ACUTE KIDNEY GRAFT-REJECTION - A MORPHOLOGICAL AND IMMUNOHISTOLOGICALSTUDY ON ZERO-HOUR AND FOLLOW-UP BIOPSIES WITH SPECIAL EMPHASIS ON CELLULAR INFILTRATES AND ADHESION MOLECULES

Serial biopsies from 41 consecutive renal allotransplanted patients we re evaluated in order to obtain pretransplant data as well as informat ion on well-functioning and acutely rejecting grafts. Each patient ser ved as his own control. Thirty-five patients were followed according t o the schedule which included biopsy prior to transplantation, shortly after opening of reanastomosis, at least once postoperatively (days 7 -10), and furthermore whenever clinically indicated. The morphological evaluation was in each case combined with immunofluorescence (to dete ct immunoglobulins and complement fractions) and immunohistochemistry with a wide panel of monoclonal antibodies for T cells (CD2, CD3, CD4, CD8, gamma delta), B cells (CD20, CD22), macrophages (CD68, MAC387) N K cells (leu-7, CD16), activation markers (IL-2-R, Ki-67, transferrin- R), MHC antigens (HLA-ABC, HLA-DR), adhesion molecules (ICAM-1, VCAM-1 , ELAM-1, PADGEM, VLA-4, LFA-1 alpha/beta), and growth factors (EGF, T GF-alpha EGF-R). When 132 biopsies and 10 failed allografts were exami ned, no specific morphological or immunohistological parameter predict ive of rejection or graft outcome could be found. Morphology in follow -up biopsies from non-rejecting and rejecting patients revealed a cont inuum of inflammatory changes, and several non-rejecting cases demonst rated cellular inflammatory infiltrates which could not be discriminat ed from those seen in acute rejection. Of the patients 44% had acute r ejection accompanied by increased infiltration of T cells and macropha ges showing enhanced IL-2-R expression, increased tubular and endothel ial staining for MHC class II, ICAM-1, and VCAM-1, and strong leukocyt ic expression of VLA-4 and LFA-1 alpha/beta.