Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages

• Published in: Journal of the American Society of Nephrology 1999-07, Vol.10 (7), p.1582-1589
• Main Authors: GRIMM, P. C, MCKENNA, R, NICKERSON, P, RUSSELL, M. E, GOUGH, J, GOSPODAREK, E, BIN LIU, JEFFERY, J, RUSH, D. N
• Format: Article
• Language: English
• Subjects: Acute Disease; Antigens, CD - metabolism; Biological and medical sciences; Calcium-Binding Proteins - metabolism; DNA-Binding Proteins; Female; Graft Rejection - etiology; Graft Rejection - immunology; Graft Rejection - pathology; Humans; Kidney Transplantation - adverse effects; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Macrophage Activation; Macrophages - immunology; Macrophages - pathology; Male; Medical sciences; Microfilament Proteins; Phenotype; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.v1071582

It has been reported previously that one-third of protocol renal biopsies in asymptomatic, biochemically stable renal transplant recipients in the first 6 mo show unsuspected subclinical graft rejection (both infiltrate and tubulitis) and that subclinical rejection is a risk factor for chronic renal dysfunction. This study was performed to determine whether differences in phenotype or activation status of graft-infiltrating cells underlie these different manifestations of acute rejection. Biopsies with normal histology (n = 10), subclinical rejection (n = 13), and clinical rejection (n = 9) were studied using immunohistochemistry and computerized image analysis. Subclinical and clinical rejections had similar histologic Banff scores. Univariate analysis showed a trend for a higher infiltration with CD8+ (P = 0.053) and CD68+(P = 0.06) cells in clinical rejection. Of the activation markers studied (CD25, perforin, tumor necrosis factor-alpha), only allograft inflammatory factor-1+-activated macrophages were significantly (P = 0.014) increased in the infiltrate of clinical rejection biopsies. These data suggest that activated macrophages or their products are responsible for acute renal dysfunction associated with clinical rejection episodes.