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. 2005 Feb 11;64(8):1210–1213. doi: 10.1136/ard.2004.029280

Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus

E Husebye 1, Z Sthoeger 1, M Dayan 1, H Zinger 1, D Elbirt 1, M Levite 1, E Mozes 1
PMCID: PMC1755620  PMID: 15708887

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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Figure 1.

Figure 1

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 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 type I (APS1), and 65 healthy controls were tested. NR2A specific antibodies were determined by enzyme linked immunosorbent assay (ELISA). Results are expressed as NR2A antibody indices, calculated as described in Methods. The horizontal line represents the upper normal limit (NR2A antibody index of 30) defined as the mean of 65 normal controls +2SD. *p<0.001, **p<0.02.

Figure 2.

Figure 2

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 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 patients (two or more serum samples per patient). The line represents the linear regression. dsDNA, double stranded deoxyribonucleic acid.

Figure 3.

Figure 3

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 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, C) during a follow up period of 18 to 33 months. dsDNA, double stranded deoxyribonucleic acid.

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