Elevated Soluble Fas and FasL in Cerebrospinal Fluid and Serum of Patients With Anti-N-methyl-D-aspartate Receptor Encephalitis.

Yue-Wen Ding,Hai-Ying Shen,Wei Xie,Su-Yue Pan,Hong-Hao Wang

doi:10.3389/fneur.2018.00904

Yue-Wen Ding, Hai-Ying Shen + Show 3 more

Open Access

https://doi.org/10.3389/fneur.2018.00904

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Abstract

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder that mainly affects children and young women. The Fas system contains both membrane-bound versions of Fas (mFas) and Fas ligand (mFasL), and soluble versions (sFas and sFasL), which play important roles in apoptosis and regulation of the immune system. Both the levels of sFas and sFasL and the role they play in anti-NMDAR disease pathogenesis remain unclear.Methods: Forty-eight pairs of cerebrospinal fluid (CSF) and serum were collected from patients with anti-NMDAR encephalitis, encephalitis of other causes or peripheral neuropathy. The CSF and serum concentrations of sFas and sFasL were determined with enzyme-linked immunosorbent assay.Results: CSF concentrations of sFas and sFasL were both increased in anti-NMDAR encephalitis patients compared with controls patients. Serum sFas levels were also elevated in anti-NMDAR encephalitis patients relative to controls. sFas and sFasL concentrations in CSF positively correlated with the modified Rankin scale (mRS) both at onset and 6-months follow-up.Conclusion: CSF sFas and sFasL levels were elevated in anti-NMDAR encephalitis patients, and reflect the disease severity of anti-NMDAR encephalitis.

Highlights

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a newly recognized immune-mediated disorder that mainly affects children and young women [1]
SFas and sFasL Concentration Are Increased in Anti-NMDAR Encephalitis Patients
Increased cerebrospinal fluid (CSF) sFas level was significant correlated with disease severity (p = 0.0011). Both sFas and sFasL levels in CSF correlated with disease severity at the 6-months follow-up (p = 0.0025 [sFas], p = 0.019 [sFasL]), but serum levels of sFas and sFasL did not correlate with onset modified Rankin scale (mRS) or mRS at 6-months follow-up. In this case–control study, we examined the concentrations of sFas and sFasL in 48 pairs of CSF/serum samples from patients with anti-NMDAR encephalitis [18] and controls [18]

Summary

Introduction

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a newly recognized immune-mediated disorder that mainly affects children and young women [1]. Reports studying the effects of anti-NDMAR antibodies in the cerebrospinal fluid (CSF) of patients suggest an antibody mediated selective and reversible internalization of receptors from the cell surface [5, 6], leading to further pathogenesis [7]. Fas (CD95, apoptosis antigen 1) and Fas ligand (FasL, CD95L or TNFSF6) both belong to the death receptor subfamily of the TNF receptor superfamily [8]. Extrinsic apoptosis pathway would be triggered upon Fas/FasL binding [9]. Engagement of Fas induces oligomerization of preformed Fas trimers and recruits the Fas-associated death domain to form the death-inducing signaling complex (DISC). Caspases in the DISC initiate the apoptotic signaling cascade [10]

Results

Discussion

Conclusion