GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus (GENIAL)

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease for which the aetiology includes genet-ic and environmental factors. It is rare in children as compared to adults. The severity may be related to greater involvement of genetic factors in children. The impact of genetics in the development of SLE is important, and the risk of recurrence in siblings evaluated by lambda S ratio is 30 in SLE, while it is 15 for type-1 diabetes and 8 rheumatoid arthritis, thereby indicating high impact of genetics in SLE. Recently, the group of Professor Yanick Crow in Manchester and other teams has identified new forms of lupus Mendelian genetics. The TREX1 and genes involved in the SAMHD1 frostbite lupus. Nearly 2 % of all adult subjects with SLE have a heterozygous mutation in the TREX1 gene, which therefore represents the first genetic cause of SLE. The team of Professor Crow also identified the ACP5 gene that is responsible for SLE associated with Spondylo-epiphyseal enchondro-epiphyseal dysplasia (syndromic lupus). Other groups have identified mutations in two genes encoding a DNAse (DNAse1 and DNAse1L3) responsible for familial monogenic forms of SLE. These new genes SLE were identified through research of germ-line mutations in cases of lupus syndromic or family. In collaboration with Professor Crow, we are currently undergoing characterization of a novel gene of SLE in a family and we have identified a second locus identified in another family. The identification of these genes provides a better understanding of the mechanisms regulating immune tolerance in humans. The frequency of these genetic forms is not known. There is very little data on the immunological phenotype of these patients. This is a clinical study to investigate the genetic and immunological abnormalities associated with pediatric SLE. The aim are to: study the genetics of pediatric SLE (or syndromic or family) and to search for mutations in the known genetic lupus or new genes in collaboration with Professor Yanick Crow. study the lymphocyte subpopulations and serum cytokines in pediatric patients with SLE (or syndromic or family) in the large Rhône- Alpes- Auvergne area.

Description: Identification of genetic mutations in the following genes: TREX1, SAMHD1, ACP5, DNAse1, DNAse1L3, or in new lupus genes.

Correlate genotype to immunological (interferon alpha, …) and clinical abnormalities (microcrania, growth retardation, …)

Identification of specific immunological factors of pediatric patients with SLE (or syndromic or family)

Characterization of sub-groups: size, articular manifestations (SLEDAI), hematology (hemoglobin, platelets, G White, ANA, ds-DNA, C3, C4, CH50, creatinine, proteinuria.

Inclusion Criteria: Male or female subject, major or minor of any age with SLE (defined according to the ACR criteria) Onset pediatric (<18 years) OR Syndromic Lupus (associated with growth retardation, neurological deficit not related to lupus, frostbite, lymphoproliferation, the kidney malformations, heart, lung, brain calcifications) OR Lupus in context with familial consanguinity OR Familial cases (2 cases of SLE related first degree relative) OR related topic of the first degree to a lupus patient participant (if family lupus or related parents) OR mother/father's lupus patient (in cas of simplex lupus) A person or beneficiary entitled to a social security scheme or similar Informed consent signed by the person (or parent / holding parental authority for minors) Exclusion Criteria: - none

Service de néphrologie, endocrinologie, maladie métabolique et hématologie bénigne pédiatriques - Hôpital Jeanne de Flandre

Service d'immunologie et rhumatologie pédiatrique - Centre de référence de maladies rhumatologiques et inflammatoires rares en pédiatrie-Hôpital Necker-Enfants malades

Weill O, Decramer S, Malcus C, Kassai B, Rouvet I, Ginhoux T, Crow YJ, Rieux-Laucat F, Soulas-Sprauel P, Pagnier A, Kone-Paut I, Piram M, Galeotti C, Samaille C, Reumaux H, Lanteri A, Dubois SM, Lefebvre H, Burtey S, Maurier F, Carbasse A, Lemelle I, Meinzer U, Despert V, Flodrops H, Fabien N, Ranchin B, Hachulla E, Bader-Meunier B, Belot A. Familial and syndromic lupus share the same phenotype as other early-onset forms of lupus. Joint Bone Spine. 2017 Oct;84(5):589-593. doi: 10.1016/j.jbspin.2016.12.008. Epub 2016 Dec 28.