title: The significance of the anti-class I response. II. Clinical and pathologic features of renal transplants with anti-class I-like antibody.
abstract: Although the ability of preformed anti-class I antibodies to mediate hyperacute rejection is well established, their pathogenic role in acute rejection remains ill-defined. We set out to identify patients with anti-class I against donor cells and to define the clinical and pathological features of such patients. We collected sera pretransplant and in the first 3 months posttransplant from 64 renal transplant recipients (59 cadaver donors and 5 one-haplotype matched living-related donors). We assayed the sera for class I-like antibody against donor T cells in complement-dependent microcytotoxicity, with crossmatches against autologous T cells to exclude auto-antibodies. All pretransplant sera were negative against donor T cells. Of the 797 sera tested posttransplant, 131/195 sera from 13 patients were positive, and 602 sera from 51 patients were negative. All patients who formed anti-class I underwent rejections compared with only 41% of patients with no anti-class I detected (P less than 0.0005). More rejections in patients with anti-class I were classed as severe (12/15 [80%] compared with 9/28 [32%] P less than 0.005), and graft loss was significantly higher (5/13 vs. 2/51; P less than 0.002). Rejections associated with anti-class I occurred earlier; more frequently developed oliguria (35% versus 10%) and required dialysis (40% versus 10%) and biopsies (10/13 vs. 6/28); and had a higher rate of rise in serum creatinine (249 versus 79 microns/L in the first 48 hr). Biopsies during anti-class I positive rejections more frequently displayed endothelial injury in the microcirculation, neutrophils in the glomeruli and/or peritubular capillaries, and fibrin deposition in glomeruli or blood vessels. The biopsies in anti-class I negative rejection episodes tended to have tubulitis, interstitial infiltration, and blasts, suggesting that these lesions reflect T-cell-mediated mechanisms. We conclude that patients with antibody against donor class I had more severe rejection, probably because anti-class I injuries the endothelium of small blood vessels of the graft, leading to rapid functional deterioration. We believe that anti-class I may be a major factor in some severe rejection episodes.
authors.affiliation: Division of Nephrology and Immunology, University of Alberta Hospitals, Edmonton, Canada.
authors.forename: P F
authors.initials: PF
authors.lastname: Halloran
authors.forename: J
authors.initials: J
authors.lastname: Schlaut
authors.forename: K
authors.initials: K
authors.lastname: Solez
authors.forename: N S
authors.initials: NS
authors.lastname: Srinivasa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D001706:Biopsy; D002648:Child; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D015395:Histocompatibility Antigens Class I