Seroprevalence of autoantibodies against brain antigens in health and disease

Ann Neurol. 2014 Jul;76(1):82-94. doi: 10.1002/ana.24189. Epub 2014 Jun 23.


Objective: We previously reported an unexpectedly high seroprevalence (~10%) of N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1) autoantibodies (AB) in healthy and neuropsychiatrically ill subjects (N = 2,817). This finding challenges an unambiguous causal relationship of serum AB with brain disease. To test whether similar results would be obtained for other brain antigen-directed AB previously connected with pathological conditions, we systematically screened serum samples of 4,236 individuals.

Methods: Serum samples of healthy (n = 1,703) versus neuropsychiatrically ill subjects (schizophrenia, affective disorders, stroke, Parkinson disease, amyotrophic lateral sclerosis, personality disorder; total n = 2,533) were tested. For analysis based on indirect immunofluorescence, we used biochip mosaics of frozen brain sections (rat, monkey) and transfected HEK293 cells expressing respective recombinant target antigens.

Results: Seroprevalence of all screened AB was comparable in healthy and ill individuals. None of them, however, reached the abundance of NMDAR1 AB (again ~10%; immunoglobulin [Ig] G ~1%). Appreciable frequency was noted for AB against amphiphysin (2.0%), ARHGAP26 (1.3%), CASPR2 (0.9%), MOG (0.8%), GAD65 (0.5%), Ma2 (0.5%), Yo (0.4%), and Ma1 (0.4%), with titers and Ig class distribution similar among groups. All other AB were found in ≤0.1% of individuals (anti-AMPAR-1/2, AQP4, CV2, Tr/DNER, DPPX-IF1, GABAR-B1/B2, GAD67, GLRA1b, GRM1, GRM5, Hu, LGl1, recoverin, Ri, ZIC4). The predominant Ig class depended on antigen location, with intracellular epitopes predisposing to IgG (chi-square = 218.91, p = 2.8 × 10(-48) ).

Interpretation: To conclude, the brain antigen-directed AB tested here are comparably detectable in healthy subjects and the disease groups studied here, thus questioning an upfront pathological role of these serum AB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood*
  • Female
  • Germany / epidemiology
  • HEK293 Cells
  • Haplorhini
  • Humans
  • Male
  • Mass Screening
  • Mental Disorders / blood*
  • Mental Disorders / epidemiology*
  • Mental Disorders / immunology
  • Middle Aged
  • Nervous System Diseases / blood*
  • Nervous System Diseases / epidemiology*
  • Nervous System Diseases / immunology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Reference Values
  • Seroepidemiologic Studies


  • Autoantibodies
  • NMDA receptor A1
  • Receptors, N-Methyl-D-Aspartate