Association between Lupus Psychosis and Antiribosomal P Protein Antibodies

Bonfá, Eloísa; Golombek, Steven J.; Kaufman, Lee D.; Skelly, Susan; Weissbach, Herbert; Brot, Nathan; Elkon, Keith B.

doi:10.1056/nejm198707303170503

Cited by 553 publications

(332 citation statements)

References 33 publications

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“…It is therefore possible that anti-NR2 antibodies might also be produced within the CNS, leading to their elevation in CSF and to neuronal damage. In contrast, anti-ribosomal P (anti-P) antibodies in the serum have been shown to be associated with diffuse NPSLE (4,16,19). We have recently demonstrated that anti-P antibodies up-regulate the expression of tumor necrosis factor ␣ protein and messenger RNA in human peripheral blood monocytes (20).…”

Section: Discussionmentioning

confidence: 99%

Association of cerebrospinal fluid anti–NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus

Arinuma¹,

Yanagida²,

Hirohata³

2008

Arthritis & Rheumatism

224

130

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Results. Purified anti-NR2 bound to the surface of SK-N-MC cells. Levels of anti-NR2 antibodies in CSF were significantly elevated in patients with diffuse NPSLE compared with levels in control patients or those with focal NPSLE, whereas there were no significant differences in serum anti-NR2 levels among the 3 groups. In 31 of the 38 patients with diffuse NPSLE (81.6%) and 8 of the 18 patients with focal NPSLE (44.4%), CSF anti-NR2 levels were more than 3 SD above the mean level in the control patients (P ‫؍‬ 0.0120 by chi-square test). Conclusion.These results indicate that anti-NR2 is a constituent of antineuronal antibodies and, more importantly, that anti-NR2 antibodies in CSF, but not in serum, are associated with diffuse NPSLE.

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Section: Discussionmentioning

confidence: 99%

Association of cerebrospinal fluid anti–NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus

Arinuma¹,

Yanagida²,

Hirohata³

2008

Arthritis & Rheumatism

224

130

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“…In a seminal study published over 20 years ago, antiribosomal P autoantibodies were detected in 90% of patients with SLE and psychosis, 45 and recent work suggests that this antibody might cross-react with a neuronal surface protein to initiate calcium influx and apoptosis. 46 However, large clinical studies and meta-analyses have reached variable results with regard to the presence of antiribosomal P antibodies in neuropsychiatric SLE, with differences attributed to laboratory methodology, study population, fluctuating course of disease, and diagnostic discrepancies.…”

Section: Encephalopathy In Lupus and Other Systemic Syndromesmentioning

confidence: 99%

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

Kayser¹,

Dalmau²

2011

Journal of Neuropsychiatry

115

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“…Accordingly, anti-P antibodies also up-regulated the expression of TNF␣ and IL-6 messenger RNA in activated monocytes. Of note, F(ab ) 2 …”

mentioning

confidence: 99%

Anti–ribosomal P protein antibody in human systemic lupus erythematosus up‐regulates the expression of proinflammatory cytokines by human peripheral blood monocytes

Nagai¹,

Arinuma²,

Yanagida³

et al. 2005

Arthritis & Rheumatism

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Objective. Autoantibodies to ribosomal P proteins (anti-P antibodies) are detected in 12-16% of patients with systemic lupus erythematosus (SLE) and have been found to be associated with some manifestations of the disease, including lupus psychosis and hepatitis. Recent studies have disclosed that anti-P antibodies react with activated T cells but not with B cells, suggesting possible direct effects of anti-P antibodies on immune regulation. The present study was designed to explore the presence of the epitope recognized by anti-P antibodies on human peripheral blood monocytes.Methods. Highly purified peripheral blood monocytes obtained from healthy donors were cultured with or without interferon-␥ (IFN␥) in the presence of either anti-P antibodies purified by affinity chromatography from the sera of patients with SLE or control IgG.Results. Flow cytometry analysis disclosed that fresh (day 0) monocytes did not express the ribosomal P epitope, whereas expression of the ribosomal P epitope was induced on annexin V-negative monocytes after activation through plastic adherence for 48 hours. More important, anti-P antibodies (compared with normal IgG or IgG from SLE patients devoid of anti-P antibodies) enhanced the production of tumor necrosis factor ␣ (TNF␣) and interleukin-6 (IL-6) by activated monocytes. Accordingly, anti-P antibodies also up-regulated the expression of TNF␣ and IL-6 messenger RNA in activated monocytes. Of note, F(ab ) 2 fragments of anti-P antibodies, which do not result in Fc␥ receptor (Fc␥R) crosslinking, also effectively up-regulated the expression of TNF␣ and IL-6.Conclusion. These results indicate that human peripheral blood monocytes express the ribosomal P epitope upon activation, irrespective of induction of apoptosis. Moreover, the data suggest that anti-P antibodies might modify a variety of inflammatory responses through up-regulation of the expression of proinflammatory cytokines in monocytes, in a manner that does not involve Fc␥R crosslinking.Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the expression of a variety of autoantibodies. Autoantibodies to ribosomal P proteins (anti-P antibodies) are detected in 12-16% of patients with SLE (1). Anti-P antibodies are directed to 3 phosphoproteins (P0, P1, and P2), which are located on the larger 60S subunit of eukaryotic ribosomes and have molecular weights of 38 kd, 19 kd, and 17 kd, respectively (1). Ribosomal P proteins share a common linear determinant that is present in the carboxyl-terminal 22-amino acid sequence (1). Previous and recent studies have disclosed the association of anti-P antibodies with neuropsychiatric disease in SLE (2,3). Moreover, it was recently shown that antiribosomal P is strongly associated with hepatitis and

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Association between Lupus Psychosis and Antiribosomal P Protein Antibodies

Cited by 553 publications

References 33 publications

Association of cerebrospinal fluid anti–NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus

Association of cerebrospinal fluid anti–NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

Anti–ribosomal P protein antibody in human systemic lupus erythematosus up‐regulates the expression of proinflammatory cytokines by human peripheral blood monocytes

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