title: Antibody-mediated rejection with a striking interstitial monocyte/macrophage infiltration in a renal allograft under FTY720 treatment.
abstract: FTY720, a novel immunomodulator, causes rapid temporary depletion of peripheral-blood lymphocytes, inducing their sequestration in secondary lymphoid organs. FTY720 is effective in animal models of transplantation and is under evaluation for use in human transplantation. We report a 48-year-old renal transplant recipient who developed acute antibody-mediated rejection under a high-dose FTY720 (5 mg/d), low-dose cyclosporine A, and prednisone treatment protocol. A T-cell antihuman globulin and National Institutes of Health extended B-cell cross-match with donor cells were negative before transplantation. At 10 weeks posttransplantation, serum creatinine level increased and a renal biopsy showed a striking interstitial CD68(+) monocyte/macrophage infiltration with C4d staining of peritubular capillaries. Flow panel reactive antibody levels were positive in the recipient's serum for class I (9%) and class II (75%). The positive panel reactive antibody levels and presence of C4d in peritubular capillaries justified the diagnosis of antibody-mediated rejection. However, the presence of macrophage-rich interstitial infiltrate suggested a contribution of cellular rejection. The morphological characteristic of rejection with a striking interstitial CD68(+) monocyte/macrophage infiltration with paucity of T cells is very unusual and may reflect a unique effect of FTY720 therapy.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. bsis@ualberta.ca
authors.forename: Banu
authors.initials: B
authors.lastname: Sis
authors.forename: Richard
authors.initials: R
authors.lastname: Grynoch
authors.forename: Allan G
authors.initials: AG
authors.lastname: Murray
authors.forename: Patricia
authors.initials: P
authors.lastname: Campbell
authors.forename: Kim
authors.initials: K
authors.lastname: Solez
mesh_terms: D000906:Antibodies / Q000009:adverse effects*; D002465:Cell Movement / Q000276:immunology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology*; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D015796:HLA-B27 Antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C052238:HLA-DR14; D015804:HLA-DR4 Antigen; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine