OP0257 CHILDHOOD-ONSET MONOGENIC SYSTEMIC LUPUS ERYTHEMATOSUS NOT DUE TO COMPLEMENT DEFICIENCY: ASYSTEMATIC REVIEW OF 90 CASES
Authors: Natalia Cabrera, Pauline Nakhleh, Jean-Christophe Lega, Alexandre Belot
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The paediatric SLE (pSLE) are estimated 10 to 17% of SLE (1). Studies comparing pSLE with adult-onset SLE reported high prevalence of pre-existing organ damage at diagnosis due to the diagnosis delay, more severe disease clinical course with high disease activity resulting in worse prognosis in pSLE (1,2). Recently, whole exome sequencing and next-gene sequencing have facilitated the identification of rare monogenic variants associated with SLE and lupus-like phenotypes with high penetrance (3,4) <h3>Objectives:</h3> To reporting the whole spectrum of monogenic pSLE according to pathway abnormalities, using a meta-analysis (MA) approach. <h3>Methods:</h3> A systematic review of studies focused on monogenic pSLE were analysed. To be included in the systematic review, studies had to meet simultaneously all the following criteria: (i) reported at least 1 case of SLE (ii) started before the age of 16 (iii) with clearly description of the diagnosis criteria and (iv) provided genetic data of the case. We pooled the genes into three main groups of signalling pathways: (i) genes that affect adaptive immunity pathways including the lymphocyte apoptosis (FAS, KRAS, PTPN11, SHOC2) and the B and T cell development checkpoints (PRKCD, RAG2, IKZF1,DOCK8, WASP), (ii) genes containing type I interferon (IFN) pathways (ACP5, TREX1, SAMHD1, RNASEH2A, RNASEH2B, RNASEH2C, IFIH1, DNASE1L3, DNASE1, TMEM173, Tetrasomy 9), and (iii) metabolism pathways including both amino acid metabolism (PEPD, SLC7A7, MAN2B1) and oxidative metabolism (NCF2). Clinical and laboratory data were analysed according to the SLICC classification. <h3>Results:</h3> We included 42 articles encompassing 88 patients, plus 2 additional unpublished cases of one author (AB). The MA process were carried out according to the PRISMA statement. According to the SLICC classification, the blood disorders were significantly higher in the group of the metabolism pathway as well as the positivity of direct Coombs test. The positivity of antibodies anti-Sm was also a distinguishing element for this group, while the positivity of ALP antibodies was the lonely manifestation to distinguish the adaptive immunity pathway from the others. Fever, recurrent infections, hepatosplenomegaly, and pulmonary diseases were significantly predominant in the metabolism pathways. In the group of the IFN pathway, the most distinctive criteria were the neurological manifestations and bone changes. There were no statistically significant differences in all groups concerning all other clinical or immunological criteria. <h3>Conclusion:</h3> This is the first quantitative analysis of multiples cases reports, comparing the whole spectrum of monogenic pSLE according to three different pathways. Our results suggest that abnormalities in signaling pathway delimitate different SLE juvenile subset. The clinical and biological differing between the three signaling pathway were not specific, but our results may help to detect phenotypes requiring targeted genetic investigations. Subsets of SLE syndrome have to be identified to drive the treatment and propose personalized medicine. <h3>References:</h3> [1] Livingston B, Bonner A, Pope J. Differences in clinical manifestations between childhood-onset lupus and adult-onset lupus: a meta-analysis. Lupus. 2011 Nov;20(13):1345–55. [2] Hedrich CM, Smith EMD, Beresford MW. Juvenile-onset systemic lupus erythematosus (jSLE) – Pathophysiological concepts and treatment options. Best Pract Res Clin Rheumatol. 2017 Aug;31(4):488–504. [3] Tsokos GC, Lo MS, Reis PC, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016 Dec;12(12):716–30. [4] Chung SA, Shum AK. Rare variants, autoimmune disease, and arthritis: Curr Opin Rheumatol. 2016 Jul;28(4):346–51. <h3>Disclosure of Interests:</h3> None declared