Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Abstract

Neuromyelitis optica (NMO) and Multiple sclerosis (MS) are two typical inflammatory demyelinating diseases of the central nervous system (CNS) with complex pathogenesis, and they share many similarities. Neuromyelitis optica was considered an optic-spinal form of MS until specific antibodies (NMO-IgG) were suggested to be a biomarker of NMO, distinguishing it from conventional MS 1 . T cells have emerged as a key player in the pathogenesis of MS 2 . We also found increased levels of CD4 + T cells in NMO patients 3 . Simultaneously, B cells are believed to play an important role in the pathogenesis of these diseases. A role of B cells in MS pathogenesis has been suggested by the presence of oligoclonal immunoglobulin bands (OCBs) in cerebrospinal fluid (CSF) 4,5 . In addition, NMO-IgG is compelling evidence for B cells involvement in NMO pathogenesis 6 . Moreover, therapies which eliminate antibodies ABSTRACT: Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. Il-21/Il-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum Il-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) Il-21 in MS and NMO patients still remain unknown. Object: To detect the CSF concentration of Il-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. Methods: CSF Il-21 was detected by an enzyme-linked immunosorbent assay (elISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). Results: CSF concentration of the Il-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between Il-21 and complement in NMO cohort (p=0.023) and high Il-21 levels in autoantibodypositive subgroup (p=0.027). Conclusions: The concentration of CSF Il-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO. RÉSUMÉ: Les niveaux d'IL-21 du liquide céphalo-rachidien dans

IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis

“…The role of IL-21 during neuroinflammatory diseases is relatively unexplored. In multiple sclerosis (MS) and neuromyelitis optica elevated cerebrospinal fluid IL-21 levels and polymorphisms in the IL-21R gene implicate IL-21 in autoimmune pathogenesis (Nohra et al, 2010;Wu et al, 2012). In white matter MS lesions IL-21 expression is primarily restricted to CD4 T cells, while IL-21R is predominantly detected on T and B lymphocytes, and sparsely on cortical neurons (Tzartos et al, 2011).…”

Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase

“…Th17 cells have also been implicated in NMO pathogenesis . High IL‐17, IL‐21, IL‐6, IL‐22 and IL‐8 levels were detected in the serum and CSF from NMO patients during clinical relapse , and these levels were correlated positively with the extent of spinal cord lesions. The production of IL‐6 and IL‐21 by CD4 + T cells at baseline was significantly higher among NMO patients who experienced clinical relapses during follow‐up.…”

“…In humans, the IL-23/IL-1b/IL-6 axis is pivotal in favouring pathogenic Th17 differentiation in autoimmune conditions such as MS [24]. Th17 cells have also been implicated in NMO pathogenesis [10][11][12][13][14][15]. High IL-17, IL-21, IL-6, IL-22 and IL-8 levels were detected in the serum and CSF from NMO patients during clinical relapse [10][11][12][13][14], and these levels were correlated positively with the extent of spinal cord lesions.…”

“…The role of endogenous IL-6 on Th17-related cytokine production by CD4 1 T cells from NMO patients Some studies have implicated Th17-related cytokines in the NMO pathogenesis [10][11][12][13][14][15]. A previous study published by our group [15] demonstrated a direct relationship between IL-21 and IL-6 production by CD4 1 T cells from NMO patients in remission phase with neurological disabilities, determined through EDSS score.…”

“…With regard to the T cell phenotype, some studies have indicated the involvement of T helper type 17 (Th17) cells in the development of demyelinating lesions [10][11][12][13][14][15]. High levels of interleukin (IL)-17, IL-21, IL-6, IL-22 and IL-8 were detected in the serum and in the CSF of NMO patients during clinical relapses [10,11,13,14], and those were correlated positively with the extent of spinal cord lesion [10][11][12][13][14]. High IL-8 levels may explain the increased neutrophil presence in the CSF of these patients [7,11,16].…”