Expression And Significance Of IL-17in CD4~+T Cells Of Active Patients With Systemic Lupus Erythematosus

Objective: Systemic lupus erythematosus(SLE) is a kind of diffuse,systemic autoimmune disease, usually with skin and mucous membrane,musculoskeletal system, the digestive system, the blood system, centralnervous system and the lung, heart, kidney, pancreas and other organsinvolved. Various Antibodies and immunity abnormalities can be detected inserum. The clinical presentation of SLE is very complex, with long course andtending to recrudesce.This disease seriously influences the patient's life qualityand survival rate, especially for women of reproduc-tive age. With adrenalcortical hormone and immunosuppressant in clinical use, the quality of lifeand survival rate of the SLE patients has been improved significantly.However the treatments we have for SLE today have their own adversereactions or abuses, what seriously impact on the treatment of patients withcompliance and prognosis. Patients with SLE cry out for a specific immunetherapy. The etiology and pathogenesis of SLE is still not fully understood, butthe rapid development of modern molecular immunology opens up newpathways to the pathogenesis of SLE.Currently most researchers think that one of the main pathogenesis ofsystemic lupus erythematosus is the destruction of immune tolerance. T cellsplay an important role in establish and maintain of immune tolerance, and thedysfunction of T cells may be an important mechanism of lupus patients. Butit is not very clear. Induced by different cytokines, the original CD4~+T cellsexpress different transcription factors, and differentiate into four subsets withdifferent phenotype and function: Thl, Th2, Treg (regulatory T cells) and Th17.Traditional theory holds that the imbalance of cytokines, produced by Th1/Th2,plays an mainly important role in the pathogenesis of SLE. Whereas researchto Thl and Th2cell does not bring new breakthrough to the pathogenesis of SLE, and at the same time the found of Th17cells poses some new challengesto traditional theory. Domestic and overseas research now focus on Treg andThl7cells newly discovered especially the latter. Thl7cells have clearlydifferent characteristics, independent differentiation and develop-mentprocess, and participate in inflammation process mainly through the secretionof many kinds of effect factors including interleukin-17(IL-17) and so on. Thissubtype plays an important role in mediating chronic inflammation, hostdefense and autoimmune diseases and tumor disease, and turn into a centralpart of the immune response research.Studies show that Th17cells raise the expression of transcriptinregulators, RORγt, through the STAT3signalling pathways, thus code andexpress IL-17and bring the biological effect. Nevertheless Thl7cells in thepathogenic mechanism of SLE is not clear. IL-17is the symbol cytokine andmain effect factor of the Th17cell. Most researches hold that IL-17hasimportant clinical significance for the occurrence and development process inautoimmune diseases,for example, SLE, and shows correlation with diseaseactivity index; But part of the researches do not support the role of IL-17inlupus. In this study, we discuss the role of Th17cells through observating andspeculating the biological function of IL-17in patients with SLE, expect forthe further understanding to the pathogenesis of systemic lupus erythematosusand providing theoretical basis for specific immunology treatment.Methods:76cases were included and divided into three groups:34patients with Systemic lupus erythematosus (group A), all was in active stageand the diagnosis of SLE was established according to the1997revisedcriteria of American College Rheumatology;26patients with other connectivetissue disease(group B), rheumatoid arthritis, systemic scleroderma,dermatomyositis, polymyositis, Sjoegren syndrome, systemic vasculitis wereincluded. All in line with their respective international diagnostic standard; and16cases of Age and sex-matched healthy volunteers as normal controls (groupC). Peripheral venous blood from all studied subjects was collected into tubewith anticoagulant. The proportion of CD4~+IL-17~+T cells in peripheral blood was determined by flow cytometry. Meanwhile the clinical manifestationsincluding the level of ESR, CRP, complement C3, IgG, anti-double-strandsDNA antibody(anti-dsDNA), anti nuclear antibody(ANA) and viscerainvolved and Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score were recorded. The data were analyzed by Statistical Package for SocialSciences software version19.0(SPSS19.0), including comparing theproportions of the CD4~+IL-17~+T cells between groups, analysing thecorrelation between SLEDAI score and the proportion of CD4+IL-17+T cellsin active SLE patients, and the correlation between the proportion ofCD4~+IL-17~+T cells and clinical data.Results:1The proportion of CD4~+IL-17~+T cells in peripheral blood Comparedwith normal control subjects, the proportions of CD4~+IL-17~+T cells inperipheral blood from SLE patients and the other connective tissue diseasepatients were significantly higher(P <0.05). And no significant difference wasfound between SLE and the other connective tissue disease patients (P>0.05).2The correlation between the proportion of CD4+IL-17+T cells andSLEDAI The proportions of CD4~+IL-17~+T cells in active SLE patients werepositively correlated with SLEDAI scores(r=0.353, P=0.047). But there wasno statistical difference between the two groups: low and moderate activitygroup and severe activity group(P <0.05).3The relation between the proportion of CD4~+IL-17~+T cells and clinicalindicator The proportions of CD4~+IL-17~+T cells of SLE patients witharthritis or myositis were higher than those without(P <0.05), and Nosignificant association was found between the proportion of CD4~+IL-17~+Tcells and other indicators, including renal lesion, central nervous systeminvolvement, serositis, mucosal ulcer, fever, new rash and the titer of ANAand anti-dsDNA (P>0.05).4The correlation between the proportion of CD4+IL-17+T cells andlaboratory indicator The proportions of CD4~+IL-17~+T cells were positivelycorrelated with the levels of PLT and β2MG (r=0.543, P <0.001; r=0.406, P=0.017), and it was higher in patients with thrombocytosis than normalWBC counts group (P <0.01). No significant correlation was found betweenthe proportion of CD4+IL-17+T cells and IgG, complement C3, ESR, CRP,WBC, NE%, LY%and HGB (P>0.05), but it was lower in patients withleukocytopenia (P <0.01).Conclusions:1The propotion of CD4~+IL-17~+T cells from patients with Systemic lupuserythematosus or other connective tissue disease increases, which mightsuggest that IL-17participates in the process of various autoimmune diseasesincluding systemic lupus erythematosus, and Th17cells play an important rolein the pathogenesis of SLE.2The propotion of CD4~+IL-17~+T cells,expressed in the peripheral bloodof SLE patients, was positively correlated with SLEDAI score, so that itreflects the disease activity in a certain extent.3Expression level of IL-17shows positive correlation with β2MG, animmunological indictor commonly accepted reflecting the level of humoralimmunity. Th17cells are supposed to stimulate humoral immune response.In conclusion, the study of Th17cell helps to improve the pathogenesisof SLE, and provides the basis for the new target for specific intervention, andmay help to find new pathways on specific immune intervention treatment.