Elevated Serum and Cerebrospinal Fluid CD138 in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Background CD138 (also known as syndecan-1) is an important component of endothelial cell glycocalyx, and it is reportedly involved in negative regulation of various inflammatory processes. The clinical implications of circulating and cerebrospinal fluid (CSF) soluble CD138 (sCD138) in patients with Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis remain unclear. Objective The aim of the current study was to investigate associations between serum and CSF sCD138 levels in anti-NMDAR encephalitis patients. Methods The participants enrolled in the study included 27 with anti-NMDAR encephalitis, 11 with viral meningoencephalitis, and 22 controls. At acute stage and 3 to 6-month follow-up time-points, sCD138, tumor necrosis factor-α, matrix metalloproteinase-2, and matrix metalloproteinase-9 in serum and CSF were measured in all participants via enzyme-linked immunosorbent assays. Results Serum and CSF levels of sCD138 were significantly increased in patients with anti-NMDAR encephalitis. Furthermore, after 3–6 months of follow-up CSF sCD138 levels were significantly decreased in anti-NMDAR encephalitis patients. Changes in sCD138 levels were significantly associated with amelioration of modified Rankin Scale scores in patients with anti-NMDAR encephalitis. Conclusion In anti-NMDAR encephalitis patients, high circulating, and CSF sCD138 is associated with inflammation and poor clinical prognosis. The present study suggests that sCD138 may be an informative biomarker of inflammation in anti-NMDAR encephalitis.

[1]  Yu Peng,et al.  Cell-Free Mitochondrial DNA in the CSF: A Potential Prognostic Biomarker of Anti-NMDAR Encephalitis , 2019, Front. Immunol..

[2]  F. Zimprich,et al.  Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients , 2018, Front. Immunol..

[3]  H. Tomita,et al.  Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier , 2018, Scientific Reports.

[4]  S. Pan,et al.  Elevated soluble syndecan‐1 levels in neuromyelitis optica are associated with disease severity , 2018, Cytokine.

[5]  S. Pan,et al.  Elevated Soluble Fas and FasL in Cerebrospinal Fluid and Serum of Patients With Anti-N-methyl-D-aspartate Receptor Encephalitis , 2018, Front. Neurol..

[6]  S. Pan,et al.  Elevation of YKL-40 in the CSF of Anti-NMDAR Encephalitis Patients Is Associated With Poor Prognosis , 2018, Front. Neurol..

[7]  D. Fatovich,et al.  Glycocalyx biomarker syndecan‐1 is a stronger predictor of respiratory failure in patients with sepsis due to pneumonia, compared to endocan , 2018, Journal of critical care.

[8]  H. Flyvbjerg,et al.  Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood–brain barrier , 2018, Proceedings of the National Academy of Sciences.

[9]  J. Rungby,et al.  Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers? , 2018, Front. Immunol..

[10]  M. Kersten,et al.  Syndecan-1 promotes Wnt/β-catenin signaling in multiple myeloma by presenting Wnts and R-spondins. , 2018, Blood.

[11]  A. Goetz,et al.  Syndecan-1 as a biomarker for sepsis survival after major abdominal surgery. , 2018, Biomarkers in medicine.

[12]  S. Pan,et al.  Glycocalyx degradation leads to blood–brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  H. Ehrenreich.  Autoantibodies against the N-Methyl-d-Aspartate Receptor Subunit NR1: Untangling Apparent Inconsistencies for Clinical Practice , 2017, Front. Immunol..

[14]  K. Chu,et al.  Distinct intrathecal interleukin-17/interleukin-6 activation in anti-N-methyl-d-aspartate receptor encephalitis , 2016, Journal of Neuroimmunology.

[15]  A. Venkatesan,et al.  A clinical approach to diagnosis of autoimmune encephalitis , 2016, The Lancet Neurology.

[16]  A. Fox-Robichaud,et al.  Syndecan-1 (CD138) deficiency increases Staphylococcus aureus infection but has no effect on pathology in a mouse model of peritoneal dialysis , 2016, Journal of Biomedical Science.

[17]  A. Goy,et al.  Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine , 2015, Oncotarget.

[18]  Ji-Young Kim,et al.  Elevated Serum Levels of Syndecan-1 Are Associated with Renal Involvement in Patients with Systemic Lupus Erythematosus , 2015, The Journal of Rheumatology.

[19]  N. Nordsborg,et al.  Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans , 2014, Front. Physiol..

[20]  Peter L. Voyvodic,et al.  Loss of Syndecan-1 Induces a Pro-inflammatory Phenotype in Endothelial Cells with a Dysregulated Response to Atheroprotective Flow* , 2014, The Journal of Biological Chemistry.

[21]  Chuan Wu,et al.  EncephalomyelitisPlexus in Murine Experimental Autoimmune Recruitment to the Brain across the Choroid Negatively Regulates Initial Leukocyte Syndecan-1, a Cell Surface Proteoglycan, , 2013 .

[22]  M. Koopman,et al.  Damage of the endothelial glycocalyx in dialysis patients. , 2012, Journal of the American Society of Nephrology : JASN.

[23]  M. Fritzler,et al.  Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology. , 2012, Autoimmunity reviews.

[24]  S. Grundmann,et al.  Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome. , 2012, Resuscitation.

[25]  J. Horváth,et al.  Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis , 2011, Neurology.

[26]  L. Rasmussen,et al.  A High Admission Syndecan-1 Level, A Marker of Endothelial Glycocalyx Degradation, Is Associated With Inflammation, Protein C Depletion, Fibrinolysis, and Increased Mortality in Trauma Patients , 2011, Annals of surgery.

[27]  K. Peter,et al.  Shedding of the Endothelial Glycocalyx in Patients Undergoing Major Vascular Surgery With Global and Regional Ischemia , 2007, Circulation.

[28]  Dick W. Slaaf,et al.  The endothelial glycocalyx: composition, functions, and visualization , 2007, Pflügers Archiv - European Journal of Physiology.

[29]  H. Bangstad,et al.  Increased syndecan-1 in serum is related to early nephropathy in type 1 diabetes mellitus patients , 2006, Diabetologia.

[30]  G. Pinkus,et al.  CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. , 2004, American journal of clinical pathology.

[31]  M. Remberger,et al.  Increased levels of syndecan-1 in serum during acute graft-versus-host disease. , 2003, Transplantation.

[32]  Dianjun Cao,et al.  High levels of soluble syndecan-1 in myeloma-derived bone marrow : modulation of hepatocyte growth factor activity , 2000 .

[33]  D. Hilfiker-Kleiner,et al.  Regulation and function of endothelial glycocalyx layer in vascular diseases. , 2018, Vascular pharmacology.