Effect Of IL-33 And The Receptor ST2 On Guillain-barre Syndrome

Guillain-Barré syndrome(GBS)is an immune-mediated inflammatory disease of the peripheral nervous system(PNS),Among the clinical subtypes of acute peripheral neuropathy,the most common subtype is AIDP(acute inflammatory demyelinating polyradiculoneuropathy);another is AMAN(acute motor axonal neuropathy).In addition,the etiology,immunopathogenesis and clinical features between the two subtypes vary considerably among different subtypes.Though the pathogenesis of GBS remains still enigmatic,it is usually accepted as an organ-specific immune-mediated disorder originated by a synergistic interaction between cellular and humoral immune responses to incompletely characterized antigens in the PNS.Previous researches showed that GBS and the animal model experimental autoimmune neuritis(EAN)had been ascribed to Th1 cells-mediated disorders.Recently,series researches have demonstrated that Th17,TH22 and its cytokines also paticipate in the inflammation of GBS in addition to Th1.Numerous chemokines and inflammatory cytokines are thought to play vital roles in initiating,enhancing and perpetuating pathphysiological procedure in GBS.Recently,IL-33 was recognized as a novel IL-1 family member.ST2(homolog of sulfotransferase)receptor is the receptor of IL-33,which is expressed on virouse cell types and participates the inflammatory process,mainly by modulating Th2 response.It participates in immunoregulation and inflammation.It participate in the inflammatory process of Th2 cells involved,adjust the Th2 cytokines activation by the signal pathway mediates the biological activities.Recent studies testified that IL-33 plays important role in the pathogenesis of various autoimmune diseases.But is still not clear whether IL-33 might be implicated in the pathogenesis of GBS and its main subtypes AIDP and AMAN.Objective:In the present study,we detected the levels of IL-33 and ST2 in plasma and CSF of GBS patients at the T1 or T2 phase,and compared with that in ONIDs(n=50),VE/VM(n=20)and health control(n=20).In addition,we assayed the correlations between the two cytokines and GBS functional disability scales(GDSs)as well as a varity of clinical parameters.The studies will help us to understand the role of IL-33 in the development of the autoimmune response in GBS.Methods:34 patients were recruited which fulfilled international diagnostic criteria for GBS,50 other neurological inflammatory disease controls(ONIDs),including 7 MS,34 MG,9 MNDrespectively,20 encephalitis or meningitis infected by virus(VE/VM)and 20 healthy controls(HC)from the Department of Neurology,the First Hospital of Jilin University and Qingdao Medical College During March 2010 to July 2011.All GBS patients were classified neurophysiologically as AIDP(n=21)and AMAN(n=13),using Hadden RD's motor nerve conduction criteria.The blood sample was sampled two times to observe the different course,at acute phase(1-14 days from onset day or T1)and plateau phase(15-32 days from onset day or T2)of GBS.Parts of patients were treated i.v.with IVIg at a dose of 0.4 g/kg body weight per day for 5 days at acute phase consecutively.Severity of GBS was recorded by the method of Hughes degree(a functional disability scale).The plasma and CSF samples were collected and freezed at-80?.ELISA method was used to detect the level of IL-33 and ST2 in line wtih the manufacturer's instructions.All analyses were done in duplicate.The description of the measurement variables were showed as the mean ± SD.About to statistical analysis,differences of mean values were tested with the student-t test for two groups.Reported P-values are two-tailed.Spearman rank test was used for correlation analysis.P<0.05 for the difference was statistically significant.All statistical analyses were performed using SPSS 17.0 software.Results:The sex,age of the subjects in each group was matched,and there was no statistical significance.The IL-33 level in plasma at T1 phase was significantly higher than that of health control(P=0.008),and significantly lower than that in VE/VM control(P=0.0004).The ST2 level in plasma at T1 phase was significantly lower than that in VE/VM control(P<0.00001),however,when compared with health control,there was no statistical significance(P=0.751).The ST2 level in CSF at T1 phase was significantly elevated than that in health control(P<0.001),and significantly lower than that in VE/VM control(P<0.001),however,the IL-33 level in CSF at T1 phase was no statistical significance when compared to either health control or VE/VM control(P>0.05).When compared with T1 phase,the ST2 level in CSF at T2 phase was markedly lower.Though IL-33 and ST2 levels in plasma and IL-33 level in CSF was lower at T2 phase as compared with T1 phase,there was no statistical significance when compared with health control,the IL-33 level in plasma and ST2 level in CSF were still higher at T2 phase(P=0.018,P=0.008),while at T2 phase,ST2 level in CSF in AMAN group was markedly higher than that in AIDP group(P<0.01).At T1 phase,the significant positive relationships were found between the level of IL-33 in plasma and that in CSF(P =0.019,r=0.318),as well as the level of ST2 in plasma and that in CSF(P<0.001,r=0.608).Moreover,there was a positive relationship between the IL-33 level in plasma and Hughes degree both at T1(P =0.012,r=0.433)and T2(P =0.003,r=0.496)phase,as well as ST2 level in CSF and Hughes degree at T1 phase(P =0.042,r=0.550).The significant positive relationships were also found between IL-33 level in plasma and patients treated with IVIg at T2 phase(P<0.001).Conclusion:1.The level of IL-33 and its receptor ST2 in plasma and ncurolymph were increased significantly in GBS patients,as compared with that in the health control group,indicating that increasing circulating IL-33 or ST2 may be involved in the pathogenesis of GBS.2.The level of ST2 in ncurolymph at the T2 phase of GBS was sharply decreased,when compared with that at T1 phase,suggesting that detecting the ST2 level in ncurolymph might help to judging prognosis.