoid-Induced TNFR-Related Protein Ligand Levels with Disease Activity in Patients with Systemic Lupus Erythematosus
The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3？ng/mL and 36.59？ng/mL, resp.; ). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3？ng/mL and 136.3？ng/mL, resp; ) as well as normal controls (36.59？ng/mL; ). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations. 1. Introduction Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by the production of various autoantibodies that cause damage to multiple organs involving the skin, joints, heart, lungs, kidneys, and central nervous system (CNS) [1]. However, the precise etiology remains unclear. SLE is characterized by hyper-reactivity of B lymphocytes, hyper-gammaglobulinemia, circulating immune complexes, and production of organ-specific and non-organ-specific autoantibodies. Moreover, dysregulated cellular immune responses are at times featured as lymphopenia and monocytosis. Numerous studies have shown that both T-cell activation and proinflammatory cytokine production are critically involved in SLE pathogenesis. Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a type I transmembrane protein belonging to the TNFR superfamily, and its cytoplasmic domain shares strong homology with a subgroup of the TNFR superfamily lacking the death domain, including CD27, CD134 (OX40), and CD137 (4-1BB). GITR is expressed predominantly on CD4+CD25+ regulatory T cells at high levels [2–4]. Moreover, other cells with regulatory activity, such as CD4+CD25？, CD8+CD25+, and CD8+CD28？ cells, express GITR at high levels [5]. However, its expression has also been detected on many cell types of both
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