The Possible Impact Of IP-10and Regulatory T Cell With Juvenile Idiopathic Arthritis

PART ONE: THE EXPRESSION AND SIGNIFICANCE OFIL-6、IP-10AND IL-17IN SERUM AND SYNOVIAL FLUIDWITH JUVENILE IDIOPATHIC ARTHRITISObjective To detect the disparity of three cytokines aboutInterleukin-6(IL-6),Interferon-Inducible Protein10(IP-10) and Interleukin-17(IL-17)in peripheral blood(PB) and synovial fluid(SF) of patients withjuvenile idioPathic arthritis (JIA).Method Serum concentrations of the three cytokines were measuredin27patients with13systemic-onset JIA(sJIA)，14polyarticular JIA(pJIA)and28healthy controls using enzyme-linked immunoabsorbent assays(ELISA).19patients being no marked arthritis symptom or only temporaryarthralgia enrolled in probable sJIA group. SF from18patients with7sJIA,11pJIA were examined for cytokine levels.Result1. The statistically difference of serum IL-6was detectedbetween sJIA and health control group[28.01(4.23～59.2) vs.12.25(2.09～13.8),P＜0.05], but no statistically difference between suspected sJIA and health control group[11.84(7.70～39.21) vs.12.25(2.09～13.8),P＞0.05].There were statistically significant differences between sJIA group andhealth control group in serum concentrations of IL-17[13.95(9.8～34.3) vs.9.81(7.88～16.15),P＜0.05], yet compared to health control group, thestatistically difference concentration level of IL-17wasn’t found in pJIAgroup[14.19(9.93～16.94) vs.9.81(7.88～16.15),P＞0.05].2. In sJIA andpJIA SF, The median IP-10level was significantly higher compared torespective PB levels [619.66(160.94,873.07) vs.64.78(27.37～111.94)；660.91(401.92,1349.8) vs.97.4(41.85～222.14),P＜0.01, respectively],butthere was only significant difference in IL-17between pJIA SF andPB[22.94(17.08,45.8) vs.14.19(9.93～16.94),P＜0.01].3. In sJIA serum,there were strongly positive and correlation of IL-6with ESR andDAS28(r=0.787,P＜0.01；r=0.780,P＜0.01); The positive correlation alsoexisted between IL-6and serum IL-17in sJIA group(r=0.758,P＜0.05).4.We also found that IP-10was associated with IL-17in SF(r=0.733,P<0.05),but there was significant negative correlation between IP-10and IL-17inserum(r=-0.802,P<0.01).Conclusion1.IL-6may indicate more important role in thepathogenesis of sJIA. Moreover,IL-6maybe the biomarker associated witharthritis in early JIA stage.2.Both autoinflammation and autoimmuneresponse maybe involved in the pathogenesis of sJIA3.IL-17enrichmentmay only occur in local joint,the levels of IL-17in PB may not be significantly increased.4.The prominent expression gradient between SFand PB of IP-10maybe the basic of performing chemotaxis to Th17cells andfurther causing joint damage. PART TWO: THE EXPRESSION OF IP-10RECEPTOR ONREGULATORY T CELL SURFACE WITH JUVENILEIDIOPATHIC ARTHRITISObjective To analysis the expression disparity of regulatory T cell(Treg) and Interferon-Inducible protein10(IP-10) receptor CXCR3inperipheral blood(PB) and synovial fluid(SF) of patients with juvenileidiopathic arthritis (JIA).Method Paired samples of peripheral blood (PB) and synovialfluid(SF) from7patients with JIA were collected From April2012toFebruary2013. PB was collected from11patients with first diagnosised JIAin our hospital and8healthy controls.Treg and CXCR3+Treg in PB and SFwere characterized using flow cytometry. Chemokines IP-10were measuredusing ELISA.Results1.The concentration of IP-10wasn’t increased significantly in SF compared with paired PB from JIA patients[(619.92±335.95) pg/mlvs.(340.62±180.2) pg/ml,P＞0.05];The frequency of Treg cells wasn’treduced significantly in SF compared with paired PB.2.The concentration ofIP-10in PB from first diagnosised JIA patients was significantly higher thanin PB from healthy controls [(683.15±326.04) pg/ml vs.(252.15±52.45)pg/ml,P＜0.01].The frequency of CXCR3positive Treg cells in PB totalTreg from first JIA patients was significantly higher than in PB from healthycontrols[(35.43±12.53)%vs.(16.58±3.88),P＜0.01].3. Notably,thefrequency of CXCR3positive Treg cells in PB total Treg was30.01%,butonly0.93%in SF.Conclusion The quantity of Treg cells in PB and SF maybe relatedwith the frequency of IP-10receptor CXCR3on Treg cells surface.AndIP-10may influence the balance of Th17and Treg cells.