title: Prognostic value of cytotoxic T-lymphocytes and CD40 in biopsies with early renal allograft rejection.
abstract: After renal transplantation, different immunological and non-immunological factors lead to long-term allograft deterioration. Acute rejection episodes are one risk factor for chronic renal allograft dysfunction (CRAD). Following the current Banff classification the histological grade in acute rejection episodes is of limited prognostic value, therefore, additional morphological surrogate markers would be helpful. We investigated the biopsies of 91 patients with early acute rejection episodes for the immunohistochemical expression of key molecules (perforin, granzyme B, TIA-1, CD40) in the T cell-mediated rejection process. Staining results were correlated to long-term allograft outcome. Patients with greater than 2% of granzyme B or greater than 25% of CD40-positive cells in the interstitial infiltrate showed significantly shorter allograft survival. Patients with a CD40-positive vascular rejection or greater than 2% of granzyme B-positive cells in the interstitial infiltrate were significantly correlated with an earlier onset of CRAD. Our findings provide potential morphological surrogate markers in biopsies with early acute rejection episodes after renal transplantation. These could become part of combined clinical and histological algorithms, allowing patient-specific risk estimation and customized therapy options to be made.
authors.affiliation: Institute of Pathology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, 30625, Hanover, Germany. mengel.michael@mh-hannover.de
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Imke
authors.initials: I
authors.lastname: Mueller
authors.forename: Matthias
authors.initials: M
authors.lastname: Behrend
authors.forename: Reinhard
authors.initials: R
authors.lastname: von Wasielewski
authors.forename: Joerg
authors.initials: J
authors.lastname: Radermacher
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D019013:CD40 Antigens / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D006085:Graft Survival / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000473:pathology*
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016601:RNA-Binding Proteins; D054353:Perforin; C076751:TIAL1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases