GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus

Not Applicable

Completed

• Conditions: Systemic Lupus Erythematosus (SLE)

• Registration Number: NCT01992666
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-11-08
• Study First Submitted QC: 2013-11-18
• Study First Posted: 2013-11-25
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-25
• Last Update Posted: 2018-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 271

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
New genes identification	Once. At inclusion.	Description: Identification of genetic mutations in the following genes: TREX1, SAMHD1, ACP5, DNAse1, DNAse1L3, or in new lupus genes.

Secondary Outcome Measures

Name	Time	Method
Immunological genotype and clinical abnormalities correlation	Once. At inclusion	Correlate genotype to immunological (interferon alpha, ...) and clinical abnormalities (microcrania, growth retardation, ...)

Trial Locations

Locations (26)

Service d'hématologie / oncologie pédiatrique - CHU; 🇫🇷 Angers, France

Néphrologie Pédiatrique - CHU Besançon; 🇫🇷 Besançon, France

Hôpital Femme Mère Enfant; 🇫🇷 Bron, France

Service de Néphrologie Pédiatrique; 🇫🇷 Clermont Ferrand, France

Service de pédiatrie - CHU Fort de France; 🇫🇷 Fort De France, France

Service de Néphrologie et Rhumatologie Pédiatrique; 🇫🇷 Grenoble, France

Service de Rhumatologie Pédiatrique - Hôpital de Bicêtre; 🇫🇷 Le Kremlin Bicêtre, France

Service de médecine interne - Centre de référence des maladies rares; 🇫🇷 Lille, France

Service de néphrologie, endocrinologie, maladie métabolique et hématologie bénigne pédiatriques - Hôpital Jeanne de Flandre; 🇫🇷 Lille, France

édiatrie générale, urgences et maladies infectieuses, Hôpital Salengro; 🇫🇷 Lille, France

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