Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies. (PRIERR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Limoges
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Direction Générale de la Santé, France
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT01715623
First received: October 22, 2012
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

The investigators previously showed that both antibody class switching (from IgM to IgG, IgA or IgE) and antibody secretion are controlled by a polymorphic "3' regulatory region" (3'RR) of the immunoglobulin heavy chain (IgH) locus. Alleles of the 3'RR have shown influences on the severity and progression of IgA nephropathy (IgAN) (with an over-representation of the B allele among patients with severe kidney IgA deposits). Allele B also constitutes a risk factor for celiac disease, herpetiform dermatitis, psoriasis and rheumatoid arthritis. Since the 3'RR now appears as a crucial regulator of Ig production, we wish to check whether its genetic polymorphism might influence not only the occurrence of immunopathologic processes involving class-switched antibody deregulated production but also the severity of such diseases or the time course of their progression. We wish to focus on two conditions involving class-switched antibodies: on one hand the severe forms of IgE hypersensitivities, and on the other hand a disease involving pathogenic IgA and for which the prognosis is currently very difficult to predict at the onset of the disease: Henoch-Schonlein purpura (HSP).

Regarding hypersensitivities, the diversity of their clinical manifestations prompt us to focus on homogeneous groups of patients and we thus wish to concentrate on two groups of patients who are frequently referred to the hospital: severe allergies to Hymenoptera venoms and severe food allergies related to peanut allergens sensitization. These groups will be built by considering multiple clinical criteria (clinical history, severity of the manifestations, positive skin tests, and positive oral provocation tests for peanut allergens…) and biological criteria authenticating the mechanisms of the disease (high specific serum IgE, demonstration of specific basophil activation by the allergen…).

In parallel to the study in patients, we will include a large cohort of healthy controls (400 individuals), in order to be able to decipher whether correlations can be seen between:

  • IgH 3'RR genotypes
  • The serum accumulation of the various Ig classes, including IgG subclasses, IgA (which are sometimes depicted as protective, sometimes as tolerogenic and anti-inflammatory) and IgE (highly pro-inflammatory and responsible for hypersensitivities)
  • IgG allotypes (with 6 frequent IgG haplotypes known in human and previously reported as correlated with varying levels of IgG and IgE production in normal individuals).

Condition Intervention
Healthy Volunteers
Children With HSP
Subject With Allergy
Lymphoma
Biological: a blood sample

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies.

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • the percentage of allele B [ Time Frame: one day ] [ Designated as safety issue: No ]
    A comparison will be made of the percentage of allele B between healthy volunteers and the three cohorts of subjects with various diseases: (1) lymphoma (lymphoma-proliferation with chromosome 14 translocation ), (2) Henoch-Schonlein purpura HSP (3), allergy (peanut and Hymenoptera venom)


Biospecimen Retention:   Samples Without DNA

We previously showed that both antibody class switching (from IgM to IgG, IgA or IgE) and antibody secretion are controlled by a polymorphic "3' regulatory region" (3'RR) of the immunoglobulin heavy chain (IgH) locus


Estimated Enrollment: 820
Study Start Date: October 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Children with HSP
children with Purpura of Henoch-Schönlein with or without renal complication
Biological: a blood sample
Dosage of Ig
healthy volunteers
healthy volunteers without allergy
Biological: a blood sample
Dosage of Ig
subjects with allergy
subjects with peanut allergy or hymenoptera venom allergy
Biological: a blood sample
Dosage of Ig
lymphoma
lymphoma-proliferation with chromosome 14 translocation
Biological: a blood sample
Dosage of Ig

Detailed Description:

This study should thus finally provide answers to 5 questions which are currently un-addressed:

  • How the 3'RR alleles are linked to IgG allotypes and corresponding IgH haplotypes?
  • Is there a physiological link between 3'RR alleles and production of the various Ig classes and sub-classes?
  • Is the 3'RR polymorphism connected with the risk of more severe forms of allergic diseases?
  • Is the 3'RR polymorphism connected with the risk of occurrence and/or severe evolution of HSP?
  • Is the oncogenicity of translocations affecting the IgH locus connected to the strength of the 3'RR allelic variants?
  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

4 populations :

  • Healthy Volunteers
  • subjects with HPS
  • subjects with peanut allergy or hymenoptera venom allergy
  • lymphoma (biological collection)
Criteria

Inclusion Criteria:

  • Healthy Volunteers:

Age ≥ 18 and < 50 years No history of allergy, haematological malignancies or immune diseases

  • Subjects with allergy:
  • Children:

Age ≥ 4 and < 18 years Clinical history supporting the diagnosis of severe food allergy Peanut specific IgE (Arah2) -Adults: Age > 18 and < 60 years History of severe reaction after antigenic challenge Anaphylactic shock already experienced Specific IgE or positive BAT Positive prick tests

  • subject with HPS:
  • Children:

Age ≥ 4 and < 18 years Henoch Schonlein Purpura (HSP) documented by Ankara 2008 criteria

-Adult: Henoch Schonlein Purpura(HSP) with renal involvement Adults ≥ 18 years,

Exclusion Criteria:

  • subject with allergy or subject with Henoch Schonlein Purpura(HSP): known pregnancy patient under guardianship
  • Healthy Volunteers:

Allergy known pregnancy patient under guardianship

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01715623

Contacts
Contact: Michel COGNE, MD 0555435848 cogne@unilim.fr
Contact: Déborah POSTIL, MD 0555056254 deborah.postil@chu-limoges.fr

Locations
France
Pediatric Recruiting
Limoges, France, 87042
Contact: Vincent GUIGONIS, MD         
Sub-Investigator: Cécile MENETREY, MD         
Principal Investigator: Vincent GUIGONIS, MD         
Clinical Investigation Center Recruiting
Limoges, France, 87042
Contact: Déborah POSTIL, MD         
Principal Investigator: Déborah POSTIL, MD         
Sub-Investigator: Elodie COUVE-DEACON, MD         
Nephrology Recruiting
Limoges, France, 87042
Contact: Jean-Claude Aldigier, MD         
Principal Investigator: Jean-Claude Aldigier, MD         
Pneumology Recruiting
Limoges, France, 87042
Contact: Vincent TOURAINE, MD         
Principal Investigator: Vincent TOURAINE, MD         
Sponsors and Collaborators
University Hospital, Limoges
Institut National de la Santé Et de la Recherche Médicale, France
Direction Générale de la Santé, France
Investigators
Principal Investigator: Michel COGNE, MD Limoges UH
  More Information

No publications provided

Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT01715623     History of Changes
Other Study ID Numbers: I12002 PRIERR
Study First Received: October 22, 2012
Last Updated: July 10, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Limoges:
polymorphism
serum Ig

ClinicalTrials.gov processed this record on September 18, 2014