title: Anti-NMDA-receptor antibody encephalitis: performance evaluation and laboratory experience with the anti-NMDA-receptor IgG assay.
abstract: BACKGROUND
  Antibodies targeting the NR1 subunit of the N-methyl-d-aspartate-receptor (NMDAR) are considered diagnostic for a novel form of autoimmune encephalitis. We report the validation of a qualitative indirect immunofluorescence antibody (IFA) test for the detection of anti-NMDAR IgG and describe the attributes of antibody-positive patients.
  
  
  METHODS
  The anti-NMDAR IgG assay (Euroimmun Diagnosika, Lübeck, Germany) was validated with serum and cerebrospinal fluid (CSF) specimens from 30 healthy and 50 disease controls as well as 5 anti-NMDAR IgG-positive individuals. Consecutive specimens (n=1671) for anti-NMDAR IgG antibodies were evaluated and positive specimens titrated to end-point [starting dilutions: CSF; 1:1 and serum; 1:10]. In a subset of antibody-positive patients, we sought clinical information for correlation with diagnostic and treatment outcomes.
  
  
  RESULTS
  The assay demonstrated excellent performance characteristics in all groups evaluated. Of the 1671 specimens tested, 1389 were unique cases with a positivity rate of 9.0% (n=123). For the antibody-positive samples, the female to male ratio was 2:1 with a prevalence of 46% in the pediatric population (≤17 years). Antibody titers were titrated to end-point for 106/123 specimens [45 CSF, 41 sera, and 20 CSF and serum pairs] with more than 75% having titers greater than 1:10 (CSF) and 1:20 (serum). Overall, high levels of these antibodies showed correlation to disease severity with variable response to treatment in the subset of patients evaluated.
  
  
  CONCLUSIONS
  Our data suggests a high prevalence for anti-NMDAR antibody encephalitis irrespective of age and gender in our unselected disease cohort with support for measuring antibody titers in the evaluation of these patients.
authors: ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, United States.
authors: Brenda B
authors: BB
authors: Suh-Lailam
authors: Thomas R
authors: TR
authors: Haven
authors: Susan S
authors: SS
authors: Copple
authors: Diana
authors: D
authors: Knapp
authors: Troy D
authors: TD
authors: Jaskowski
authors: Anne E
authors: AE
authors: Tebo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000592:standards*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D016194:Receptors, N-Methyl-D-Aspartate