GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) Clinical Trial

— GENIAL  

Official title:

GENetic & Immunologic Abnomalies in Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01992666
• Other study ID #: 2012.769
• Secondary ID: 2012-A01449-34
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Est. completion date: October 2016

Study information

• Verified date: July 2018
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 271
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

Genetic:
• Blood sampling
Immunologic and genetic analysis from a single blood sample.

Locations

Country	Name	City	State
France	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	édiatrie générale, urgences et maladies infectieuses, Hôpital Salengro	Lille
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	Service de Néphrologie - Hôpital Edouard Herriot	Lyon
France	Centre de néphrologie et de transplantation rénale - Hôpital de la conception	Marseille
France	Service de médecine infantile- Hôpital Nord	Marseille
France	Service de médecine interne - Hôpitaux privés de Metz	Metz
France	ervice d'urgence et post-urgences pédiatriques - CHU Arnaud de Villeneuve	Montpellier
France	Service médecine infantile 2	Nancy
France	Service de néphrologie pédiatrique - CHU de Nantes	Nantes
France	Service d'immunologie et rhumatologie pédiatrique - Centre de référence de maladies rhumatologiques et inflammatoires rares en pédiatrie-Hôpital Necker-Enfants malades	Paris
France	Service de médecine interne - Hôpital Saint Antoine	Paris
France	Service de pédiatrie générale - Hôpital Robert-Debré	Paris
France	Médecine Interne Adulte - Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Service de Rhumatologie - Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Service pédiatrie grands enfants-adolescents - CHU Hôpital Sud	Rennes
France	Hôpital Nord	Saint Etienne
France	Service de Pédiatrie Générale - CHU Réunion	Saint Pierre
France	Service de néphrologie - médecine interne - Hypertension pédiatrique - Hôpital des enfants	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunological component	Identification of specific immunological factors of pediatric patients with SLE (or syndromic or family)	Once. At inclusion
Other	Characterization of sub-groups: size, articular manifestations (SLEDAI), hematology (hemoglobin, platelets, G White, ANA, ds-DNA, C3, C4, CH50, creatinine, proteinuria.		Once. At inclusion
Primary	New genes identification	Description: Identification of genetic mutations in the following genes: TREX1, SAMHD1, ACP5, DNAse1, DNAse1L3, or in new lupus genes.	Once. At inclusion.
Secondary	Immunological genotype and clinical abnormalities correlation	Correlate genotype to immunological (interferon alpha, …) and clinical abnormalities (microcrania, growth retardation, …)	Once. At inclusion