Identification of novel autoantibodies to GABA(B) receptors in patients with neuropsychiatric systemic lupus erythematosus

Rheumatology (Oxford). 2014 Jul;53(7):1219-28. doi: 10.1093/rheumatology/ket481. Epub 2014 Mar 4.

Abstract

Objective: The gamma-aminobutyric acid type B receptors (GABAR(B)) are G-protein coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. We identified GABAR(B) subunits as candidate antigens in patients with SLE using a random peptide display library. The aim of this study was to investigate the possible link between anti-GABAR(B) antibodies and disease activity and NPSLE.

Methods: ELISA was performed with recombinant proteins of GABAR(B1b) and GABAR(B2) on serum samples from patients with SLE (n = 88), scleroderma (n = 20), myositis (n = 20) or vasculitis (n = 20) as well as healthy subjects (n = 20). Cerebrospinal fluid (CSF) from 23 patients with SLE was also examined.

Results: Autoantibodies to GABAR(Bs) were exclusive to patients with SLE (P < 0.001) and positively associated with SLEDAI (anti-GABAR(B1b), P = 0.001; anti-GABAR(B2), P < 0.001). Of note, autoantibodies were positively linked with NPSLE (anti-GABAR(B1b), P = 0.02; anti-GABAR(B2), P = 0.03). Moreover, anti-GABAR(Bs) was detected in 61.5% of CSF samples from patients with active NPSLE, a frequency that was significantly higher than that for patients with non-SLE syndromes.

Conclusion: Anti-GABAR(B) antibodies could represent novel candidate markers for disease activity and NPSLE.

Keywords: GABAB receptor; autoantibody; disease activity; neuropsychiatric systemic lupus erythematosus; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Female
  • Humans
  • Lupus Vasculitis, Central Nervous System / diagnosis*
  • Lupus Vasculitis, Central Nervous System / immunology
  • Lupus Vasculitis, Central Nervous System / metabolism
  • Male
  • Middle Aged
  • Receptors, GABA-B / immunology*
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Biomarkers
  • Receptors, GABA-B