title: An Acute Cellular Rejection With Detrimental Outcome Occurring Under Belatacept-Based Immunosuppressive Therapy: An Immunological Analysis.
abstract: Belatacept has been associated with an increased acute rejection rate after kidney transplantation. This case report sheds light on the possible immunological mechanisms underlying this phenomenon by analyzing the immunological mechanisms in patient serum, peripheral blood mononuclear cells, rejected kidney tissue, and graft infiltrating cells.
  
  
  
  A 61-year-old woman treated with belatacept, who received her first kidney transplant from her husband was admitted with an acute, vascular rejection 56 days after transplantation which necessitated a transplantectomy. Histology and immunohistochemistry were performed on biopsy and explant tissue. CD86 expression on peripheral monocytes was assessed. Using Ficoll density methods, peripheral blood, and graft infiltrating lymphocytes were isolated and phenotyped.
  
  
  
  The explant showed a vascular rejection (Banff ACR grade III) and a perivascular infiltrate mostly consisting of T cells. No evidence for antibody-mediated rejection was found. In contrast to the peripheral blood monocytes, CD86 was still expressed by part of the mononuclear cells in the explant.Isolated graft cells were mostly CCR7-CD45RO+ effector memory CD4 and CD8 T cells (60-70%). CD28-positive as CD28-negative T cells were present in the explant, showing a great IFN-γ production capacity and expressing granzyme B.
  
  
  
  We postulate that this glucocorticoid-resistant cellular rejection occurring under belatacept was predominantly mediated by cytotoxic memory T cells, which are less susceptible to costimulatory blockade by belatacept, or resulted from incomplete CD80/86 blockade at the tissue level.
authors.affiliation: 1 Department of Internal Medicine, Section Transplantation and Nephrology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 2 Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. 3 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. 4 Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: de Graav
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Marjolein
authors.initials: M
authors.lastname: Dieterich
authors.forename: Rens
authors.initials: R
authors.lastname: Kraaijeveld
authors.forename: Hannie
authors.initials: H
authors.lastname: Douben
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Joke I
authors.initials: JI
authors.lastname: Roodnat
authors.forename: Marian C
authors.initials: MC
authors.lastname: Clahsen-van Groningen
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D051940:B7-2 Antigen / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection; D006801:Humans; D007107:Immune System; D007156:Immunologic Memory; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D012306:Risk; D013601:T-Lymphocytes / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D051940:B7-2 Antigen; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069594:Abatacept