<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01715623</url>
  </required_header>
  <id_info>
    <org_study_id>I12002 PRIERR</org_study_id>
    <nct_id>NCT01715623</nct_id>
  </id_info>
  <brief_title>Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies.</brief_title>
  <acronym>PRIERR</acronym>
  <official_title>Polymorphism of the IgH Locus Regulatory Region as a Prognostic Factor During Immune Pathologies.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Limoges</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Direction Générale de la Santé, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Limoges</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators previously showed that both antibody class switching (from IgM to IgG, IgA&#xD;
      or IgE) and antibody secretion are controlled by a polymorphic &quot;3' regulatory region&quot; (3'RR)&#xD;
      of the immunoglobulin heavy chain (IgH) locus. Alleles of the 3'RR have shown influences on&#xD;
      the severity and progression of IgA nephropathy (IgAN) (with an over-representation of the B&#xD;
      allele among patients with severe kidney IgA deposits). Allele B also constitutes a risk&#xD;
      factor for celiac disease, herpetiform dermatitis, psoriasis and rheumatoid arthritis. Since&#xD;
      the 3'RR now appears as a crucial regulator of Ig production, we wish to check whether its&#xD;
      genetic polymorphism might influence not only the occurrence of immunopathologic processes&#xD;
      involving class-switched antibody deregulated production but also the severity of such&#xD;
      diseases or the time course of their progression. We wish to focus on two conditions&#xD;
      involving class-switched antibodies: on one hand the severe forms of IgE hypersensitivities,&#xD;
      and on the other hand a disease involving pathogenic IgA and for which the prognosis is&#xD;
      currently very difficult to predict at the onset of the disease: Henoch-Schonlein purpura&#xD;
      (HSP).&#xD;
&#xD;
      Regarding hypersensitivities, the diversity of their clinical manifestations prompt us to&#xD;
      focus on homogeneous groups of patients and we thus wish to concentrate on two groups of&#xD;
      patients who are frequently referred to the hospital: severe allergies to Hymenoptera venoms&#xD;
      and severe food allergies related to peanut allergens sensitization. These groups will be&#xD;
      built by considering multiple clinical criteria (clinical history, severity of the&#xD;
      manifestations, positive skin tests, and positive oral provocation tests for peanut&#xD;
      allergens…) and biological criteria authenticating the mechanisms of the disease (high&#xD;
      specific serum IgE, demonstration of specific basophil activation by the allergen…).&#xD;
&#xD;
      In parallel to the study in patients, we will include a large cohort of healthy controls (400&#xD;
      individuals), in order to be able to decipher whether correlations can be seen between:&#xD;
&#xD;
        -  IgH 3'RR genotypes&#xD;
&#xD;
        -  The serum accumulation of the various Ig classes, including IgG subclasses, IgA (which&#xD;
           are sometimes depicted as protective, sometimes as tolerogenic and anti-inflammatory)&#xD;
           and IgE (highly pro-inflammatory and responsible for hypersensitivities)&#xD;
&#xD;
        -  IgG allotypes (with 6 frequent IgG haplotypes known in human and previously reported as&#xD;
           correlated with varying levels of IgG and IgE production in normal individuals).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study should thus finally provide answers to 5 questions which are currently&#xD;
      un-addressed:&#xD;
&#xD;
        -  How the 3'RR alleles are linked to IgG allotypes and corresponding IgH haplotypes?&#xD;
&#xD;
        -  Is there a physiological link between 3'RR alleles and production of the various Ig&#xD;
           classes and sub-classes?&#xD;
&#xD;
        -  Is the 3'RR polymorphism connected with the risk of more severe forms of allergic&#xD;
           diseases?&#xD;
&#xD;
        -  Is the 3'RR polymorphism connected with the risk of occurrence and/or severe evolution&#xD;
           of HSP?&#xD;
&#xD;
        -  Is the oncogenicity of translocations affecting the IgH locus connected to the strength&#xD;
           of the 3'RR allelic variants?&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 16, 2014</completion_date>
  <primary_completion_date type="Actual">April 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>the percentage of allele B</measure>
    <time_frame>one day</time_frame>
    <description>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)</description>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">486</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Children With HSP</condition>
