Objective: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. Methods: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). Results: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. Conclusion: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research. Lupus (2016) 25, 878-888.

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Purpose To evaluate the use of immunosuppressive treatment, clinical outcome and diagnostic strategy in patients with systemic lupus erythematosus (SLE) presenting with clinical features of transverse myelitis (TM), but normal MRI of the spinal cord (sMRI) and normal cerebrospinal fluid (CSF) assessment, and to suggest a clinical guideline. Patients and Methods All patients with SLE and clinical features compatible with (sub)acute TM visiting the NPSLE clinic of the LUMC between 2007 and 2020 were included. Information on baseline characteristics, investigations, treatment and outcomes was collected from electronic medical records. In addition, a systematic review of individual participant data was performed up to April 2020 in PubMed, Embase and Web of Science, identifying all patients with TM, SLE and sMRI assessment. Data regarding sMRI, CSF analysis, treatment and outcome were extracted, and outcome was compared between patients with normal sMRI and CSF (sMRI-/CSF-) and patients with abnormalities. Results Twelve SLE patients with a clinical diagnosis of TM were identified: four sMRI-/CSF- and one sMRI- with CSF not available. All patients received immunosuppressive treatment, but outcome in sMRI-/CSF- patients was worse: no recovery (n=1) or partial recovery (n=3) compared to partial recovery (n=4) and (nearly) complete recovery (n=3) in MRI+ patients. The systematic literature review yielded 146 articles eligible for inclusion, 90% case reports. A total of 427 SLE patients with TM were identified, of which only four cases were sMRI-/CSF- (1%), showing no improvement (n=1), partial improvement (n=2) and complete recovery (n=1) after immunosuppressive treatment. Conclusion Outcome in SLE patients presenting with clinically suspected TM with normal sMRI and CSF is less favorable, despite treatment with immunosuppressive therapy. Taking a functional neurological disorder into consideration may be helpful in order to start other therapeutic strategies. We suggest prescribing immunosuppressive treatment for a restricted period of time to evaluate its effect in cases where a functional disorder initially is considered unlikely.

BackgroundNew ACR-EULAR SLE criteria have been proposed in order to attempt to improve classification for clinical and translational research (1, 2).ObjectivesWe evaluated the performance of the proposed 2017 ACR-EULAR classification criteria in a cohort of SLE patients with neuropsychiatric (NP) symptoms and compared to previous classification criteria.MethodsMedical records of patients visiting the NPSLE clinic of the Leiden University Medical Center (LUMC) between 2007-2017 were retrospectively evaluated. The performance of the proposed 2017 ACR-EULAR criteria, the 2012 SLICC criteria and the 1997 ACR criteria was evaluated by calculating sensitivity and specificity.Results360 patients were included, of which 294 were clinically diagnosed with SLE. The newly proposed 2017 ACR-EULAR showed a sensitivity of 87% (95% CI: 83-91%) and a specificity of 74% (95% CI: 62-84%), as shown in Table 1. The 2012 SLICC criteria had a sensitivity of 85% (95% CI: 80-89%) and a specificity of 76% (95% CI: 64-85%). The 1997 ACR criteria had a sensitivity of 89% (95% CI: 85-92%) and a specificity of 89% (95% CI: 80-96%).Sixty out of 294 patients fulfilled the proposed NP domain (delirium/psychosis/epilepsy). Using more specific criteria for NP symptoms related to SLE, as previously proposed by Bortoluzzi et al . (3), only 37 patients fulfilled this domain. However, this did not improve specificity, which remained 74% (95% CI: 62-84%).In addition, the performance of the newly proposed criteria was evaluated including patients with more than 10 points, but negative ANA. This led to an increase of sensitivity to 90% (95% CI 86-94%), but also did not influence specificity. Proposed 2017 ACR-EULAR classification criteria in SLE patients with NP symptoms With adjusted NP domain Including ANA negative patients Sensitivity (95% CI) 87% (83-91%)87% (83-91%)90% (86-94%) Specificity (95% CI) 74% (62-84%)74% (62-84%)74% (62-84%)Table 1 Performance of the proposed 2017 ACR-EULAR classification criteria for SLEConclusionIn a cohort of SLE patients with NP symptoms, the proposed 2017 ACR-EULAR classification criteria showed similar sensitivity as the 1997 ACR and the SLICC 2012 criteria, but lower specificity. Including ANA negative patients improved sensitivity.References[1] 2018ACR/ARHP Annual Meeting Abstract Supplement. Arthritis Rheumatol, 2018.70Suppl 9: p.1-355.[2] Tedeschi SK, et al., Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration. Arthritis Care Res (Hoboken), 2018. 70(4): p.571-581.[3] Bortoluzzi A, et al., Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford), 2015. 54(5): p.891-8.Disclosure of InterestsRory Monahan: None declared, H.J.L. Beaart: None declared, Maka Gegeneva: None declared, E.G. Brilman: None declared, L.J.J. Beaart- van de Voorde: None declared, César Magro Checa: None declared, Thomas Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Bio...

BackgroundExperimental SLE-models show that complement activation may be a key part of lupus cerebritis and lupus-thrombosis. It is also known that complement factors contribute to the pathology of inflammatory central nervous system (CNS) and neurodegenerative diseasesObjectivesTo analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first CNS neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristicsMethodsPatients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels using ELISA, the activation capacity of complement (CH50 and AP50) using functional assays and different complement components (C1q, C3, C4) using laser nephelometry. Two-hundred healthy controls (HC) were also included for comparisonResultsA total of 280 patients were included. In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared to SLE and HC. This association was specially marked for diffuse NPSLE (SLE: 20.8 versus 8.7; HC: 20,8 versus 7,04; both comparisons P<0.05). No differences in antibody titters were found for C1q CIC when SLE and NPSLE patients where compared. Low C4 was significantly associated with focal NPSLE after using potential predictors, but we lost this association when antiphospholipid antibodies (aPL) were excluded from the model. Low C3, AP50 and CH50 were independently associated with diffuse NPSLE (P<0.001). When SLEDAI-2K was included in the model we did not find any association. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of AP50 and CH50 (P<0.001 for psychosis and P<0.05 or cognitive dysfunction). Furthermore, patients with lupus psychosis showed higher prevalence of low C1q (OR=5, 95% CI 1.5–15.8, P<0.05), low C3 (OR=28.6, 95% CI 3.5–230.4, P<0.001) and low C4 (OR=3.8, 95% CI 1.1–13.3, P<0.05) and cognitive dysfunction showed a higher prevalence of low C1q (OR=5, 95% CI 1.5–15.8, P<0.05), low C3 (OR=4.4, 95% CI 1.8–10.5, P<0.001) and low C4 (OR=3.6, 95% CI 1.5–8.6, P<0.05) when compared with SLE. No significant associations were seen with other individual NPSLE syndromesConclusionsNo association was found between anti-C1q, C1q CIC and NPSLE. The associations between diffuse NPSLE and low C3/AP50 and focal NPSLE and low C4 may be explained by disease activity and th...