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

Abstract

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-beta2-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.

Figure 1

Frequency of autoantibodies in SLE inception cohort. The upper panel illustrates the proportion of all SLE patients with autoantibodies and the lower panel illustrates the frequency of autoantibodies in patients with and without neuropsychiatric (NP) events from all causes. LA = lupus anticoagulant; aCL = IgG anticardiolipin antibody; aBeta-2 = anti-β₂-glycoprotein I; anti-P = anti-ribosomal P antibody; aNR2 = anti-NR2 glutamate receptor antibody; aDNA = anti-DNA antibody.

Figure 2

The frequency of autoantibodies in SLE patients with and without neuropsychiatric (NP) events. Four mutually exclusive groups were examined: patients with NP events attributed to SLE who qualify under model A (NP-SLE (A)), patients with NP events attributed to SLE who qualify under model B but not model A (NP-SLE (B not A)), patients with NP events attributed to non-SLE causes (NP (non-SLE)) and patients with no NP events (No NP events). Model A: The onset of NP events prior to the enrollment window, the identification of any non-SLE factors which contributed to or were responsible for the NP event or the occurrence of a “minor” NP event as defined by Ainiala et al (1) indicated that the NP event was not attributed to SLE. Model B: The onset of NP events more than 10 years prior to the diagnosis of SLE, the identification of non-SLE factors which were responsible for the NP event (“exclusion factors” only) or the occurrence of a “minor” NP event as defined by Ainiala et al (1) indicated that the NP event was not attributed to SLE. LA = lupus anticoagulant; aCL = IgG anticardiolipin antibody; aBeta-2 = anti-β₂- glycoprotein I; anti-P = anti-ribosomal P antibody; aNR2 = anti-NR2 glutamate receptor antibody; aDNA = anti-DNA antibody.

Figure 3

The frequency of anti-ribosomal P antibodies in SLE patients with and without central (upper panel) and diffuse (lower panel) neuropsychiatric (NP) events. Central NP manifestations have been previously described (26). Diffuse NP syndromes were identified as aseptic meningitis, demyelinating syndrome, headache, acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder and psychosis. Four mutually exclusive groups were examined: patients with NP events attributed to SLE who qualify under model A (NP-SLE (A)), patients with NP events attributed to SLE who qualify under model B but not model A (NP-SLE (B not A)), patients with NP events attributed to non-SLE causes (NP (non-SLE)) and patients with no NP events (No NP events). Model A: The onset of NP events prior to the enrollment window, the identification of any non-SLE factors which contributed to or were responsible for the NP event or the occurrence of a “minor” NP event as defined by Ainiala et al (1) indicated that the NP event was not attributed to SLE. Model B: The onset of NP events more than 10 years prior to the diagnosis of SLE, the identification of non-SLE factors which were responsible for the NP event (“exclusion factors” only) or the occurrence of a “minor” NP event as defined by Ainiala et al (1) indicated that the NP event was not attributed to SLE.