An Investigation On Glucocorticoid Receptor In Peripheral Blood Mononuclear Cells From Patients With Myasthenia Gravis

Objective Myasthenia gravis(MG) is an autoimmune disease. Acetylcholine receptor(AChR) is illness-specific antigen. Humoral and cellular immune responses, and cytokine secretion are abnormal in MG. IFN — γ is one of important indirect pathogenic factors. Glucocorticoids(GC) are potent immunosuppressive agents, and are clinically used in the treatment of MG. It is well known that giucocorticoid action is mediated through high affinity binding of GC to the giucocorticoid receptor(GR). Clinically, individuals have different responsiveness to GC. It is necessary to explore the function of GR and its relations to GC efficacy in MG. Although there have been a few reports about GR in MG patients, no detailed data about the relations between GR and GC efficacy were given in the literatures. The mechanism about the alteration of GR in MG is still unknown. This study aims at evaluating the relations between GR and GC efficacy in MG patients. In order to obtain the direct information on the sensitivity of MG patients to GC and to test the reliability of GR prediction to GC efficacy, the relations between GR numbers and in vitro responsiveness of PBMC in MG patients to dexamethansone are analyzed. By detecting the effect of AChR or IFN- γ on GR and GRmRNA of PBMC in patients, this study attempts to clarify the relationship between the GR alteration and the disease, and to discern the possible mechanism of the abnormality of PBMC GR in MG patients.Materials and Methods ~3H-dexamethansone radioligand-binding assay and Scatchard analysis were used to measure the number of GR and dissociation constant(Kd) in PBMC from 193 MG patients, 10 patients with other neuroimmunological disorders, 66 with cerebral vascular disorders(CVD) and 35 healthy donors. In 30 MG patients with GC pulse treatment, the efficacy of GC after one-month and 6 month treatment was assessed according to relative clinical score. In 24 MG patients, GR numbers were monitored at 1, 2, 3, 4 weeks, 2, 3, 6 months after GC treatment. Simultaneous detection of GR numbers and lymphocyte proliferation assay (~3H-TdR incorporation) was carried out in 10 MG patients and 10 healthy...