Distinct immunopathological mechanisms of EBV-positive and EBVnegative posttransplant lymphoproliferative disorders
Résumé
EBV‐positive and EBV‐negative post‐transplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV‐positive and 39 EBV‐negative PTLD patients of the K‐VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013‐2019), and compared them to PTLD‐free Transplant Controls (TC, n=21). We measured absolute lymphocyte counts (n=108), analyzed NK‐ and T‐cell phenotypes (n=49 and 94) and performed EBV‐specific functional assays (n=16 and 42) by multiparamenter flow cytometry and ELISpot‐IFNγ assays (n=50). EBV‐negative PTLD patients, NK cells overexpressed Tim‐3; the 2‐year progression‐free survival was poorer in patients with a CD4 lymphopenia (CD4+<300 cells/mm3, p<0.001). EBV‐positive PTLD patients presented a profound NK‐cell lymphopenia (median=60 cells/mm3) and a high proportion of NK cells expressing PD‐1 (vs TC, p=0.029) and apoptosis markers (vs TC, p<0.001). EBV‐specific T cells of EBV‐positive PTLD patients circulated in low proportions, showed immune‐exhaustion (p=0.013 vs TC) and poorly recognized the N‐terminal portion of EBNA‐3A viral protein. Altogether, this broad comparison of EBV‐positive and EBV‐negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.
Domaines
Immunologie
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