pancreas transplants and HLA matching: A single center experience

90

Abstracts

C-6.3 #167

KIDNEY/PANCREAS TRANSPLANTS AND HLA MATCHING: A SINGLE CENTER EXPERIENCE. JA Wunder 1, JM Hart 1, ST Bartlett 2, WB Bias 1 and MS Leffell1, Johns Hopkins University ~ and University of Maryland2, Baltimore, MD. We have examined the impact of HLA matching on the outcome of 35 combined kidney/pancreas transplants performed at the University of Maryland from 7/91 to 4/93. We evaluated the data for a possible relationship between the degree of HLA mismatch and rejection. Twenty-seven of 35 recipients (77%) experienced at least one rejection episode, while the remaining 8/35 (23%) had none. Twenty four of 35 (69%) experienced early rejection (<3 months postop). Two patients (6%) experienced both early and late rejection episodes. The occurrence of rejection correlated significantly (p < .001) with the degree of HLA mismatch. Those recipients who were mismatched for 3 antigens or less experienced fewer rejection episodes. Severity was classified as mild, moderate or severe based on renal biopsy histology and creatinine levels. Of the patients experiencing rejection episodes, 26% percent of those patients experienced mild rejection episodes, 14% moderate and 29% severe. Severity corresponded significantly (p<.001) with degree of mismatch. Of the 35 recipients, 1 patient died with functioning grafts, 3 lost their pancreas grafts but have functioning kidney grafts, and the remaining 31 are insulin and dialysis independent. In conclusion, the degree of HLA mismatch correlates significantly with both the number and severity of rejection episodes in kidney/pancreas transplants.

C-6.4 #168

ENHANCED, NON-SPECIFIC BINDING OF MURINE IgG ANTIBODIES TO HUMAN MONONUCLEARCELLS SURFACEDURINGACUTE RENALALLOGRAFTREJECTION. M Shabtai,I Ayigad,P Schechter and A Ayalon. Sheba Medical Center. Tel-Aviy University,Sackler School of Medicine,Israel. The activation of T-cells occuring during acute cell mediated allograft rejection(AR)pis associated with changes in configuration and density of activation-linked molecules.These changes may expose sites that are otherwise inaccessible to non specific binding of IgG antibodies.To test this hypothesis we have computed the intensity of non-specific binding of mouse anti-keyhole limpet protein monoclonal IgG antibody to peripheral mononuclear cells in 45 renal allograft recipients prior to transplantion(PTX),during clinical quiescence(CO) and in biopsy-proven AR,Data obtained by two-color flow cytometry were used to compute the intensity of such binding by density analysis, through a mathematical model,based on fluorescence intensity vector analysis,While there was no significant difference in the relative counts of cells binding non-specifically mouse IgG at PTX,CQ and AR (0.3%,0.2% and 0.3% repectively p=n.s),a significant increase in mean cell surface density of bound mouse antibody was observed in AR (193+ 52) compared to CQ (18+9, p=O.O001) and to PTX (26+16 p=O.OOO1).These data suggest that AR is associated with significantly increased intensity of non-specific binding of mouse IgG antibodies to human mononculear cells.Such phenomenon may be the result of the exposure of Fc receptors and possibly other binding sites to non-specific binding.The significance of this phenomenon is uncertain. The identification of such binding sites and the precise nature of cells bearing them is currently under study.