THU0353 Serum Tweak Levels in Patients with Neuropsychiatric Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is autoimmune disease involving various organs including the nervous system. Neuropsychiatric SLE (NPSLE) occurs in 30 - 40% of SLE patients. One of the most common manifestations of NPSLE is cognitive dysfunction (CD) which occurs in 21 - 81% of SLE patients. TWEAK is a TNF family ligand that mediates pleotropic effects through its receptor Fn14, including the stimulation of inflammatory cytokine production and induction of neuronal death. Recent studies in animal models and human SLE patients suggest TWEAK as a potential mediator of NPSLE. Objectives To examine potential association between serum TWEAK levels and NPSLE, mainly cognitive dysfunction in patients with SLE, to determine a possible association with other types of organ involvement and specific autoantibodies (antineuronal, antiphospholipid, anti-dsDNA, antinuclear, anti-P protein, etc), and a correlation with disease activity. Methods The SLE patients (fulfilling ACR classification criteria for SLE) have undergone a complete neuropsychiatric examination for the presence NPSLE including brain MRI. CD has been assessed according to the ACR classification of NPSLE. The activity of the disease was evaluated using the diseases activity index (SLEDAI). Serum TWEAK levels were measured by ELISA. Results We analyzed 90 SLE patients. The neuropsychiatric involvement and cognitive dysfunction with moderate to severe disability was diagnosed in 58 (64.4%), 53 (58.8%) patients, resp. The headache, cranial neuropathy and epilepsy were the most frequent neurological manifestations. Active disease was present in 44 patients (48.8%). In contrast to recent studies no significant differences were found in the serum TWEAK levels between patients with and without NPSLE. There were also no differences in serum TWEK levels between patients with and without CD. We did not observe any association of serum TWEAK levels with different organ SLE manifestations, presence of antibodies or disease activity. Conclusions NPSLE and CD were found to be frequent SLE manifestations in our cohort. However, serum TWEAK levels do not seem to be a reliable biomarker for NPSLE or other manifestations in patients with SLE. Further studies in patients with new NPSLE manifestation prior to initiating therapy may be needed. References Wen J, Xia Y, Stock A et al. Neuropsychiatric disease in murine lupus is dependent on the TWEAK/Fn14 pathway. J Autoimmun 2013; 43: 44–54. Stock AD, Wen J, Putterman Ch. Neuropsychiatric lupus, the blood brain barrier, and the TWEAK/Fn14 pathway. Front Immunol 2013; 4: 484. Fragoso-Loyo H, Atisha-Fregoso Y, Nunez-Alvarez CA et al. Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erythematosus. Lupus 2015 Oct 13.[Epub ahead of print] Xu WD, Zhao Y, Liu Y. Role of the TWEAK/Fn14 pathway in autoimmune diseases. Immunol Res. 2015 Dec 12 [Epub ahead of print] Acknowledgement Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology). Disclosure of Interest None declared