Clinical trial NCT01992666: GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus
Official title: GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Systemic lupus erythematosus
genetic
immunological
pediatric
mutation
lupus
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2013-11-25
Enrollment: 271
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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)
2. A person or beneficiary entitled to a social security scheme or similar
3. Informed consent signed by the person (or parent / holding parental authority for minors)

Exclusion Criteria:

- none

Primary outcomes:
measure: New genes identification
timeFrame: Once. At inclusion.
Secondary outcomes:
measure: Immunological genotype and clinical abnormalities correlation
timeFrame: Once. At inclusion
Other outcomes:
measure: Immunological component
timeFrame: Once. At inclusion
measure: Characterization of sub-groups: size, articular manifestations (SLEDAI), hematology (hemoglobin, platelets, G White, ANA, ds-DNA, C3, C4, CH50, creatinine, proteinuria.
timeFrame: Once. At inclusion
Locations:
city: Angers
country: France
facility: Service d'hématologie / oncologie pédiatrique - CHU
city: Besançon
country: France
facility: Néphrologie Pédiatrique - CHU Besançon
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Clermont Ferrand
country: France
facility: Service de Néphrologie Pédiatrique
city: Fort De France
country: France
facility: Service de pédiatrie - CHU Fort de France
city: Grenoble
country: France
facility: Service de Néphrologie et Rhumatologie Pédiatrique
city: Le Kremlin Bicêtre
country: France
facility: Service de Rhumatologie Pédiatrique - Hôpital de Bicêtre
city: Lille
country: France
facility: Service de médecine interne - Centre de référence des maladies rares
city: Lille
country: France
facility: Service de néphrologie, endocrinologie, maladie métabolique et hématologie bénigne pédiatriques - Hôpital Jeanne de Flandre
city: Lille
country: France
facility: édiatrie générale, urgences et maladies infectieuses, Hôpital Salengro
city: Lyon
country: France
facility: Service de Néphrologie - Hôpital Edouard Herriot
city: Marseille
country: France
facility: Centre de néphrologie et de transplantation rénale - Hôpital de la conception
city: Marseille
country: France
facility: Service de médecine infantile- Hôpital Nord
city: Metz
country: France
facility: Service de médecine interne - Hôpitaux privés de Metz
city: Montpellier
country: France
facility: ervice d'urgence et post-urgences pédiatriques - CHU Arnaud de Villeneuve
city: Nancy
country: France
facility: Service médecine infantile 2
city: Nantes
country: France
facility: Service de néphrologie pédiatrique - CHU de Nantes
city: Paris
country: France
facility: Service d'immunologie et rhumatologie pédiatrique - Centre de référence de maladies rhumatologiques et inflammatoires rares en pédiatrie-Hôpital Necker-Enfants malades
city: Paris
country: France
facility: Service de médecine interne - Hôpital Saint Antoine
city: Paris
country: France
facility: Service de pédiatrie générale - Hôpital Robert-Debré
city: Pierre-Bénite
country: France
facility: Médecine Interne Adulte - Centre Hospitalier Lyon Sud
city: Pierre-Bénite
country: France
facility: Service de Rhumatologie - Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: Service pédiatrie grands enfants-adolescents - CHU Hôpital Sud
city: Saint Etienne
country: France
facility: Hôpital Nord
city: Saint Pierre
country: France
facility: Service de Pédiatrie Générale - CHU Réunion
city: Toulouse
country: France
facility: Service de néphrologie - médecine interne - Hypertension pédiatrique - Hôpital des enfants
Study officials:
affiliation: Hospices Civils de Lyon
name: Alexandre Belot, Dr
role: STUDY_DIRECTOR
References:
citation: 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.