Clinical study| Volume 75, P176-180, May 2020

Download started.


Evidence of altered Th17 pathway signatures in the cerebrospinal fluid of patients with Guillain Barré Syndrome

Published:March 23, 2020DOI:


      • Cytokines mediate the progression and recovery of GBS.
      • CSF cytokines of Th17 pathway are associated with GBS.
      • CSF cytokines of Th17 pathway influence symptom duration in GBS.


      Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barré Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Neuroscience
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ang C.W.
        • Jacobs B.C.
        • Laman J.D.
        The Guillain-Barre syndrome: a true case of molecular mimicry.
        Trends Immunol. 2004; 25: 61-66
        • Wanschitz J.
        • Maier H.
        • Lassmann H.
        • Budka H.
        • Berger T.
        Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barre syndrome.
        Brain. 2003; 126: 2034-2042
        • Han R.K.
        • Cheng Y.F.
        • Zhou S.S.
        • Guo H.
        • He R.D.
        • Chi L.J.
        • et al.
        Increased circulating Th17 cell populations and elevated CSF osteopontin and IL-17 concentrations in patients with Guillain-Barre syndrome.
        J Clin Immunol. 2014; 34: 94-103
        • Ebrahim Soltani Z.
        • Rahmani F.
        • Rezaei N.
        Autoimmunity and cytokines in Guillain-Barre syndrome revisited: review of pathomechanisms with an eye on therapeutic options.
        Eur Cytokine Netw. 2019; 30: 1-14
        • Illes Z.
        • Blaabjerg M.
        Cerebrospinal fluid findings in Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathies.
        Handb Clin Neurol. 2017; 146: 125-138
        • Ziganshin R.H.
        • Ivanova O.M.
        • Lomakin Y.A.
        • Belogurov Jr., A.A.
        • Kovalchuk S.I.
        • Azarkin I.V.
        • et al.
        The pathogenesis of the demyelinating form of Guillain-Barre syndrome (GBS): proteo-peptidomic and immunological profiling of physiological fluids.
        Mol Cell Proteom. 2016; 15: 2366-2378
        • Gonzalez-Quevedo A.
        • Carriera R.F.
        • O'Farrill Z.L.
        • Luis I.S.
        • Becquer R.M.
        • Luis Gonzalez R.S.
        An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain Barre syndrome.
        Neurology. 2009; 57: 288-294
        • Wang X.K.
        • Zhang H.L.
        • Meng F.H.
        • Chang M.
        • Wang Y.Z.
        • Jin T.
        • et al.
        Elevated levels of S100B, tau and pNFH in cerebrospinal fluid are correlated with subtypes of Guillain-Barre syndrome.
        Neurological Sci. 2013; 34: 655-661
        • Li C.
        • Zhao P.
        • Sun X.
        • Che Y.
        • Jiang Y.
        Elevated levels of cerebrospinal fluid and plasma interleukin-37 in patients with Guillain-Barre syndrome.
        Mediators Inflamm. 2013; 2013639712
        • Debnath M.
        • Nagappa M.
        • Subbanna M.
        • Sundaravadivel P.
        • Talukdar P.M.
        • Shivakumar V.
        • et al.
        Th17 pathway signatures in a large Indian cohort of Guillain Barre syndrome.
        J Neuroimmunol. 2018; 323: 125-130
        • Li S.
        • Jin T.
        • Zhang H.L.
        • Yu H.
        • Meng F.
        • Concha Quezada H.
        • et al.
        Circulating Th17, Th22, and Th1 cells are elevated in the Guillain-Barre syndrome and downregulated by IVIg treatments.
        Mediators Inflamm. 2014; 2014740947
        • Li S.
        • Yu M.
        • Li H.
        • Zhang H.
        • Jiang Y.
        IL-17 and IL-22 in cerebrospinal fluid and plasma are elevated in Guillain-Barre syndrome.
        Mediators Inflamm. 2012; 2012260473
        • Asbury A.K.
        • Cornblath D.R.
        Assessment of current diagnostic criteria for Guillain-Barre syndrome.
        Ann Neurol. 1990; 27: S21-S24
        • Merkies I.S.
        • Schmitz P.I.
        • van der Meche F.G.
        • Samijn J.P.
        • van Doorn P.A.
        Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies.
        J Neurol Neurosurg Psychiatry. 2002; 72: 596-601
        • Hadden R.D.
        • Cornblath D.R.
