Anti-N-methyl-D-aspartate receptor encephalitis: the clinical course in light of the chemokine and cytokine levels in cerebrospinal fluid
Open Access
- 3 March 2016
- journal article
- case report
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 13 (1), 55
- https://doi.org/10.1186/s12974-016-0507-9
Abstract
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1–26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls. Modified Rankin score (mRS) defined the clinical status. The concentrations of the chemokines (C-X-C motif ligand (CXCL)10, CXCL8 and C-C motif ligand 2 (CCL2)) and the cytokines (interferon (IFN)γ, interleukin (IL)4, IL7, IL15, IL17A and tumour necrosis factor (TNF)α) were measured with Luminex multiple bead technology. The B cell-activating factor (BAFF) and CXCL13 concentrations were determined via enzyme-linked immunosorbent assay. We correlated the disease period with the mRS, pleocytosis and the levels of all of the investigated chemokines and cytokines. Non-parametric tests were used, a P value <0.05 was considered to be significant. The increased CXCL10 and CXCL13 CSF levels accompanied early-stage disease progression and pleocytosis. The CSF CXCL10 and CXCL13 levels were the highest in the most complicated patient. The CSF BAFF levels remained unchanged through the periods. In contrast, the CSF levels of T cell-related cytokines (INFγ, TNFα and IL17A) and IL15 were slightly increased at all of the periods examined. No dynamic changes in chemokine and cytokine levels were observed in the peripheral blood. Our data support the hypothesis that anti-NMDAR encephalitis is restricted to the CNS and that chemoattraction of immune cells dominates at its early stage. Furthermore, our findings raise the question of whether T cells are involved in this disease. The online version of this article (doi:10.1186/s12974-016-0507-9) contains supplementary material, which is available to authorized users.Keywords
This publication has 26 references indexed in Scilit:
- Essentials of Th17 cell commitment and plasticityBlood, 2013
- Astrocyte-Derived CXCL10 Drives Accumulation of Antibody-Secreting Cells in the Central Nervous System during Viral EncephalomyelitisJournal of Virology, 2013
- BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapyJournal of Neuroinflammation, 2013
- Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort studyThe Lancet Neurology, 2013
- B cells and antibodies in multiple sclerosis pathogenesis and therapyNature Reviews Neurology, 2012
- Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiologyAutoimmunity Reviews, 2012
- IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasisSeminars in Immunology, 2012
- CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammationJournal of Neuroinflammation, 2012
- Flow cytometric characterization of cerebrospinal fluid cellsCytometry Part B: Clinical Cytometry, 2011
- Update on anti-N-methyl-D-aspartate receptor encephalitis in children and adolescentsCurrent Opinion in Pediatrics, 2010