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Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer

Department of Medicine B and Research Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer Israel, shoenfel{at}post.tau.ac.il

A Nahum

Department of Medicine B and Research Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer Israel

A D Korczyn

Department of Physiology & Pharmacology Sackler Faculty of Medicine, Tel Aviv, Israel, Department of Neurology and Neuroimmunology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

M Dano

Department of Neurology and Neuroimmunology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

R Rabinowitz

Department of Physiology & Pharmacology Sackler Faculty of Medicine, Tel Aviv, Israel

O Beilin

Department of Physiology & Pharmacology Sackler Faculty of Medicine, Tel Aviv, Israel

C G Pick

Department of Anatomy & Anthropology, Sackler Faculty of Medicine, Tel Aviv, Israel

L Leider-Trejo

Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

L Kalashnikova

Institute of Neurology, Moscow, Russia

M Blank

Department of Medicine B and Research Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer Israel

J Chapman

Department of Physiology & Pharmacology Sackler Faculty of Medicine, Tel Aviv, Israel, Department of Neurology and Neuroimmunology Service, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Antiphospholipid antibodies (aPL) have been suggested to play a role in causing cognitive and behavioral impairments. In the present study we investigated the pathogenic potential of aPL by intracerebro-ventricular (ICV) administration of immunoglobulins (IgG) from patients with antiphospholipid syndrome (APS). IgG, purified from the sera of four APS patients, was tested for binding to normal mouse brain by immunohistological staining. These IgG (7.5 m g) were injected ICV unilaterally to male C3H mice. Mice injected with IgG purified from pooled sera derived from healthy subjects served as controls. The mice were examined neurologically for motor function and coordination, and cognitively in a Morris water maze. The cognitive tests were performed with the experimenterblinded to the treatment. The performance of the mice in four separate experiments was compared by analysis of variance with repeated measures. IgG from one APS patient was found to bind best to neuronal structures in the hippocampus and cerebral cortex. Mice (n 43) injected with this IgG performed worse in the water maze compared to the controls(n 45) with significant effects of the aPL IgG on the overall performance of the mice (treatment, P < 0.03), on learning throughout the experiment (treatment xday, P < 0.02) and on short term memory (treatment xday xtrial, P < 0.002). IgG injected from two of the three other patients also bound specifically to mouse brain neurons and produced an impairment in performance of the water maze. These results support the hypothesis that aPL that gain access to the central nervous system may play a direct role in the pathogenesis of neurological manifestations of APS.

Key Words: anticardiolipin antibodies • antiphospholipid syndrome • autoantibodies • autoimmunity • cognitive impairment • experimental models

Lupus, Vol. 12, No. 6, 436-442 (2003)
DOI: 10.1191/0961203303lu409oa


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