Clinical and immunological follow-up of very long-term kidney transplant recipients treated with calcineurin inhibitors indicates dual phenotypes

• DOI: 10.1016/j.kint.2020.09.036
• Publication Date: 2020-11-01T14:38:05Z
• Authors: Amaury Dujardin; Mélanie Chesneau; Florian Dubois; Richard Danger; Linh Bui; Clarisse Kerleau; Pierrick Guérif; Sophie Brouard; Jacques Dantal
• Keywords: Graft Rejection; MESH: Graft Survival; phenotype; MESH: Transplant Recipients; [SDV]Life Sciences [q-bio]; Calcineurin Inhibitors; 610; kidney transplantation; MESH: Graft Rejection; MESH: Phenotype; MESH: Kidney Transplantation; 03 medical and health sciences; 0302 clinical medicine; 617; Humans; B cell; MESH: Humans; tolerance; Graft Survival; MESH: Follow-Up Studies; Kidney Transplantation; Transplant Recipients; 3. Good health; [SDV] Life Sciences [q-bio]; Phenotype; MESH: Calcineurin Inhibitors; MESH: Immunosuppressive Agents; rejection; Immunosuppressive Agents; Follow-Up Studies

Operationally tolerant kidney transplant recipients harbor an immunological signature, associated with low rejection risk, and focused on B lymphocytes. Here, we investigated whether patients with long-term transplantation and still on immunosuppressive therapy would present such a signature of low immunological rejection risk, compared to more recently transplanted patients. Of 114 kidney transplant recipients enrolled, 38 with more than 25 years of graft survival and stable graft function under calcineurin inhibitors, were matched with two different groups of transplanted patients (10-15 and 5-7 years after transplantation). Three phenotypes associated with low immunological rejection risk (Tfh, B and regulatory T cells), initially found in operationally tolerant kidney transplant recipients, and the composite score of tolerance (combination of six transcriptomic markers, age at transplantation and age at sampling) were analyzed. We found that very long-term patients were characterized by a significantly lower percentage of total B cells, a significantly higher proportion of CD24HiCD38Lo memory B cells, significantly fewer CD24LoCD38Lo naive B cells, and a significantly lower proportion of PD1HiCCR7Lo Tfh lymphocytes than more recently transplanted patients. This phenotype is associated with a positive composite score of tolerance in patients transplanted for more than 25 years. Thus, our study suggests a dual phenotype in very long-term kidney transplanted patients with an immunological profile associated with low rejection risk.