Clinical Research Of Glucocorticoid Receptor-α And Glucocorticoid Receptor-β In The Patients With Rheumatoid Arthritis

BackgroundRheumatoid arthritis(RA) is a systemic autoimmune disease.It is characterized by joint inflammation and synoviocyte proliferation,which always lead to joint destruction and joint deformation eventually.Early diagnosis and therapy are very important to RA patients.Glucocorticoid(GC) is a very important drug to treat RA.Its anti-inflammatory/immunosuppressive actions can relieve clinical symptoms and decrease the rate of erosive progression of the disease,so it is widely used in RA patients. But some patients does not respond to GC therapy and has been classified as glucocorticoid resistance.GC's actions is mediated by an intracellular receptor called glucocorticoid receptor(GR).GR has two subtypes,GR-αand GR-β.GR-αis the classical GR which mediates most GC actions;GR-βcan not mediate GC actions and can suppress the action of GR-α,so it may be related to cortico resistant.Moreover, some proinflammatory factors such as TNF-αcan upregulate the expression of GR(especially GR-β).Because TNF-αplay a core role in RA,it leads to hypothesis that the abnomal level of GR may participate in the pathogenesis of RA.ObjectiveTo detect the expression of GR-αand GR-βmRNA in peripheral blood mononuclear cells(PBMC) in the patients with active RA patients,relieved RA patients, OA patients and healthy control cases,respectively;To explore the role of GR in the pathogenesis and progression of RA and investigate the relationship between the expression of GR and common clinical indices(ESR,CRP,RF) of RA.MethodsWe selected 44 patients with rheumatoid arthritis,15 patients with osteoarthritis(OA) and 20 Healthy volunteers from Oct 2006 to Mar 2007.According to respective inclusive and exclusive standards,RA patients were divided into two groups:24 patients in active RA group and 20 patients in relieved RA group.Total RNA was isolated from PBMCs and reversely transcribed into cDNA.The Real time fluorescence quantitative polymerase chain reaction(RT- FQ-PCR) was used to examine the level of GRαand GRβmRNA.The level of ESR,CRP and RF was detected at the same time.ResultsThe level of both GR-αand GR-βmRNA in RA group were significantly higher than those in controls(P＜0.01);The level of GRβmRNA in active RA group was significantly higher than that in relieved RA group(P＜0.01);The level of GR-αmRNA in active RA group had no difference with that in relieved RA group (P＞0.05);The expression of GR-βfrom RA was positively associated with CRP(P=0.01),but it had no relationship with ESR and RF;The level of GR-αwas not associated with CRP,ESR and RF.ConclusionsRT-FQ-PCR is a sensitive,specific and reproducible method for detecting mRNA;GR-αand GR-βmay be involved in the pathogenesis and development of RA. GRβmay be positively associated with severity of RA;The more Severity of RA,the more resistance to GC therapy.