This review discusses recent findings that are changing and expanding the spectrum of pathologic changes associated with antibodies directed against renal allografts.
This review focuses on four lesions: subclinical antibody-mediated rejection (AMR), C4d-negative AMR, intimal arteritis, and arterial intimal fibrosis. A number of studies have identified morphologic lesions of AMR in protocol biopsies of normally functioning renal allografts, particularly in sensitized recipients, that correlate with subsequent development of chronic changes in the graft, including transplant glomerulopathy. These same studies as well as molecular studies of indication biopsies of conventional renal allografts have noted evidence of microvascular injury, which, in the presence of donor-specific antibodies (DSAs) but the absence of C4d deposition in peritubular capillaries, is associated with development of transplant glomerulopathy and graft loss. Finally, recent studies suggest that intimal arteritis, previously felt to represent a lesion of cell-mediated rejection, and bland arterial intimal fibrosis, resembling arteriosclerosis, may in some cases be manifestations of DSA-induced graft injury.
Incorporation of these newly recognized lesions of AMR into a working diagnostic schema with sufficient sensitivity and specificity to minimize undertreatment and overtreatment of patients is an important challenge currently faced by renal pathologists and transplant clinicians.
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
Correspondence to Mark Haas, MD, PhD, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 8742, Los Angeles, CA 91403, USA. Tel: +1 310 248 6695; fax: +1 310 423 5881; e-mail: firstname.lastname@example.org