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

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.

Relapse risk factors in anti‐N‐methyl‐D‐aspartate receptor encephalitis

“…In this respect, the correlation between anti-NMDAR antibodies and clinical course is unclear, 31,32 and the correlation of disease severity and relapse with other markers, such as C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif ligand 10 (CXCL10), Fas, Fas ligand, T-helper cell 17 (Th17), B cell activating factor from the tumor necrosis factor family (BAFF), and a proliferationinducing ligand (APRIL) is being investigated. [33][34][35][36][37][38][39] This dissociation between disease course (monophasic vs relapsing) and neurological outcome (mRS) at final followup is an interesting and counterintuitive finding. This result is limited by the statistically different length of follow-up between monophasic and relapsing patients (median 84mo and 32mo respectively), although it is mirrored by a previous analysis of relapses in anti-NMDAR encephalitis, with similar discrepancies in the length of follow-up in the two subgroups.…”

“…Indeed, it is unclear how long the inflammatory component of disease lasts. In this respect, the correlation between anti‐NMDAR antibodies and clinical course is unclear, and the correlation of disease severity and relapse with other markers, such as C‐X‐C motif chemokine ligand 13 (CXCL13), C‐X‐C motif ligand 10 (CXCL10), Fas, Fas ligand, T‐helper cell 17 (Th17), B cell activating factor from the tumor necrosis factor family (BAFF), and a proliferation‐inducing ligand (APRIL) is being investigated …”

HLA-A and HLA-DRB1 may play a unique role in ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis

“…To date, most studies have focused more on neurology or psychiatry rather than gynecology, and most have explored the etiology and pathogenesis of OT-associated NMDAR-E [ 9 ] by analyzing the biological and molecular differences in CSF and serum between teratoma patients with and without NMDAR-E [ 12 – 14 ]. Mueller et al reported only a borderline association of HLA-B*07:0 with NMDAR-E in German patients [ 15 ].…”

Anti‐N‐methyl‐D‐aspartate receptor encephalitis unresponsive to early and aggressive immunotherapy in a young female: A case report

“…6 Elevated CSF concentrations of soluble Fas and FasL were correlated with the changes in mRS score. 7 Unfortunately, these facilities are not available at our center, and the decision to 57% patients who failed first-line therapy received second-line immunotherapy (ie, rituximab, cyclophosphamide, or both) had better outcomes than those who continued first-line treatment or received no further immunotherapy. In the first 2 years, 394 of 501 reached good outcome and 30 died.…”

“…Cerebrospinal fluid has been analyzed for CXCL13, YKL-40, and soluble Fas and FasL in certain studies. [5][6][7] It was found that in patients who have been administered first-line drugs, detection of elevated CXCL13 levels in the CSF advocate the use of second-line immunotherapy. 5 Correlation of changes in CSF YKL-40 concentration with modified Rankin scale (mRS) score has been studied but it was found to be inconclusive.…”