Expression Of Inducible Co-stimulator And B7-related Protein-1on Lymphocytes In Peripheral Blood From The Patients With Lupus Nephritis And Influence Of Dexamethasone

Objective To study the expression of inducible co-stimulator(ICOS) on T lymphocytes and B7-related protein-1 (B7RP-1) on B lymphocytes in patients with lupus nephritis (LN), patients without lupus nephritis(nLN) and normal control, and to explore their relationship with disease activity and influence of dexamethasone.Methods Systemic lupus erythematosus (SLE )patients were in- and out- patients of the Rheumatology and Nephropathy Department in the Anhui Provincial Hospital, health volunteers were recruited as controls, LN patients, nLN patients and normal controls were age- and sex- matched. Patients'major clinical characteristic, laboratory indice were collected by self-designed questionnaire containing systemic lupus erythematosus disease activity index(SLEDAI). Three–color immunofluorescent staining and flow cytometric assay were used to analyze the level of ICOS expression on T lymphocytes and B7RP-1 expression on B lymphocyte types in peripheral blood from 20 LN patients, 20 nLN patients and 20 healthy volunteers. Lymphocytes isolated from patients'peripheral blood were co-cultured with proper dexamethasone to find influence of dexamethasone on the expression of ICOS and B7RP-1.Results The expression of ICOS on CD4+CD45RO+ and CD8+CD45RO+ T lymphocytes from LN and nLN patients was higher than that from normal controls, and the expression of ICOS from LN patients was higher than that from nLN patients(CD4:F=28.10,P<0.05 ; CD8:F=20.87,P<0.05),but the level of ICOS had no correlation with SLEDAI(CD4: r=0.16,P>0.05 ; CD8: r=0.26,P >0.05). The frequency of plasma cell in B lymphocytes from LN and nLN patients was markedly higher than that from normal controls, and there was significant difference between LN and nLN patients(F =46.59,P <0.05). The frequency of memory B lymphocytes from LN and nLN patients was lower than that from normal controls, but no significant difference between LN and nLN patients were found(F =6.40,P <0.05).Regarding the frequency of na?ve B lymphocytes, there was no significant difference among three groups. The level of B7RP-1expression on B lymphocytes from LN and nLN patients was lower than that from normal controls(F =30.02,P <0.05), but no significant was found between LN and nLN patients, and no correlation was found between the level of B7RP-1 expression and SLEDAI(r=0.04,P>0.05). Lymphocytes isolated from peripheral blood were co-cultured with proper dexamethasone, the expression of ICOS on T Lymphocytes(CD4:F =11.94,P <0.05;CD8: F =34.41,P <0.05) and B7RP-1 on B Lymphocytes (F =16.12, P <0.05) were down-regulated.Conclusions The level of ICOS on T lymphocytes in LN patients increase, and the level of B7RP-1 on B lymphocytes decrease, indicating that ICOS /B7RP-1 pathway may play a primary role in the pathogenesis of SLE especially in the onset LN. Dexamethasone significantly down-regulate the expression of ICOS and B7RP-1.Therefore therapeutic effect of dexamethasone may be partly attributed to its inhibition of ICOS and B7RP-1 expression.