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

NCT01715623 | Completed

• 1 other identifier: I12002 PRIERR
• Study Type: observational
• Target: 486
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Healthy Volunteers; Children With HSP; Subject With Allergy; Lymphoma

Keywords

polymorphism; serum Ig

Outcome Measures

Primary Outcomes (1)

• the percentage of allele B

  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)

  one day

Study Arms (4)

Children with HSP

children with Purpura of Henoch-Schönlein with or without renal complication

Biological: a blood sample

healthy volunteers

healthy volunteers without allergy

Biological: a blood sample

subjects with allergy

subjects with peanut allergy or hymenoptera venom allergy

Biological: a blood sample

lymphoma

lymphoma-proliferation with chromosome 14 translocation

Biological: a blood sample

Interventions

a blood sample BIOLOGICAL

Dosage of Ig

Children with HSP; healthy volunteers; lymphoma; subjects with allergy

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

4 populations : * Healthy Volunteers * subjects with HPS * subjects with peanut allergy or hymenoptera venom allergy * lymphoma (biological collection)

You may qualify if:

• 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,

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Limoges: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Direction Générale de la Santé, France: collaborator

Study Sites (4)

Clinical Investigation Center

Limoges, 87042, France

Location

Nephrology

Limoges, 87042, France

Location

Pediatric

Limoges, 87042, France

Location

Pneumology

Limoges, 87042, France

Location

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

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michel COGNE, MD

  Limoges UH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 29, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: December 16, 2014
• Last Updated: January 22, 2019

Record last verified: 2019-01

Locations

FR (4)