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.
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
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
Single group
Extracorporeal phototherapy
Other interventionThe 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.
Frequency of TFH cells and their activation markers
Variation in the frequency of TFH cells and their activation markers under treatment.
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
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
Concentration of circulating B-cell populations
Study of the concentration of circulating B-cell populations due to ECP
Measurement of genetic markers in TFH cells
Study of genetic markers in TFH cells in cell co-culture in vitro to describe their function
Click on the lead sponsor to view all of their trials.
University Hospital, Angers
Lead sponsor
Therakos
Collaborator
