Study of the Role of Regulator T Cells in the Pathophysiology of Childhood Henoch Schönlein Purpura

Study Overview
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Brief Summary
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The primary objective of this study is to search for evidence of quantitative or functional defects in plasma regulatory T cells (Tregs) in pediatric patients with Henoch Schönlein Purpura (HSP) as compared to a control population.

Detailed Description
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The secondary questions/objectives for this study are: A. During an inflammatory HSP flare, is there a quantitative and / or qualitative defect in plasma Tregs? Are such blood anomalies real or are they due to a modification of the distribution of theses cells to localized sites? B. In the asymptomatic phase, are there quantitative or functional abnormalities among Tregs in subjects with HSP compared to healthy control subjects? C. Are Treg abnormalities associated with modifications in other blood cell lineages, including B cells secreting IgA and abnormally glycosylated IgA1, and secretion of cytokines during acute relapses and during the asymptomatic phase? D. Can streptococcus or other oral or digestive pathogens (bacterial or viral) (as suggested in other chronic diseases such as rheumatoid arthritis ) provoke (via stimulation Th3) isotype commutation towards secretion of IgA1 at the origin of HSP? Does HSP intestinal damage or imbalance of the intestinal microbiota allow the translocation of intestinal microorganisms that sustain this stimulation?

Official Title
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Study of the Role of Regulator T Cells in the Pathophysiology of Childhood Henoch Schönlein Purpura

Conditions
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Henoch Schönlein Purpura

Intervention / Treatment
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* Biological: Blood samples
* Biological: Stool samples


Participation Criteria
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Eligibility Criteria
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General inclusion criteria for all sub-populations included in the study The child (with age- and comprehension-skill-appropriate information) and parents (or persons exercising parental authority) have been informed about the implementation of the study, its objectives, constraints and patient rights The child (depending on age) and parents (or persons exercising parental authority) have given their free and informed consent and signed the consent The patient must be insured or beneficiary of a health insurance plan Inclusion criteria for population A: Henoch Schönlein purpura, acute episodes The diagnosis of Henoch Schönlein purpura was made by a physician according to the EULAR / PRES / PRINTO 2010 criteria (purpura predominantly on the lower limbs associated with one of the following criteria: abdominal pain, arthralgia or arthritis, kidney damage or suggestive histology (immune deposits dominated by Immunoglobulin A (IgA)) The patient is not treated via immunosuppression (steroids or other immunosuppressive / biotherapy) and has not been treated like this for at least 15 days Inclusion criteria for population B: Henoch Schönlein purpura in remission The diagnosis of Henoch Schönlein purpura was made by a physician according to the EULAR / PRES / PRINTO 2010 criteria The patient has has a Henoch Schönlein purpura episode in the past, and no longer has any symptoms of the disease The patient is not treated via immunosuppression (steroids or other immunosuppressive / biotherapy) and has not been treated like this for at least 15 days Inclusion criteria for population C: controls Subjects free from infectious, inflammatory or autoimmune diseases Candidates for elective surgery (circumcision, urological surgery, removal of tonsils and adenoids) Exclusion Criteria: The patient is participating in another interventional study or is in an exclusion period determined by a previous study The child refuses to participate in the study Parents (or persons with parental responsibility if any) refuse to sign the consent It is impossible to correctly inform the patient or his/her parents (or persons with parental authority if any) The patient has another inflammatory or autoimmune disease Patient on immunosuppressive / biotherapy treatments

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HSP: acute episode<br>Patients in this group are going through an acute episode of Henoch Schönlein Purpura. Intervention: Blood samples Intervention: Stool samples | Biological: Blood samples<br>* Compared to routine practice, 3 additional tubes of blood will be drawn for the observational needs of this study.<br>Biological: Stool samples<br>* Stool samples will be collected for the observational needs of this study (and are not part of routine practice).<br>|
| HSP: remission<br>Patients in this group have had Henoch Schönlein Purpura in the past but currently have no symptoms. Intervention: Blood samples Intervention: Stool samples | Biological: Blood samples<br>* Compared to routine practice, 3 additional tubes of blood will be drawn for the observational needs of this study.<br>Biological: Stool samples<br>* Stool samples will be collected for the observational needs of this study (and are not part of routine practice).<br>|
| Control group<br>Control patients recruited from elective surgery candidates at the participating hospitals. Intervention: Blood samples Intervention: Stool samples | Biological: Blood samples<br>* Compared to routine practice, 3 additional tubes of blood will be drawn for the observational needs of this study.<br>Biological: Stool samples<br>* Stool samples will be collected for the observational needs of this study (and are not part of routine practice).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of blood Tregs |  | Day 0 | 
| Absolute Treg count | number / mm^3 | Day 0 | 
| Presence / absence of functional abnormality of plasma Tregs |  | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical abnormalities in other blood cell lines |  | Day 0 | 
| Serum cytokine levels | ng/ml | Day 0 | 
| Serum IgA levels | mg/l | Day 0 | 
| Presence/absence of bacterial translocation |  | Day 0 | 
| Quantification of bacterial translocation | (10^8 copies / µl) | Day 0 | 
| Number of bacterial species detected in the intestinal microbiota |  | Day 0 | 
| Distribution of bacteria taxa present in the intestine among 3 categories | Bacteroidetes, Firmicutes and Actinobacteria | Day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tregs, bacterial translocation, cytokines