OP0217 A permeable blood-brain barrier is not required for neuropsychatric manifestations in sle and pss. (12th June 2018)

• Record Type: Journal Article
• Authors: Lauvsnes, M.B.; Tjensvoll, A.B.; Maroni, S.S.; Kvivik, I.; Grimstad, T.B.; Greve, O.J.; Harboe, E.; Gøransson, L.G.; Putterman, C.; Omdal, R.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 157
• Page End: 158
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.3923
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: A prevailing hypothesis for neuropsychiatric (NP) manifestations in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) is that brain reactive autoantibodies can enter the brain through an impaired blood-brain barrier (BBB) during inflammatory conditions. Based on murine models the cytokine TWEAK could contribute to NP phenomena by binding Fn14 on brain endothelial cells. This will open the BBB and allow brain-reactive autoantibodies produced in the periphery to reach their targets in the brain. Objectives: The aim of this study was to investigate the role of the BBB's permeability for NP manifestations in human SLE and pSS. Also, we wished to investigate whether increased TWEAK concentrations could be attributed to brain involvement as previously documented in the animal models of SLE. We compared TWEAK with markers of BBB permeability and astrocyte activation. Also, we estimated intrathecal B-cell activation, anti-NR2 abs, and explored whether these variables were associated with NP manifestations. Methods: In a population-based cohort of 50 SLE (all fulfilling the ACR criteria) and 52 pSS patients (all fulfilling the AECG criteria) NP manifestations were classified according to the ACR recommendations for NP-SLE. TWEAK, anti-NR2 antibodies (abs) were measured in serum and cerebrospinal fluid (CSF), S100b in CSF, and IgG index and Q-albumin were calculated. Results: TWEAK concentrations in serum/CSF, as well as S100B and anti-NR2 abs in CSF, Q-albumin and IgG indices are shown in table 1. Associations between intrathecal TWEAK and S100B, Q-albumin and IgG index are given in table 2. No associations were found between TWEAK in serum/CSF and NP manifestations in the SLE, nor in the pSS group. Further, no associations were revealed between NP manifestations and S100B, Q-albumin or IgG index. Anti-NR2 abs in CSF were associated with increased OR for dysfunction in the cognitive domains visuospatial processing (OR 4.9, p=0.03) and motor functioning (OR 6.0, p=0.006) when corrected for age, gender, disease duration and education. Conclusions: Although several studies show that TWEAK seems necessary for CNS involvement in murine SLE, no clinical NP manifestations could be attributed to TWEAK concentrations in CSF/serum in the SLE- or pSS patients. Further, no associations were found between NP manifestations and the integrity of the BBB (Q-albumin), nor astrocyte activation. The TWEAK concentration was higher in CSF than blood in both the SLE- and pSS patients, indicating an intrathecal production. TWEAK in CSF covaried with S100B in CSF possibly reflecting a common ongoing intracerebral process. We hypothesise that TWEAK is neuroprotective in human SLE and pSS. Brain residing immune cells produce brain reactive abs, for example anti-NR2 abs. These abs bind to neurons, and the cellular stress induced in the neurons leads to production of TWEAK. Concurrently, the activated B cells secret proinflammatory cytokines that among other actions activate astrocytes that in turn produce S100B, also a neuroprotective protein. Disclosure of Interest: None declared