  <condition>Subject With Allergy</condition>
  <condition>Lymphoma</condition>
  <arm_group>
    <arm_group_label>Children with HSP</arm_group_label>
    <description>children with Purpura of Henoch-Schönlein with or without renal complication</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy volunteers</arm_group_label>
    <description>healthy volunteers without allergy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>subjects with allergy</arm_group_label>
    <description>subjects with peanut allergy or hymenoptera venom allergy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>lymphoma</arm_group_label>
    <description>lymphoma-proliferation with chromosome 14 translocation</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>a blood sample</intervention_name>
    <description>Dosage of Ig</description>
    <arm_group_label>Children with HSP</arm_group_label>
    <arm_group_label>healthy volunteers</arm_group_label>
    <arm_group_label>lymphoma</arm_group_label>
    <arm_group_label>subjects with allergy</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      We previously showed that both antibody class switching (from IgM to IgG, IgA or IgE) and&#xD;
      antibody secretion are controlled by a polymorphic &quot;3' regulatory region&quot; (3'RR) of the&#xD;
      immunoglobulin heavy chain (IgH) locus&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        4 populations :&#xD;
&#xD;
          -  Healthy Volunteers&#xD;
&#xD;
          -  subjects with HPS&#xD;
&#xD;
          -  subjects with peanut allergy or hymenoptera venom allergy&#xD;
&#xD;
          -  lymphoma (biological collection)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy Volunteers:&#xD;
&#xD;
        Age ≥ 18 and &lt; 50 years No history of allergy, haematological malignancies or immune&#xD;
        diseases&#xD;
&#xD;
          -  Subjects with allergy:&#xD;
&#xD;
          -  Children:&#xD;
&#xD;
        Age ≥ 4 and &lt; 18 years Clinical history supporting the diagnosis of severe food allergy&#xD;
        Peanut specific IgE (Arah2) -Adults: Age &gt; 18 and &lt; 60 years History of severe reaction&#xD;
        after antigenic challenge Anaphylactic shock already experienced Specific IgE or positive&#xD;
        BAT Positive prick tests&#xD;
&#xD;
          -  subject with HPS:&#xD;
&#xD;
          -  Children:&#xD;
&#xD;
        Age ≥ 4 and &lt; 18 years Henoch Schonlein Purpura (HSP) documented by Ankara 2008 criteria&#xD;
&#xD;
        -Adult: Henoch Schonlein Purpura(HSP) with renal involvement Adults ≥ 18 years,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  subject with allergy or subject with Henoch Schonlein Purpura(HSP): known pregnancy&#xD;
             patient under guardianship&#xD;
&#xD;
          -  Healthy Volunteers:&#xD;
&#xD;
        Allergy known pregnancy patient under guardianship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michel COGNE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Limoges UH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Investigation Center</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nephrology</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pediatric</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pneumology</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>polymorphism</keyword>
  <keyword>serum Ig</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01715623
org study id: I12002 PRIERR
nct id: NCT01715623
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
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).
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?
observational model: Cohort
time perspective: Prospective
measure: the percentage of allele B
time frame: one day
description: 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)
arm group label: Children with HSP
description: children with Purpura of Henoch-Schönlein with or without renal complication
arm group label: healthy volunteers
description: healthy volunteers without allergy
arm group label: subjects with allergy
description: subjects with peanut allergy or hymenoptera venom allergy
arm group label: lymphoma
description: lymphoma-proliferation with chromosome 14 translocation
intervention type: Biological
intervention name: a blood sample
description: Dosage of Ig
arm group label: Children with HSP
arm group label: healthy volunteers
arm group label: lymphoma
arm group label: subjects with allergy
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
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 4 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Michel COGNE, MD
role: Principal Investigator
affiliation: Limoges UH
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor