Serum And Intrarenal Expression Of B Lymphocyte Stimulator And BR3in Lupus Nephritis Patients And The Effect Of Glucocorticoid On Them

Background and ObjectiveSystemic lupus erythematosus(SLE) is a chronic, multisystem autoimmune disorder and95%of them have lupus nephritis(LN). B lymphocyte stimulator(BlyS), a member ofthe TNF superfamily, is a prominent factor in B cell survival、proliferation、developmentand differentiation. BlyS can bind to three receptors, BlyS receptor3(BR3) is the majordriver that mediate BlyS dependent B cell signals. For the past many years, it hasdemonstrated that the high expression of BlyS can lead to the onset of SLE-like diseases.Animal studies and phase I、II、III clinical trials has definitely proved the safety andefficacy of it’s antagonist Blimumab which has been approved for the treatment of lupusin American. There are no detailed data on the local renal expression of BlyS and it’sreceptor BR3in human LN patients, therefore, to determine the role of BlyS and BR3on SLE and LN, we examined the serum concentration of BlyS and localized theintrarenal expression of BlyS and BR3in LN patients.Besides, the price of the new drugis high and it may restrict its apply, so we examined the effect of glucocorticoid on theserum and intrarenal expression of BlyS in LN patients.Methods63SLE patients were inpatients in Nephrology Department of the First Hospital ofAnhui Medical University from June,2010to July,2011.55of them were clearlydiagnosed lupus nephritis by renal biopsy, including6LN III,24LN IV and7LN Vaccording to the classification standard of International Society Nephrology(ISN)/ Renal Pathology Society(RPS).(1)63SLE patients were signed as SLE group and7health examination people were signed as normal controls. The serum concentration ofBlyS、TNF-α and IL-1in the two groups were detected by ELISA, then the differencesbetween this two groups were compared. The association of the above-mentioned threeindex in SLE group were analyzed. The association between these three index and SLEdisease activity index(SLEDAI)、the concentration of anti-dsDNA and the titer ofanti-nuclear antibody(ANA) in SLE group were also analyzed.(2)37LN patients weresigned as LN group and10renal tissues which is non-renal glomerular disease weresigned as normal controls. The intrarenal expression location and level of BlyS and BR3in the two groups were detected by immunohistochemistry, then the differences betweenthis two groups were compared. The association between the two above-mentionedindex and the classification of LN were analyzed.(3) The LN patients that haven’treceived any treatment(n=13) or received glucocorticoid therapy more than2weeks(n=12) were selected from37LN patients. They were divide into two groupsaccording to the time of prednisone therapy. The effect of glucocorticoid therapy on theSLEDAI、serum and intrarenal expression of BlyS and BR3、the concentration ofanti-dsDNA、the titer of ANA were analyzed.Results(1) The serum concentration of BlyS、TNF-α and IL-1in63SLE patients wasobviously higher than that in7normal controls(P<0.001). There were positivecorrelation between the serum concentration of BlyS and TNF-α(r=0.70, P<0.001) inSLE group. No statistically significant correlation could be found between the levels ofBlyS、TNF-α、IL-1and SLE Disease Activity Index (SLEDAI), the concentration ofanti-dsDNA antibody and the titer of ANA, immunoglobulin(Ig)G、IgA、IgM、C3、C4、proteinuria、the count of white blood cells and thrombocytes(P>0.05).(2) Intermediate-intensity staining of BlyS was detected in renal tubules in normal-appearing renal tissues, however, both renal tubules and infiltrating cells havethe ability to produce BlyS in LN patients. All of the normal-appearing renal tissueswere negative for BR3, and it was restricted to a small population of infiltrating cells inrenal tissues of LN patients. The intrarenal production of BlyS in LN patients wasobviously higher than that in normal-appearing renal tissues, and the expression levelsof BlyS in LN IV and V were higher than that in LN III(P=0.04，0.02), although therewas no statistically significant difference between LN IV and V(P=0.31),we can see arise trend in the expression levels of BlyS.(3) The intrarenal production of BlyS and SLEDAI scores in LN patients that receivedglucocorticoid therapy more than2weeks were obviously lower than that in LN patientsthat haven’t received any treatment(P=0.012,0.005).ConclusionThe serum and intrarenal expression level of BlyS in SLE patients are obviouslyincreased,and the change of BlyS expression level is associated with the classificationof LN. The effect of glucocorticoid therapy on disease activity in LN patients mayassociate with the expression level of decreasing intrarenal BlyS.