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Distribution and variability of antiglobulin PRA values
Abstracts
125
C-6.5 #133
DISTRIBUTION AND VARIABILITY OF ANTIGLOBULIN PRA VALUES. JL Morrisey, Southwest Iranunodiagnostics, Inc., San Antonio, TX. The distribution of AHG-based PRA values among patients on a cadaveric waiting list of 115 (76 Hispanics, 22 Caucasians, 15 Blacks, 2 Orientals; 80 primary grafts and 35 regrafts) was 24% of patients always having <11% PRAs, 23% of patients mostly having <11% PRAs, 13% of patients always having between 10% and 80% PRAs, 6% of patients mostly having between 10% and 80% PRAs, 22% of patients always having >80% PRAs, and 12% of patients not classified due to less than 3 PRAs. Among those patients always having less than <11% PRA (category A) and those patients mostly having <11% PRA (category B), there was a subset who had a few PRAs elevated above a baseline of 0 to 3%. When the elevated PRAs in the subset of patients in category A were compared, for 8 of the ii patients the PRA reactivities appeared non-specific and unrelated. When the elevated PRAs in the subset of patients in category B were compared, a third of the patients showed unrelated reactivity a third showed poorly defined, related reactivity, and a third showed related, identifiable reactivity. When these elevated sera were used in cadaveric crossmatches, those with non-specific and unrelated reactivity gave predominantly negative results while those sera with poorly defined or identifiable related reactivity gave a higher percentage of positive results. The non-specific reactivity in sera of patients in categories A and B may be due to technical problems or non-specific IgG bound to the unseparated lymphocytes used in the screen.
C-6.5 #134
INTRAVENOUS IMMUNOGLOBULIN (IvIg) CAN DECREASE THE PRA LEVELS OF HIGHLY SENSITIZED PATIENTS. RM Britton and JA Mclntyre, Histocompatibility Laboratory, Methodist Hospital of Indiana, Indianapolis, IN. Preformed alloantibodies remain a serious contraindication for many patients awaiting solid organ transplantation. Ivlg (10% Gamimune, Miles, Inc) in our in vitro studies has proven to be effective in reducing panel reactive antibodies (PRA) for many highly sensitized patients. In vivo use of this drug was shown by Tyan et. al. (Transplantation 57:553, 1994), to allow successful transplantation in patients who otherwise might never be transplanted. Sera from 14 highly sensitized renal patients (6, 1st transplant, and 8, 2nd transplant) with PRA's ranging from 46-99 % C~ = 73 %) were selected for in vitro PRA blocking experiments utilizing equal volumes of 10% Ivlg and patient serum. For vehicle control, a glycine buffer was used. PRA reduction was assessed by two visual cytotoxicity methods, Amos modified (which incorporates a wash step) and the standard NIH method (no wash) against a 60 member cell panel. Flow cytometry (FACS) was also used to monitor Ivlg effects. The results of both visual methods showed a dose dependent reduction in PRA, but a significant difference was demonstrated between the Amos modified (x reduction: 11%, range: 0-54%) and the NIH methods (~ reduction: 25 %, range: 0-78%). FACS results were consistent and always showed a decrease in antibody reactivity as measured by mean channel shifts (log scale) of 10-322 ~- = 117) for IgG and 4-50 ~ = 20) for IgM. Several patients' PRA levels which did not appear to be reduced by visual cytotoxicity, were significantly reduced when assessed by FACS. In summary, Ivlg treatment of highly sensitized patients may prove to be an effacious approach to solid organ transplantation and provide many heretofore untransplantable patients with new opportunities.
125
C-6.5 #133
DISTRIBUTION AND VARIABILITY OF ANTIGLOBULIN PRA VALUES. JL Morrisey, Southwest Iranunodiagnostics, Inc., San Antonio, TX. The distribution of AHG-based PRA values among patients on a cadaveric waiting list of 115 (76 Hispanics, 22 Caucasians, 15 Blacks, 2 Orientals; 80 primary grafts and 35 regrafts) was 24% of patients always having <11% PRAs, 23% of patients mostly having <11% PRAs, 13% of patients always having between 10% and 80% PRAs, 6% of patients mostly having between 10% and 80% PRAs, 22% of patients always having >80% PRAs, and 12% of patients not classified due to less than 3 PRAs. Among those patients always having less than <11% PRA (category A) and those patients mostly having <11% PRA (category B), there was a subset who had a few PRAs elevated above a baseline of 0 to 3%. When the elevated PRAs in the subset of patients in category A were compared, for 8 of the ii patients the PRA reactivities appeared non-specific and unrelated. When the elevated PRAs in the subset of patients in category B were compared, a third of the patients showed unrelated reactivity a third showed poorly defined, related reactivity, and a third showed related, identifiable reactivity. When these elevated sera were used in cadaveric crossmatches, those with non-specific and unrelated reactivity gave predominantly negative results while those sera with poorly defined or identifiable related reactivity gave a higher percentage of positive results. The non-specific reactivity in sera of patients in categories A and B may be due to technical problems or non-specific IgG bound to the unseparated lymphocytes used in the screen.
C-6.5 #134
INTRAVENOUS IMMUNOGLOBULIN (IvIg) CAN DECREASE THE PRA LEVELS OF HIGHLY SENSITIZED PATIENTS. RM Britton and JA Mclntyre, Histocompatibility Laboratory, Methodist Hospital of Indiana, Indianapolis, IN. Preformed alloantibodies remain a serious contraindication for many patients awaiting solid organ transplantation. Ivlg (10% Gamimune, Miles, Inc) in our in vitro studies has proven to be effective in reducing panel reactive antibodies (PRA) for many highly sensitized patients. In vivo use of this drug was shown by Tyan et. al. (Transplantation 57:553, 1994), to allow successful transplantation in patients who otherwise might never be transplanted. Sera from 14 highly sensitized renal patients (6, 1st transplant, and 8, 2nd transplant) with PRA's ranging from 46-99 % C~ = 73 %) were selected for in vitro PRA blocking experiments utilizing equal volumes of 10% Ivlg and patient serum. For vehicle control, a glycine buffer was used. PRA reduction was assessed by two visual cytotoxicity methods, Amos modified (which incorporates a wash step) and the standard NIH method (no wash) against a 60 member cell panel. Flow cytometry (FACS) was also used to monitor Ivlg effects. The results of both visual methods showed a dose dependent reduction in PRA, but a significant difference was demonstrated between the Amos modified (x reduction: 11%, range: 0-54%) and the NIH methods (~ reduction: 25 %, range: 0-78%). FACS results were consistent and always showed a decrease in antibody reactivity as measured by mean channel shifts (log scale) of 10-322 ~- = 117) for IgG and 4-50 ~ = 20) for IgM. Several patients' PRA levels which did not appear to be reduced by visual cytotoxicity, were significantly reduced when assessed by FACS. In summary, Ivlg treatment of highly sensitized patients may prove to be an effacious approach to solid organ transplantation and provide many heretofore untransplantable patients with new opportunities.