Impact of ExtraCorporeal Phototherapy (ECP) on Auxiliary Follicular T-lymphocytes and Circulating B-lymphocytes During Chronic AntiBody-Mediated Rejection in Kidney Transplantation.

Study Overview
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Brief Summary
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Chronic AntiBody-Mediated Rejection (cABMR) is the leading cause of late kidney transplant loss (after 1 year of kidney transplantation). Its therapeutic management is poorly codified and there is currently no treatment referring. Extracorporeal phototherapy (ECP) is a therapeutic apheresis that involves purifying mononucleated cells in the blood, exposing them to UltraViolet A (UVA) and re-injecting them to the patient. This treatment is used as common care in the first line as part of the treatment of cutaneous T lymphoma and in the second line as part of the graft versus host reaction after bone marrow allograft. The mechanisms underlying the action of the ECP are not well known. They are mediated by the reinjection of cells exposed to UVA which enter apoptosis and induce immunomodulation. Recent work during cABMR shows that TFH lymphocytes, the maturing population of B lymphocytes, are deregulated and activated. The hypothesis is that ECP can modulate T Follicular Helper (TFH) lymphocytes during cABMR.

Official Title
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Impact of ExtraCorporeal Phototherapy (ECP) on Auxiliary Follicular T-lymphocytes and Circulating B-lymphocytes During Chronic AntiBody-Mediated Rejection in Kidney Transplantation: IPECAM

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: Extracorporeal phototherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECP treatment decision based on transplant team habits (care management) Age ≥ 18 years Affiliation to a French social security scheme Kidney transplant at least 6 months prior to inclusion cABMR proven by a renal graft biopsy less than 3 months and meeting the following histological criteria: allograft glomerulopathy (cg>0, and maximum score cg2) or intimal fibrosis C4d positive or ptc+g greater than or equal to 2 Presence of Donor Specific Antibody (DSA) Interstitial Fibrosis and Tubular Atrophy (IFTA) less than or equal to 2 Glomerular filtration rate > 30 mL/min/1.73 m2 Signed informed consent to participate in the study Exclusion Criteria: Active infection or infection with hepatitis B, C or HIV virus Pregnant, breastfeeding or parturient woman Person deprived of liberty by judicial or administrative decision Person receiving psychiatric care under duress Person subject to legal protection Person out of state to express consent

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Extracorporeal phototherapy<br> | Other: Extracorporeal phototherapy<br>* The principle of ECP is to collect mononucleated cells from the blood by centrifugation. After purification, the mononucleated cells are incubated ex-vivo with a photo-activatable DNA intercalating agent (8-methoxypsoralen, UVADEX®), then re-injected to the patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of TFH cells and their activation markers | Variation in the frequency of TFH cells and their activation markers under treatment. | From the 1st session of ECP to 1 year after the 1st session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subsequent ECP response in patients with cABMR | Study of the 3-month TFH/TFR value of ECP treatment as a marker for subsequent ECP response in patients with cABMR | 3 months of treatment per ECP | 
| Concentration of pro and anti-inflammatory cytokines | Study of the concentration of pro-inflammatory cytokines (IL-6, TNFα, IL-1β, IL-17, IFN-gamma, IL-21, IL-12, IL-17, CXCL13) and anti-inflammatory cytokines (IL10, TGF-b) over time in ECP | From the 1st session of ECP to 1 year after the 1st session | 
| Concentration of circulating B-cell populations | Study of the concentration of circulating B-cell populations due to ECP | From the 1st session of ECP to 1 year after the 1st session | 
| Measurement of genetic markers in TFH cells | Study of genetic markers in TFH cells in cell co-culture in vitro to describe their function | At 1 week of the 1st session of ECP and at 3 month after the 1st session | 
| Comparison of clinical data of patients | Clinical measures (medical examinations) of patients | From the 1st session of ECP to 1 year after the 1st session | 
| Comparison of biological data of patients | Biological measures (blood samples) of patients | From the 1st session of ECP to 1 year after the 1st session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic AntiBody-Mediated Rejection, ExtraCorporeal Phototherapy, Kidney Transplantation