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Ann Rheum Dis. 2005 August; 64(8): 1210–1213.
Published online 2005 February 11. doi:  10.1136/ard.2004.029280
PMCID: PMC1755620
Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus
E Husebye, Z Sthoeger, M Dayan, H Zinger, D Elbirt, M Levite, and E Mozes
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract
Objective: To determine the prevalence of autoantibodies directed against an epitope of the glutamate/N-methyl-D-aspartic acid (NMDA) receptor subunit NR2A (which is highly expressed in human brain) in the sera of lupus patients, and to investigate the possible correlation of these antibodies with clinical and serological manifestations of systemic lupus erythematosus (SLE).
Methods: Sera were obtained from 109 consecutive SLE patients. Controls were 65 patients with myasthenia gravis, 19 with autoimmune polyendocrine syndrome type I (APS I), and 65 healthy donors. A 15 amino acid long peptide based on a sequence within the NR2A subunit of the NMDA/glutamate receptor was synthesised. Antibodies to this peptide were determined by enzyme linked immunosorbent assay. Antibodies against double stranded DNA (dsDNA) were measured by Chrithidia luciliae assay. Disease activity was determined using the SLE disease activity index (SLEDAI).
Results: Sera of 34/109 SLE patients (31%) reacted specifically with the NR2A peptide compared with only 4/65 myasthenia gravis patients (6.1%, p<0.001), 1/19 APS I patients (5.3%, p<0.02), and 3/65 healthy controls (4.6%, p<0.001). No correlation was found between the presence of NR2A and dsDNA or anti-cardiolipin specific autoantibodies. In addition, no significant correlation was observed between the presence of NR2A specific antibodies and the SLEDAI score or any lupus related clinical manifestations.
Conclusions: A significant number of SLE patients (31%) have NR2A specific antibodies that do not correlate with anti-dsDNA antibodies. Additional studies of lupus patients with neurological disorders should elucidate the role of NR2A specific antibodies in lupus related CNS manifestations.
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Selected References
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Figures and Tables
Figure 1
Figure 1
 Antibodies against the NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus (SLE). Sera from 109 SLE patients, 65 patients with myasthenia gravis (MG), 19 patients with autoimmune polyendocrine syndrome (more ...)
Figure 2
Figure 2
 Correlation between NR2A antibody indices and dsDNA reactivity in sera of patients with systemic lupus erythematosus (SLE). The NR2A antibody indices and dsDNA antibody reactivity (negative to +4) were compared in 125 serum samples from 59 SLE (more ...)
Figure 3
Figure 3
 Correlation between NR2A antibody indices, dsDNA specific antibodies, and systemic lupus erythematosus disease activity index (SLEDAI). NR2A antibody index, dsDNA reactivity, and SLEDAI were determined in three different SLE patients (A, B, (more ...)