Accuracy of anti–ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: An international meta‐analysis

Abstract

Objective. To quantitatively evaluate the diagnostic accuracy of antibodies to ribosomal P proteins (anti-P) for neuropsychiatric systemic lupus erythematosus (NPSLE) in general, for psychosis, mood disorder, or both, and for other diffuse manifestations.Methods. This international meta-analysis combined standardized data from 1,537 lupus patients contributed by 14 research teams. Weighted estimation of sensitivity and specificity with fixed-effects and random-effects models, as well as summary receiver operating characteristic (SROC) curve analysis, was used to summarize test performance. The robustness of the overall estimates was examined in sensitivity analyses that included additional studies published up to November 1, 2004 in the Medline, EMBase, and Cochrane databases.Results. Combining the data from the 14 teams, the weighted sensitivity and specificity estimates for the diagnosis of NPSLE were 26% (95% confidence interval [95% CI] 15-42%) and 80% (95% CI 74-85%), respectively. For psychosis, mood disorder, or both, the sensitivity and specificity were 27% (95% CI 14-47%) and 80% (95% CI 74-85%), respectively. For other diffuse manifestations, the sensitivity was 24% (95% CI 12-42%), and the specificity was 80% (95% CI 73-85%). The proportion of patients with anti-P antibodies did not vary markedly across different presentations of NPSLE. Between-study heterogeneity was substantial, but the SROC curves were consistent with the weighted estimates. In further analyses that included another 24

Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study

“…With regard to autoantibodies, the current data suggest that aPL cause focal NP disease (e.g., stroke, seizures) by promoting intravascular thrombosis (5). In contrast, anti-P antibodies (21,22), and possibly anti-NR2 antibodies (13,15), cause diffuse NP events (e.g., psychosis, depression, cognitive impairment) through a direct effect on neuronal cells; a critical factor in this is the ability of these antibodies to directly access neuronal cells either through intrathecal production or via passage from the circulation across a permeabilized blood-brain barrier.…”

“…The most direct evidence supporting the hypothesis of autoantibody involvement in NPSLE is derived from studies of animal models (13)(14)(15)(16)(17), whereas evidence from human studies is frequently conflicting or inconclusive (18)(19)(20)(21)(22). This may be due in part to methodologic difficulties involving, for example, selection of patients for study, lack of rigor in the characterization of NP events, and differences between laboratories in assay techniques.…”

“…The latter include antiphospholipid antibodies (aPL), antiribosomal P antibodies (anti-P), and autoantibodies that bind to neuronal antigens such as the recently described antibodies to the NR2 glutamate receptor (13). Although there is biologic plausibility and data from in vitro studies and animal studies to implicate these autoantibodies in the causality of nervous system disease (13)(14)(15)(16)(17), studies of humans with SLE have yielded inconsistent findings (18)(19)(20)(21)(22). Previous investigations have been limited by their cross-sectional study design, heterogeneity of study patients in terms of disease duration, and lack of standardization in both the classification of NP events and the methodology used for autoantibody detection.…”

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

“…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. 47,48 Other groups have reported that a subset of anti-DNA antibodies in SLE cross-react with NMDA receptors, potentially resulting in neuropsychiatric abnormalities. 49 In contrast with anti-NMDA receptor encephalitis, the autoantibodies in SLE recognized the NR2A and NR2B subunits of the NMDA receptor, 49 which are developmentally regulated and highly expressed in hippocampus.…”

Actualización en lupus neuro-psiquiátrico con énfasis en déficit cognitivo

“…Se encuentran de 5% a 13% de los pacientes con LES. Son específicos de LES, y se han relacionado con LESNP en globo (psicosis lúpica y trastornos depresivos), pero con una potencia predictora dé-bil 21,34,[44][45][46][47][48] . Recientemente, Matus et al, trabajando en nuestro laboratorio, identificaron un autoanticuerpo proveniente de una paciente con psicosis lúpica dirigido contra un antígeno P ubicado en la superficie neuronal (llamado NSPA por sus siglas en inglés), reconocido por autoanticuerpos anti-P 49 .…”