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Front Immunol. 2016 Feb 1;7:5. doi: 10.3389/fimmu.2016.00005. eCollection 2016.

Antiglutamate Receptor Antibodies and Cognitive Impairment in Primary Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

Author information

1
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Division of Rheumatology, Lupus Clinic, Istituto Ortopedico Gaetano Pini, Milan, Italy.
2
Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano , Milan , Italy.
3
Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano , Milan , Italy.
4
Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano , Milan , Italy.
5
Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, UniversitĂ  degli Studi di Milano, Milan, Italy.
6
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy.
7
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Milan, Italy.
8
Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, University of Oklahoma , Oklahoma City, OK , USA.

Abstract

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome have an increased risk to develop cognitive impairment. A possible role for antiphospholipid antibodies (aPL) and antiglutamate receptor (anti-NMDA) antibodies in the pathogenesis of neurological manifestations of these two conditions, have been suggested. In particular, the role of anti-NMDA antibodies in the pathogenesis of neuropsychiatric SLE is supported by several experimental studies in animal models and by the finding of a correlation between anti-NMDA positivity in cerebrospinal fluid and neurological manifestations of SLE. However, data from the literature are controversial, as several studies have reported a correlation of these antibodies with mild cognitive impairment in SLE, but more recent studies have not confirmed this finding. The synergism between anti-NMDA and other concomitant autoantibodies, such as aPL, can be hypothesized to play a role in inducing the tissue damage and eventually the functional abnormalities. In line with this hypothesis, we have found a high incidence of at least one impaired cognitive domain in a small cohort of patients with primary APS (PAPS) and SLE. Interestingly, aPL were associated with low scoring for language ability and attention while anti-NMDA titers and mini-mental state examination scoring were inversely correlated. However, when patients were stratified according to the presence/absence of aPL, the correlation was confirmed in aPL positive patients only. Should those findings be confirmed, the etiology of the prevalent defects found in PAPS patients as well as the synergism between aPL and anti-NMDA antibodies would need to be explored.

KEYWORDS:

anti-NMDA/glutamate receptor antibodies; antiphospholipid syndrome; central nervous system involvement; mild cognitive impairment; neuropsychological assessment; systemic lupus erythematosus

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