Guillain-Barré Syndrome(GBS) In Southern China-The Role Of Th17 Pathway In The Pathogenesis Of Demyelinating GBS

Part 1 Guillain-Barre syndrome in southern China,retrospective analysis of hospitalized patientsObjectivesThe axonal Guillain-Barre syndrome(GBS)in northern China has been widely concerned all over the world,but China is a vast country with obvious differences in climate and environment between the north and the south region.The clinical and epidemiological profiles of GBS in southern china have yet to be fully recognized.We aimed to investigate the subtypes of GBS in southern china,compare the clinical features of demyelinating form with that of axonal form and test whether preceding infections and age have influence on the clinical phenotype,disease course and severity of GBS.MethodsMedical records of patients with a diagnosis of GBS admitted to 31 tertiary hospitals,located in 14 provinces in southern china,from 1 January 2013 to 30 september 2016,were collected and retrospectively reviewed.ResultsFinally.1056 patients,including 887 classic GBS and 169 variants,were enrolled.The 661 classic patients with available electromyographic data were grouped as having acute inflammatory demyelinating polyneuropathy(AIDP,49.0%),acute motor axonal neuropathy(AMAN,18.8%),inexcitable(0.9%)and equivocal(31.3%).In contrast to AIDP,patients with AMAN were characterized by earlier nadir(p=0.000),higher hughes score at nadir(p=0.003)and at discharge(p=0.000).preceding upper respiratory infections were identified in 369(34.9%)patients,who were more inclined to develop AIDP(p=0.000)and Miller-Fisher syndrome(p=0.027),whereas gastrointestinal infection were found in 89(8.4%)patients,who were more prone to develop AMAN(p=0.000),with more severe illness(p=0.001)and longer hospital stay(p=0.009).children(<15 years)and the elderly(>56 years)were more severe at nadir,the elderly had the longest hospital stay(p=0.023).ConclusionAIDP is the predominant form in southern china,which is different from data of northern china.The different subtypes,preceding infection and age of onset can partially determine the disease progression,severity and short-term recovery speed of GBS.Part 2 The role of Th17 pathway in the pathogenesis of demyelinating Guillain-Barré syndromeObjectivesHelper T cell 17(Th17),a newly discovered T cell subpopulation,has been implicated in the pathogenesis of autoimmune diseases such as multiple sclerosis and asthma.Several studies has pointed that cytokine 17(IL-17)may be pathogenic in Guillain-Barre syndrome(GBS)/experimental autoimmune neuritis(EAN).However,little is known concerning the IL-17 expression changes trend during the whole course of disease,and the mechanism is unclear.What's more,whether drugs specially targeting Th17 cells or their cytokines have potential effects on demyelinating GBS/EAN is uncertain.MethodsThe EAN model was established,and the expression changes of target genes and proteins in semm and tissues were explored by real-time quantitative polymerase chain reaction,enzyme-linked immunosorbent assay,and western blot assay,in order to further clarify the effecting phase of Th17 cells and their cytokines in the EAN,and to preliminarily uncover the underlying mechanisms.ResultsPart 1:The serum IL-17 and IL-6 levels increased gradually as the disease progressed,the serum IL-17 in the EAN group was significantly higher than that in the control group on day 14 p.i.and day 17 p.i.(p<0.05),as was the serum IL-6 level.As the EAN progressed,the phosphorylation levels of JAK1 and STAT3 of the sciatic nerve increased(p<0.05);the mRNA levels of IL-17,IL-6 and ROR?t in the spleen,lymph nodes and sciatic nerve were up-regulated,while the mRNA levels of FoxP3 were gradually down-regulated(P<0.05).Part 2:The novel RORyt inhibitors,not only delayed the onset of EAN,but also significantly decreased the neurological severity of EAN(p<0.05).The serum levels of IL-17 and RORyt in the RORyt-IN-1-treated group and the control group increased gradually with the progression of the disease,and decreased gradually after the disease peaked.However,the serum levels of IL-17 and RORyt in the RORyt-IN-1-treated group were lower than those in the control group on the day 14 p.i.,day 17 p.i.and day 28 p.i.(p<0.05);Part 3:At the peak time,inflammatory cell infiltration was significantly reduced in the rats treated with RORyt-IN-1.Spleen,lymphonodus and sciatic nerves from RORyt-IN-1-treated rats showed a significantly reduced expression of IL-17 mRNA and RORyt mRNA,compared to those tissues from DMSO-treated group(p<0.05).ConclusionsTh17 cells and their cytokines are closely associated with the onset of EAN and IL-6/JAK1/STAT3 signaling pathway may be the main mechanism of its effect.The novel RORyt inhibitors may be prospective strategies in treating GBS.