ABSTRACT
ObjectiveTo determine whether there is correlation between the pathological classification and urinary level of transforming growth factor(TGF)-β1,macrophage inflammatory protein (MIP)-1α,and Neutrophil gelatinase-associated lipocalin (NGAL) of lupus nephritis.MethodsELISA was used to test the levels of urinary level of TGF-β1,MIP-lα and NGAL.The correlation between these three urinary markers and the pathological classifications,Austin score,histological semi-quantitative score and clinical data were analyzed.Comparisons between groups were performed with t-test,ANOVA and X2 test.Correlation analysis was performed with Pearson analysis.Results①There was significant difference in urinary TGF- β1,MIP1α,and NGAL levels when compared the lupus nephritis group,SLE patients without renal damage group and the normal control group [TGF-β1(351±219),(92±60),(74±29) pg/ml],[MIP-1α(18.0±15.5),(8.5±2.3),(7.1±1.9) pg/ml],[NGAL (1.104±0.519),(0.181±0.030),(0.146±0.024) ng/ml],while there was no significant difference between lupus nephritis (LN) group and patients with other glomerulonephritis.② There was significant difference in the three urinary markers when stratified the LN patients based on the pathological classifications,however,there was no significant difference between the LN group and other glomerulonephritis group.③ Analysis of the correlation between the three urinary markers and semiquantitative histopathological score of the LN patients showed that the urinary level of TGF-β1 and MsMI,GCI,TCI,VCI was closely related to each other,the urinary MIP-1α was related to and endol,and the dGAI and VCI was closely related, while the urinary NGAL was closely related with endol,dGAI and MsHI.The correlation analysis between the three urinary markers and acute and chronic pathological index score of the LN patients showed that TGF- β1 was correlated with the chronic index(r=0.89,P＜0.01 ),the MIP-lα and NGAL were significantly correlated with the activity index(r=0.71,P＜0.01 ; r=0.60,P＜0.01 ).Conclusion There is a positive correlation between the urine TGF-β1 level and chronic kidney disease.The urinary MIP-lαand NGAL are associated with active renal damage.
ABSTRACT
Objective To assess the association of synovial cyclic citrullinated peptide(CCP)expression with T helper 17(Th17) cells/Regulatory T cells (Treg) imbalance,the histological and clinical features of synovitis in rheumatoid arthritis (RA).Methods CCP expression in synovial specimens from 39 patients with RA and 35 controls was detected by immunohistochemistry assay(IH) using 6×His tagged anti-CCP single chain fragment V (ScFv) antibodies,which were generated by pHEN2 phagemid recombinant antibodies display system.The frequencies of Th17/Treg cells in the peripheral blood mononuclear cells (PBMCs) were determined by flow cytometry (FCM).Th17/Treg cells associated cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA).The histological scores and clinical features of synovitis were included in the study.Chi-square test and ANOVA were used for statistical analysis.Results ① The prevalences of synovial C CP expression were significantly different between RA group and the control(76.9％ and 11.4％ respectively,X2=31.9,P＜0.01).② The frequencies of Th17 cells,Th17/Treg ratio,Th17 cells associated cytokines as IL-6,IL-17a,IL-23,TNF-α,and the Treg cells associated cytokines TGF-31,the serum and synovial fluid anti-CCP antibodies in the RA patients with synovial CCP positive expression were significantly higher in RA patients with CCP positive than those with CCP negative.Disease activity score DAS28 index and histological features quantified variations of the synovial biopsy specimens (synoviocyte hyperplasia,focal aggregates of lymphocytes,and diffuse infiltrat(e)s of lymphocytes) in RA were higher in synovial CCP positive expression patients than in the negative.Conclusion Synovial CCP expression is strongly associated with the Th17/Treg imbalance and synovitis,which may play a crucial role in the pathogenesis of RA.