        • Hughes R.A.
        • Zielasek J.
        • Hartung H.P.
        • Toyka K.V.
        • et al.
        Electrophysiological classification of Guillain-Barre syndrome: clinical associations and outcome. Plasma exchange/Sandoglobulin Guillain-Barre Syndrome Trial Group.
        Ann Neurol. 1998; 44: 780-788
        • Rajabally Y.A.
        • Durand M.C.
        • Mitchell J.
        • Orlikowski D.
        • Nicolas G.
        Electrophysiological diagnosis of Guillain-Barre syndrome subtype: could a single study suffice?.
        J Neurol Neurosurg Psychiatry. 2015; 86: 115-119
        • Weller R.O.
        Pathology of cerebrospinal fluid and interstitial fluid of the CNS: significance for Alzheimer disease, prion disorders and multiple sclerosis.
        J Neuropathol Exp Neurol. 1998; 57: 885-894
        • Weller R.O.
        How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and Alzheimer’s diseases?.
        J Pathol. 2001; 194: 1-3
        • Press R.
        • Pashenkov M.
        • Jin J.P.
        • Link H.
        Aberrated levels of cerebrospinal fluid chemokines in Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.
        J Clin Immunol. 2003; 23: 259-267
        • Sainaghi P.P.
        • Collimedaglia L.
        • Alciato F.
        • Leone M.A.
        • Naldi P.
        • Molinari R.
        • et al.
        The expression pattern of inflammatory mediators in cerebrospinal fluid differentiates Guillain-Barre syndrome from chronic inflammatory demyelinating polyneuropathy.
        Cytokine. 2010; 51: 138-143
        • Sun T.
        • Chen X.
        • Shi S.
        • Liu Q.
        • Cheng Y.
        Peripheral blood and cerebrospinal fluid cytokine levels in Guillain Barre syndrome: a systematic review and meta-analysis.
        Front Neurosci. 2019; 13: 717
        • Li P.
        • Wang S.
        • Zhang R.
        • Pei J.
        • Chen L.
        • Cao Y.
        • et al.
        Identification of CSF biomarkers by proteomics in Guillain-Barre syndrome.
        Exp Ther Med. 2018; 15: 5177-5182
        • Wang X.
        • Zheng X.Y.
        • Ma C.
        • Wang X.K.
        • Wu J.
        • Adem A.
        • et al.
        Mitigated Tregs and augmented Th17 cells and cytokines are associated with severity of experimental autoimmune neuritis.
        Scand J Immunol. 2014; 80: 180-190
        • Debnath M.
        • Nagappa M.
        • Talukdar P.M.
        • Subbanna M.
        • Sundaravadivel P.
        • Shivakumar V.
        • et al.
        Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barre Syndrome.
        Cytokine. 2018; 110: 58-62
        • Maimone D.
        • Annunziata P.
        • Simone I.L.
        • Livrea P.
        • Guazzi G.C.
        Interleukin-6 levels in the cerebrospinal fluid and serum of patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.
        J Neuroimmunol. 1993; 47: 55-61
        • Korn T.
        • Mitsdoerffer M.
        • Croxford A.L.
        • Awasthi A.
        • Dardalhon V.A.
        • Galileos G.
        • et al.
        IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells.
        PNAS. 2008; 105: 18460-18465
        • Yang X.O.
        • Pappu B.P.
        • Nurieva R.
        • Akimzhanov A.
        • Kang H.S.
        • Chung Y.
        • et al.
        T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma.
        Immunity. 2008; 28: 29-39
        • Mathur A.N.
        • Chang H.C.
        • Zisoulis D.G.
        • Stritesky G.L.
        • Yu Q.
        • O'Malley J.T.
        • et al.
        Stat3 and Stat4 direct development of IL-17-secreting Th cells.
        J Immunol. 2007; 178: 4901-4907
        • Yang X.O.
        • Panopoulos A.D.
        • Nurieva R.
        • Chang S.H.
        • Wang D.
        • Watowich S.S.
        • et al.
        STAT3 regulates cytokine-mediated generation of inflammatory helper T cells.
        J Biol Chem. 2007; 282: 9358-9363
        • Wu X.
        • Wang J.
        • Liu K.
        • Zhu J.
        • Zhang H.L.
        Are Th17 cells and their cytokines a therapeutic target in Guillain-Barre syndrome?.
        Expert Opin Ther Targets. 2016; 20: 209-222