Correlation of genetic markers of rejection with biopsy findings following human pancreas transplant.
Acute rejection after pancreas transplantation remains a significant problem and contributes to immunologic graft loss. No clinical markers of pancreas rejection have been universally accepted. Recent studies have identified several cytotoxic genes as possible markers of acute rejection in renal and islet cell transplant recipients. However, these markers of rejection have not been evaluated in pancreas transplant recipients. This study evaluated the differential expression of granzyme B, perforin, and human leukocyte antigen (HLA)-DRA in peripheral blood between patients with and without biopsy-proven pancreas rejection (n = 7 per group). Gene expression levels were analyzed using real time reverse transcriptase polymerase chain reaction assays. Expression of these genes in controls (n = 17) with and without type 1 diabetes was also analyzed. Patients with biopsy-proven pancreas rejection had higher levels of granzyme B, perforin, and HLA-DRA than patients who did not have rejection, although the difference was not statistically significant. Moreover, patients with biopsy-proven pancreas rejection had a significantly higher level of granzyme B than control subjects with type 1 diabetes (p <or= 0.03). Our findings suggest that, with additional evaluation of a larger number of patients as well as a longitudinal approach, analyses of granzyme B expression levels in peripheral blood may be shown to be a non-invasive method of monitoring pancreas allograft rejection.
Department of Acute and Chronic Care, College of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA. acashion@utem.edu
Ann
A
Cashion
Omaima
O
Sabek
Carolyn
C
Driscoll
Lillian
L
Gaber
Malak
M
Kotb
Osama
O
Gaber
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology*; D053804:Granzymes; D006684:HLA-DR Antigens / Q000097:blood*; D059805:HLA-DR alpha-Chains; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D016035:Pancreas Transplantation / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D010865:Pilot Projects; D052899:Pore Forming Cytotoxic Proteins; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000097:blood*; D014184:Transplantation, Homologous
D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases