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

Abstract

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.

Human glycocalyx shedding: Systematic review and critical appraisal

“…Exceptions are quite rare (Table 1, top). One study on encephalitis showed elevated concentrations of sdc‐1 in the cerebrospinal fluid 62 . By contrast, studies of diabetes more rarely report increased concentrations of glycocalyx degradation products.…”

High Level of Soluble CD146 In Cerebrospinal Fluid Might be a Biomarker of Severity of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

“…In previous studies, abnormal elevation of sCD146 has been reported to correlate with proinflammatory factors, such as TNF-α, IL-13 and IL-17 ( 5 , 27 ). Early research by our team confirmed that the presence of inflammatory factors in the CSF of anti-NMDAR encephalitis patients reflect the activity of the disease ( 8 , 9 , 17 , 28 – 30 ). In the present study, we considered that local inflammation in the brain was activated, leading to the accumulation of inflammatory factors in the CSF that enhanced the expression of sCD146, ultimately promoting BBB dysfunction.…”

“…The soluble form of CD146 (sCD146) comes from shedding of the extracellular portion of CD146 via matrix metalloproteinases (MMPs) ( 5 – 7 ). Studies have proven that MMPs are elevated in anti-NMDAR encephalitis ( 8 , 9 ), and to date, higher sCD146 has been found in chronic obstructive pulmonary disease ( 10 ), active inflammatory bowel disease ( 11 ), systemic sclerosis ( 12 , 13 ), chronic renal disease ( 14 , 15 ) and CNS diseases including multiple sclerosis (MS) ( 16 , 17 ), neuromyelitis optica ( 16 ), CNS infections, peripheral neuropathy and Alzheimer’s disease ( 4 – 6 , 18 , 19 ). BBB integrity and low permeability are necessary for maintaining normal function of the CNS, and BBB disruption may play an important role in anti-NMDAR encephalitis ( 16 , 18 , 20 ).…”

High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica

“…To date, most studies that have assayed glycocalyx have focused on vascular diseases and cancer. Some studies, however, have linked glycocalyx components with encephalitis in NMO, experimental autoimmune encephalomyelitis, and anti-NMDA receptor encephalitis (21)(22)(23), although a holistic understanding of glycocalyx degradation in IIDDs is lacking.…”