Ignite Creation Date:
2024-05-06 @ 1:03 AM
Last Modification Date:
2024-10-26 @ 10:58 AM
Study NCT ID:
NCT01715623
Status:
COMPLETED
Last Update Posted:
2019-01-22
First Post:
2012-10-22
Brief Title:
Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies
Sponsor:
University Hospital Limoges
Organization:
University Hospital Limoges
Study Overview
Official Title:
Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies
Status:
COMPLETED
Status Verified Date:
2019-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRIERR
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 3RR of the immunoglobulin heavy chain IgH locus Alleles of the 3RR 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 3RR 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 3RR 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
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 3RR 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
Detailed Description:
This study should thus finally provide answers to 5 questions which are currently un-addressed
How the 3RR alleles are linked to IgG allotypes and corresponding IgH haplotypes
Is there a physiological link between 3RR alleles and production of the various Ig classes and sub-classes
Is the 3RR polymorphism connected with the risk of more severe forms of allergic diseases
Is the 3RR polymorphism connected with the risk of occurrence andor severe evolution of HSP
Is the oncogenicity of translocations affecting the IgH locus connected to the strength of the 3RR allelic variants
How the 3RR alleles are linked to IgG allotypes and corresponding IgH haplotypes
Is there a physiological link between 3RR alleles and production of the various Ig classes and sub-classes
Is the 3RR polymorphism connected with the risk of more severe forms of allergic diseases
Is the 3RR polymorphism connected with the risk of occurrence andor severe evolution of HSP
Is the oncogenicity of translocations affecting the IgH locus connected to the strength of the 3RR allelic variants
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None