Intractable Headaches, Ischemic Stroke, and Seizures Are Linked to the Presence of Anti-β2GPI Antibodies in Patients with Systemic Lupus Erythematosus

PLOS ONE, Dec 2019

Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and potentially fatal manifestation of SLE. Antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL) and antibodies to β2glycoprotein I (anti-β2GPI), the most important aPL antigen, are thought to play a role in some forms of NPSLE. As of yet, their specific roles in NPSLE manifestations remain to be elucidated. Methodology/Principal Findings 57 SLE patients (53 women) were assessed for LA, aCL and anti-β2GPI twice, to determine persistent positivity. All patients were examined by neurology and psychiatry specialists. 69 healthy subjects were assessed as controls. NPSLE was diagnosed in 74% of patients. Headaches were the most prevalent manifestation of NPSLE (39%), followed by cerebrovascular disease (CVD) (23%), depressive disorders (19.0%), and seizures (14%). NPSLE and non-NPSLE patients showed comparable SLE activity and corticosteroid use. In 65% of patients neuropsychiatric manifestations preceded SLE diagnosis. aPL profiles of NPSLE patients and non-NPSLE patients were similar. Headaches and ischemic stroke were independently associated with anti-β2GPI-IgM (OR=5.6; p<0.05), and seizures were linked to anti-β2GPI-IgG (OR=11.3; p=0.01). Conclusions In SLE patients, neuropsychiatric manifestations occur frequently and early, often before the disease is diagnosed. Autoantibodies to β2GPI are linked to non-specific headaches, ischemic stroke and seizures, and show a better predictive value than aCL and LA. These findings may help to improve the diagnosis of NPSLE and should prompt further studies to characterize the role of anti-β2GPI in the pathogenesis of this condition.

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Intractable Headaches, Ischemic Stroke, and Seizures Are Linked to the Presence of Anti-β2GPI Antibodies in Patients with Systemic Lupus Erythematosus

March Intractable Headaches, Ischemic Stroke, and Seizures Are Linked to the Presence of Anti- 2GPI Antibodies in Patients with Systemic Lupus Erythematosus Tomasz Hawro 0 1 2 Andrzej Bogucki 0 1 2 Maria Krupiska-Kun 0 1 2 Marcus Maurer 0 1 2 Anna Woniacka 0 1 2 0 1 Department of Dermatology and Allergy , Charite-Universitatsmedizin Berlin, Berlin, Germany , 2 Department of Extrapyramidal Diseases, Medical University of odz, odz, Poland, 3 Department of Affective and Psychotic Disorders, Medical University of odz, odz, Poland, 4 Department of Dermatology and Venereology, Medical University of odz , odz , Poland 1 Funding: This work was funded by the grant from the Medical University of Lodz nr. 503/1-152-01/503-01. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript 2 Academic Editor: Jose Crispin, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran , MEXICO - Competing Interests: The authors have declared that no competing interests exist. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and potentially fatal manifestation of SLE. Antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL) and antibodies to 2glycoprotein I (anti-2GPI), the most important aPL antigen, are thought to play a role in some forms of NPSLE. As of yet, their specific roles in NPSLE manifestations remain to be elucidated. Methodology/Principal Findings 57 SLE patients (53 women) were assessed for LA, aCL and anti-2GPI twice, to determine persistent positivity. All patients were examined by neurology and psychiatry specialists. 69 healthy subjects were assessed as controls. NPSLE was diagnosed in 74% of patients. Headaches were the most prevalent manifestation of NPSLE (39%), followed by cerebrovascular disease (CVD) (23%), depressive disorders (19.0%), and seizures (14%). NPSLE and non-NPSLE patients showed comparable SLE activity and corticosteroid use. In 65% of patients neuropsychiatric manifestations preceded SLE diagnosis. aPL profiles of NPSLE patients and non-NPSLE patients were similar. Headaches and ischemic stroke were independently associated with anti-2GPI-IgM (OR=5.6; p<0.05), and seizures were linked to anti-2GPI-IgG (OR=11.3; p=0.01). In SLE patients, neuropsychiatric manifestations occur frequently and early, often before the disease is diagnosed. Autoantibodies to 2GPI are linked to non-specific headaches, ischemic stroke and seizures, and show a better predictive value than aCL and LA. These findings may help to improve the diagnosis of NPSLE and should prompt further studies to characterize the role of anti-2GPI in the pathogenesis of this condition. Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease with autoantibody-mediated tissue damage. Clinically, SLE is characterized by heterogeneous symptoms and may involve almost all tissues and organs, including the nervous system. Neuropsychiatric lupus encompasses a wide spectrum of neurologic and psychiatric disorders resulting from the involvement of the central, peripheral and autonomic nervous system due to SLE-related pathology. The attribution of different neurologic and psychiatric disorders to neuropsychiatric SLE (NPSLE) is still a matter of debate. NPSLE is a relatively frequent and potentially fatal presentation of SLE, and the involvement of CNS especially is associated with a more serious course and increased mortality [13]. The pathogenesis of NPSLE remains largely unclear, but the occlusion of vessels supplying the nervous tissue and direct interaction of antibodies with phospholipids of neural cells appear to be important. Antiphospholipid antibodies (aPL) may contribute to both of these pathogenic mechanisms [46]. aPL are a heterogeneous group of autoantibodies, such as anticardiolipin antibodies (aCL), lupus anticoagulant (LA) and anti-2-glycoprotein-I (anti-2GPI), that are frequently observed in autoimmune disorders, especially in SLE. aPL share the ability to bind to phospholipid binding proteins or to complexes of these proteins with phospholipids. 2GPI is the most important aPL antigen [7]. In recent years, the role and relevance of anti-2GPI in autoimmune conditions have been better characterized. The presence of anti-2GPI was included in the list of diagnostic criteria for antiphospholipid syndrome (APS) and, recently, in the Systemic Lupus International Collaborating Clinics classification criteria for SLE [8, 9]. Nonetheless, little is known about the frequency of expression of anti-2GPI in NPSLE, and their role in its pathology. The aim of the study was to evaluate NPSLE and non-NPSLE patients for the presence of anti-2GPI and other aPL such as aCL and LA and to assess the association between these antibodies and the presence of NPSLE disorders. Materials and Methods Subjects and diagnostic measures This study was approved by the local Ethics Committee and conducted i (...truncated)


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Tomasz Hawro, Andrzej Bogucki, Maria Krupińska-Kun, Marcus Maurer, Anna Woźniacka. Intractable Headaches, Ischemic Stroke, and Seizures Are Linked to the Presence of Anti-β2GPI Antibodies in Patients with Systemic Lupus Erythematosus, PLOS ONE, 2015, Volume 10, Issue 3, DOI: 10.1371/journal.pone.0119911