How to Diagnose Chronic Rejection. A Study in Porcine Intestinal Allografts

Abstract

Kuusanmäki P, Lauronen J, Paavonen T, Pakarinen M, Yilmaz S, Häyry P, Halttunen J. How to Diagnose Chronic Rejection. A Study in Porcine Intestinal Allografts. Scand J Immunol 1997;46:514-519 Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.

The relationship between morphology and disaccharidase activity in ischemia- reperfusion injured intestine.

“…Promising results of DA changes regarding intestinal graft rejection have been shown in other studies, although discrepant results are seen as well. While Kaufman et al (1998) showed that assessment of mucosal disaccharidase activity provides no additional useful information concerning efficacy of anti-rejection therapy as compared to histologic analysis alone, other studies recommend DA assessment as an appropriate marker for study and verification of acute (Kuusanmäki et al, 1996) as well as chronic rejection (Kuusanmäki et al, 1997). Notably a correlation with morphological status was detected for sucrose and maltase, but not when lactase was measured (Teitelbaum et al, 1989).…”

Airway Goblet Cells and Respiratory Epithelial Injury in an Animal Model of Obliterative Airways Disease (OAD)

“…Kuusanmaki et al. (11) studied porcine small bowel allografts during immunosuppressive therapy. The authors reported that by the 12th week, there was epithelial vacuolation and goblet cell loss.…”

The Physiology of the Transplanted Small Bowel: An Overview with Insight into Graft Function

“…Accordingly, the absorption of glucose, maltose, and fatty acids has been shown to decrease rapidly during acute rejection (172,181,182). Moreover, with the current immunosuppressive armamentarium unavoidable chronic rejection gradually obliterates the mesenteric vessels (183), probably resulting in a gradual decrease in blood flow and, finally, the loss of absorptive function. The effects of chronic allograft rejection on small-intestinal function should serve as an important and fruitful source for future research.…”