Anti-NMDA-receptor antibody encephalitis: Performance evaluation and laboratory experience with the anti-NMDA-receptor IgG assay

Suh-Lailam, Brenda B.; Haven, Thomas R.; Copple, Susan S.; Knapp, Diana; Jaskowski, Troy D.; Tebo, Anne E.

doi:10.1016/j.cca.2013.02.010

Cited by 53 publications

(45 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the presence of active germinal centers in the periphery, together with the higher absolute levels of NR1‐IgG in serum than CSF and the disease association with ovarian teratomas, all strongly support the initial peripheral generation of NR1 antibodies 2, 5. How the peripherally generated NR1‐specific cells cross the blood–brain barrier and are retained to produce relative intrathecal synthesis of NR1‐IgG, upon normalization for total IgG levels, is a separate question, and it may be that their activation in the periphery is sufficient to induce ligands which facilitate transmigration into the CNS.…”

Section: Discussionmentioning

confidence: 77%

“…Around 20% of patients have an associated ovarian teratoma which expresses the NR1 subunit of the NMDAR,3, 4 making this a likely site of primary immunization. This finding, together with the higher concentrations of NR1‐IgG in serum than CSF,2, 5 suggest that the autoantibodies are initially generated in the periphery. Indeed, especially given the recent description of NR1‐specific B cells and antibody‐secreting cells (ASCs) in the CSF, the consistent observation of NR1‐IgG intrathecal synthesis is most likely secondary to the cells, and some autoantibodies, crossing the blood–brain barrier after the primary systemic immunization 1, 2, 6, 7…”

mentioning

confidence: 87%

See 1 more Smart Citation

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

Makuch

Wilson

Al-Diwani

et al. 2018

Annals of Neurology

101

102

View full text Add to dashboard Cite

IntroductionN‐methyl‐D‐aspartate receptor (NMDAR) antibody encephalitis is mediated by immunoglobulin G (IgG) autoantibodies directed against the NR1 subunit of the NMDAR. Around 20% of patients have an underlying ovarian teratoma, and the condition responds to early immunotherapies and ovarian teratoma removal. However, despite clear therapeutic relevance, mechanisms of NR1‐IgG production and the contribution of germinal center B cells to NR1‐IgG levels are unknown.MethodsClinical data and longitudinal paired serum NR1‐reactive IgM and IgG levels from 10 patients with NMDAR‐antibody encephalitis were determined. Peripheral blood mononuclear cells from these 10 patients, and two available ovarian teratomas, were stimulated with combinations of immune factors and tested for secretion of total IgG and NR1‐specific antibodies.ResultsIn addition to disease‐defining NR1‐IgG, serum NR1‐IgM was found in 6 of 10 patients. NR1‐IgM levels were typically highest around disease onset and detected for several months into the disease course. Moreover, circulating patient B cells were differentiated into CD19+CD27++CD38++ antibody‐secreting cells in vitro and, from 90% of patients, secreted NR1‐IgM and NR1‐IgG. Secreted levels of NR1‐IgG correlated with serum NR1‐IgG (p < 0.0001), and this was observed across the varying disease durations, suggestive of an ongoing process. Furthermore, ovarian teratoma tissue contained infiltrating lymphocytes which produced NR1‐IgG in culture.InterpretationSerum NR1‐IgM and NR1‐IgG, alongside the consistent production of NR1‐IgG from circulating B cells and from ovarian teratomas suggest that ongoing germinal center reactions may account for the peripheral cell populations which secrete NR1‐IgG. Cells participating in germinal center reactions might be a therapeutic target for the treatment of NMDAR‐antibody encephalitis. Ann Neurol 2018;83:553–561

show abstract

Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 87%

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

Makuch

Wilson

Al-Diwani

et al. 2018

Annals of Neurology

101

102

View full text Add to dashboard Cite

show abstract

“…Their emotional behavioral disturbances may be associated with hypothalamic abnormality, reflecting no NMDAR autoimmunity involvement in our group. Previous data support that demyelinating episodes, especially NMO with AQP4 antibody, do not overlap with anti-NMDAR encephalitis [32]. Thus, whether patients with NMDAR encephalitis also have NMO/NMOSD is unclear.…”

Section: Discussionmentioning

confidence: 98%

No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders

Xie

Long²,

Yang³

et al. 2015

Neuroimmunomodulation

View full text Add to dashboard Cite

Objective: To evaluate whether serum glutamic acid decarboxylase (GAD), N-methyl-D-aspartate-receptor (NMDAR), and aquaporin-4 (AQP4) autoantibodies coexist in patients with neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD). Methods: Serum samples were collected from 98 patients with NMO/NMOSD. Serum GAD65, NMDAR and AQP4 antibodies were measured using a cell-based assay. Results: A total of 63 patients (64.3%) had myelitis and optic neuritis and satisfied the revised diagnostic criteria for NMO. Longitudinally extensive transverse myelitis was seen on spinal cord magnetic resonance imaging, showing continuous T2-weighted signal abnormalities in at least three vertebral segments in 26 patients (26.5%); 5 patients (5.1%) had recurrent optic neuritis, and 4 patients (4.1%) had brain syndromes with optic neuritis and myelitis. None of the 98 patients had diabetes, stiff-man syndrome, or epilepsy. All 98 patients tested positive for AQP4 antibody. No patients tested positive for GAD65 and NMDAR antibodies. Conclusions: In the present study, we found no simultaneous presence of serum GAD65, NMDAR and AQP4 antibodies in patients with NMO/NMOSD.

show abstract

“…Patient serum and CSF samples were obtained simultaneously and were maintained and transferred on ice to the laboratory. All specimens (serum and CSF) were evaluated for anti-NMDAR IgG antibodies by indirect immunofluorescence (IIF) using EU 90 cells transfected with the The NMDAR1 subunit (NR1) of the NMDAR complex and immobilized on BIOCHIPs (euroimmunAG, Lü beck, Germany) as previously described [7]. Slides were incubated with undiluted CSF samples or serum samples at a starting dilution of 1:10, and analysis was performed according to the manufacturer's guidelines.…”

Section: Determination Of Antibodies To Nmdarmentioning

confidence: 99%

CSF findings in patients with anti-N-methyl-d-aspartate receptor-encephalitis

Wang

Guan

Ren

et al. 2015

Seizure

View full text Add to dashboard Cite

show abstract

Anti-NMDA-receptor antibody encephalitis: Performance evaluation and laboratory experience with the anti-NMDA-receptor IgG assay

Cited by 53 publications

References 21 publications

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders

CSF findings in patients with anti-N-methyl-d-aspartate receptor-encephalitis

Contact Info

Product

Resources

About