Kidney Transplantation
Conditions
Keywords
Chronic AntiBody-Mediated Rejection, ExtraCorporeal Phototherapy, Kidney Transplantation
Brief summary
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.
Interventions
OTHERExtracorporeal phototherapy
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.
Sponsors
University Hospital, Angers
Therakos
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of TFH cells and their activation markers | From the 1st session of ECP to 1 year after the 1st session | Variation in the frequency of TFH cells and their activation markers under treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subsequent ECP response in patients with cABMR | 3 months of treatment per ECP | Study of the 3-month TFH/TFR value of ECP treatment as a marker for subsequent ECP response in patients with cABMR |
| Concentration of pro and anti-inflammatory cytokines | From the 1st session of ECP to 1 year after the 1st session | 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 |
| Concentration of circulating B-cell populations | From the 1st session of ECP to 1 year after the 1st session | Study of the concentration of circulating B-cell populations due to ECP |
| Measurement of genetic markers in TFH cells | At 1 week of the 1st session of ECP and at 3 month after the 1st session | Study of genetic markers in TFH cells in cell co-culture in vitro to describe their function |
| Comparison of clinical data of patients | From the 1st session of ECP to 1 year after the 1st session | Clinical measures (medical examinations) of patients |
| Comparison of biological data of patients | From the 1st session of ECP to 1 year after the 1st session | Biological measures (blood samples) of patients |
Countries
France
Contacts
CONTACTJean-François AUGUSTO, Pr
CONTACTEmma BLANCHET
Outcome results
None listed