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

• Published in: Arthritis and rheumatism Vol. 58; no. 3; pp. 843 - 853
• Main Authors: Hanly, J. G., Urowitz, M. B., Siannis, F., Farewell, V., Gordon, C., Bae, S. C., Isenberg, D., Dooley, M. A., Clarke, A., Bernatsky, S., Gladman, D., Fortin, P. R., Manzi, S., Steinsson, K., Bruce, I. N., Ginzler, E., Aranow, C., Wallace, D. J., Ramsey‐Goldman, R., van Vollenhoven, R., Sturfelt, G., Nived, O., Sanchez‐Guerrero, J., Alarcón, G. S., Petri, M., Khamashta, M., Zoma, A., Font, J., Kalunian, K., Douglas, J., Qi, Q., Thompson, K., Merrill, J. T.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2008; Wiley
• Subjects: Adult; Antibodies, Anticardiolipin - blood; Autoantibodies - blood; beta 2-Glycoprotein I - immunology; Biological and medical sciences; Cohort Studies; Diseases of the osteoarticular system; Female; Humans; International Cooperation; Lupus Coagulation Inhibitor - immunology; Lupus Vasculitis, Central Nervous System - diagnosis; Lupus Vasculitis, Central Nervous System - immunology; Lupus Vasculitis, Central Nervous System - psychology; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Receptors, Glutamate - immunology; Ribosomal Proteins - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Autoimmunity; Immunopathology; Connective tissue disease; Skin disease; Systemic lupus erythematosus; Cohort study; Systemic disease; Rheumatology; Autoantibody; Autoimmune disease; Diagnosis
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.23218

Objective
To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti–ribosomal P (anti‐P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti–β2‐glycoprotein I, and anti–NR2 glutamate receptor antibodies.
Methods
NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution.
Results
Four hundred twelve patients were studied (87.4% female; mean ± SD age 34.9 ± 13.5 years, mean ± SD disease duration 5.0 ± 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti‐P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti‐P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P = 0.02). Specific clinical–serologic associations were found between anti‐P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events.
Conclusion
Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti‐P antibodies and LAC. This suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.