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The Role Of IL-23in The Pathogenesis Of Systemic Lupus Erythematosus

Posted on:2016-01-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:J DuFull Text:PDF
GTID:1224330467495457Subject:Internal Medicine
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Systemic lupus erythematosus (SLE) is an autoimmune disease thatcan affect essentially any organ or tissue, which results in severe damageparticularly afecting the joints, skin, brain and kidneys.One of its mostsevere manifestations is lupus nephritis (LN), which remains a cause ofsubstantial morbidity.The incidence and prevalence of LN overallgenerally range from50%to100%and Lupus nephritis is a seriouspotential feature and patients often eventually succumb to end-stagekidney. Both innate an dadaptive immune are involved in the SLE and LN,but the precise pathophysiologic mechanisms that underlie thedevelopment of SLE and LN is still unclear, especially the relativeimportance of the cytokines operative in these systems is drawinggrowing attention.Accumulating evidence indicates that Th17cells andIL-17play animportant role in the pathogenesis of SLE.Elevated IL-17levels have been detected in sera,and enhanced expression of IL-17hasbeen observedin target tissues of SLE patients. But the development,expansion, and proliferation of Th17cells and production of IL-17areregulated by cytokines including IL-23, IL-6, and IL-21.Thedifferentiation of naive CD4+T cells into Th17cells and effector T cellsis regulated and initiated by IL-23. A recent publication has reportedIL-23deficient mice are resistant to experimental autoimmuneencephalomyelitis and collagen induced arthritis disease development andelevation of IL-23p19in human autoimmune disease such as multiple sclerosis.In addition, IL-23/IL-17also takes part in the development ofSLE.these findings suggest that abnormally active IL-23may contributeto thepathogenesis of SLE.The present study aimed to examine the role ofIL-23levels SLE of Chinese Han patients.Our results provide the basisfor a comprehensive study of the role of IL-23in SLE and LN.The study consists of six sections as follows:1. To evaluate clinical parameters of SLE patients and healthycontrols.This study is divided into three groups; patients with SLE according to therenal involvement were divided into LN group, non LN group, and healthcontrol group respectively. Patients who were suffering from serious diseaseswere excluded from the study. Control subjects were recruited from amongindividuals who had not been diagnosed with SLE and were seeking a routinehealth check-up at the Physical Health Examination Centre of Jilin ProvincialPeople’s Hospital. Of the patients with SLE,128(81.0%) werefemale.Nephritis was observed in50.0%(79/158) of patients. the joints, skin,brain, kidneys and so forth are affected.2. The characteristics of serum IL-23mRNA levels of SLE patientsThe result of RT-PCR shows that serum IL-23mRNA levels are significantlyhigher in the158SLE patients (66.42±8.35) compared with the60healthycontrols (37.05±4.67). There are no significant diferences in serum IL-23mRNA concentrations among male SLE patients (65.71±8.79) andfemale SLE patients (67.06±8.24) and no significant diference isobserved between patients with inactive (65.95±6.12) SLE or active SLE(67.19±6.24).3. The characteristics of serum the radio of IL-17mRNA/IL-23mRNA SLE patients The result of RT-PCR shows that the ratio of IL-17mRNA/IL-23mRNAis significantly higher in patients with active SLE (73.30±3.00) comparedwith those with inactive disease (66.66±2.35) and healthy control subjects(37.40±4.68).A strong positive correlation between serum IL-23mRNA and IL-17mRNA levels was determined at study entry (r=0.2658,P<0.05).Theresults suggest that IL-17and IL-23take part in the development of SLE.4. The relationship of serum IL-23mRNA levels of SLE patientsand lupus nephritis (LN)This study is divided into two groups; patients with SLE accordingto the renal involvement were divided into LN group and non LN grouprespectively.Serum IL-23mRNA concentrations were significantlyincreased in patients determined to have LN (70.55±5.00) compared withpatients non LN (55.67±5.01) or healthy control subjects(36.88±4.54).These data suggests that IL-23mRNA play a crucial role inSLE and renal involvement.5. The relationship of serum IL-23mRNA levels and Renal SLEDAIscoreA strong positive correlation between serum IL-23mRNA level andSLEDAI score in SLE patients with LN was determined at study entry(r=0.9210,P<0.0001). The results suggest that IL-23had the largestcorrelation with SLEDAI score in SLE patients with LN.6. The characteristics of protein expression of the IL-17and IL-23ofLN patients.Serum IL-23is significantly increased in patients determined to haveLN (581.2±166.80pg/mL) compared with SLE patients withoutLN(345.3±91.21pg/mL) or healthy control subjects (195.3±53.96pg/mL),Serum IL-23is significantly increased in patients determined to have LN (581.2±166.80pg/mL) compared with SLE patients withoutLN(345.3±91.21pg/mL).These data suggests that IL-23play a crucialrole in LN.Serum IL-17is significantly increased in patients determined to haveLN (28.17±8.16pg/mL) compared with SLE patients without LN(29.31±8.15pg/mL) or healthy control subjects (4.86±1.34pg/mL).butthere have not significant differencet of LN patients and SLE patientswithout LN.We firstly investigated that IL-23mRNA level is increased in SLEpatients;There were no significant diferences in serum IL-23mRNAconcentrations among SLE patients according to age or sex, and nosignificant diference was observed between patients with inactive oractive SLE. In addition, we find that there have close relationshipbetween patients with inactive or active SLE. Previous publicationreported that the protein expression of IL-23is increased in active SLEpatients. Furthermore, our results suggest that the IL-23have closerelationship with development of LN and the protein expression of IL-23is in association with the LN. These findings suggest that IL-23may playan important role in SLE pathogenesis, and that the IL-17/IL-23ratio maybe useful biomarker foractive disease, and that the IL-23play a crucialrole in SLE and renal involvement.In word, this study could contribute toa better understanding of the Pathogenesis of SLE and provide the newtarget for theraping SLE and LN.
Keywords/Search Tags:Systemic lupus erythematosus, lupus nephritis, IL-23, IL-17/IL-23
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