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P128 Infections increase sensitization among ventricular assist device recipients
148
P128
Abstracts / Human Immunology 78 (2017) 51–254
INFECTIONS INCREASE SENSITIZATION AMONG VENTRICULAR ASSIST DEVICE RECIPIENTS Pamela M. Kimball a, Felecia McDougan b. aMedical College of Virginia, Richmond, VA, United States b VCUHealth Systems, Richmond, VA, United States.
;
Aim: Bacterial infections are common following ventricular assist device (VAD) implantation. We anecdotally noted that VAD recipients who had infections appeared to have longer waittimes to heart transplantation than patients without infections. We questioned whether infections might increase sensitization and promote longer waittimes. This premise was evaluated by comparing sensitization before and after VAD placement in patients on the heart waitlist. Methods: Sixty-three waitlisted patients who received VADs were selected. All patients had P1 bacterial infection within 12 months post-VAD. Monthly serums had been collected pre and post-VAD and previously tested for PRA and specificity using luminex. The following data was collected: PRA against Class I and II, cPRA (MFI > 5000 were unacceptable) and DSA for those transplanted. Waitlist time to transplant was compared with 9 patients without infections post-VAD. Results: Patients were 50 ± 14 yo, 56% African American, 69% male. Infections occurred within 30 days of VAD placement in 69% patients; 46% had multiple infections. 40% of patients showed no change in PRA. Mean PRA against Class I (4.6 ± 1.8% vs. 15 ± 25%, p < 0.001) and Class II (4.0 ± 1.7% vs. 13 ± 25%, p < 0.001) was lower pre- vs. post-infection. The frequency of patients with PRA > 10% was greater post-infection (25% vs. 47%, p = 0.02). Specificity was more directed against Class I than Class II in pre-(24% vs. 10%, p < 0.05) and postinfection (44% vs. 27%, p < 0.05). cPRA was markedly elevated post-infection: cPRA against Class I increased from 6% to 25% (p = 0.003) and against Class II from 0% to 11% (p = 0.006). Average time to see change in PRA was 1.5 ± 0.5 months post infection.33 patients underwent heart transplantation. Percent of patients with DSA was measured between pre-VAD and post infection/pre-transplant serums. Fewer patients had DSA in pre-VAD than pre-transplant serum (3% vs. 28%, p = 0.003).Compared to non-infected patients, waittime to transplantation increased among patients with cPRA > 0% (239 vs. 365 days) and was highest among those also with DSA (465 days). Conclusions: Bacterial infections are common after VAD placement and may be an unexpected stimulus of sensitization that may increase waittimes to heart transplantation.
P129
DEALING WITH FALSE-POSITIVE VIRTUAL CROSSMATCH IN LUNG RECIPIENTS Olga A. Timofeeva, Steven S. Geier, Mohammed A. Kashem, David Grogan, Suresh Keshavamurthy, Jesus Gomez-Abraham, Francis Cordova, Yoshiya Toyoda. Temple University School of Medicine and Hospital, Philadelphia, PA, United States. Aim: Virtual crossmatch (VXM) has increased non-local organ utilization and improved clinical outcomes for sensitized lung patients. However, the concordance between VXM and cell-based crossmatch is not absolute because Single Antigen Bead (SAB) assay is prone to both false-negative and false-positive reactions. Since false-positive antibody specificities may unnecessarily deny an organ based on VXM, the goal of this study was to evaluate what additional testing may be warranted to recognize such reactions and to improve virtual crossmatch accuracy. Methods: All sera were pre-treated with EDTA to inactivate complement in order to avoid prozon-like effect and were analyzed by SAB. A positive VXM was defined as the presence of donor specific antibodies based on SAB that would result in unacceptably positive Flow Crossmatch (FCXM). FCXM was done using 3-color analysis on a 1024 channel scale. All sera was retrospectively tested by FlowPRA Screen and LSPRA (phenotype bead) assays to rule out antibodies against denatured HLA epitopes detected by SAB. Results: Of 58 consecutive VXM performed during July-December 2016 for lung candidates with CPRA > 10%, 28 had no DSAs or had acceptably weak DSAs and were predicted to result in negative or acceptably low positive FCXM. Other 30 VXM had one or more strong DSAs and were predicted to result in unacceptably positive FCXM and the organ offers were refused. Additional antibody testing showed that only 23 out of 30 VMXs should have been called positive. The other 7 VXM were called unacceptably positive due to the presence of antibody against denatured antigens. Three patients had antibodies against class I denatured antigens (MFI ranging 2500–3500) and four patients had antibodies against class II denatured antigens (MFI ranging 2000–14,000). After using LSPRA and FlowPRA Screen assays, the antibody against denatured antigens were removed from the list of UA and 5 out of 7 patients were successfully transplanted. Conclusions: We found that at our center 12% VXM are false-positive due to the presence of antibodies against denatured antigens detected by SAB. Multiple antibody testing platforms, including SAB, LSPRA, and FlowPRA Screen, can be used for antibody characterization to avoid erroneous assignment of UA that may lead to an unnecessary organ offer refusal.
P128
Abstracts / Human Immunology 78 (2017) 51–254
INFECTIONS INCREASE SENSITIZATION AMONG VENTRICULAR ASSIST DEVICE RECIPIENTS Pamela M. Kimball a, Felecia McDougan b. aMedical College of Virginia, Richmond, VA, United States b VCUHealth Systems, Richmond, VA, United States.
;
Aim: Bacterial infections are common following ventricular assist device (VAD) implantation. We anecdotally noted that VAD recipients who had infections appeared to have longer waittimes to heart transplantation than patients without infections. We questioned whether infections might increase sensitization and promote longer waittimes. This premise was evaluated by comparing sensitization before and after VAD placement in patients on the heart waitlist. Methods: Sixty-three waitlisted patients who received VADs were selected. All patients had P1 bacterial infection within 12 months post-VAD. Monthly serums had been collected pre and post-VAD and previously tested for PRA and specificity using luminex. The following data was collected: PRA against Class I and II, cPRA (MFI > 5000 were unacceptable) and DSA for those transplanted. Waitlist time to transplant was compared with 9 patients without infections post-VAD. Results: Patients were 50 ± 14 yo, 56% African American, 69% male. Infections occurred within 30 days of VAD placement in 69% patients; 46% had multiple infections. 40% of patients showed no change in PRA. Mean PRA against Class I (4.6 ± 1.8% vs. 15 ± 25%, p < 0.001) and Class II (4.0 ± 1.7% vs. 13 ± 25%, p < 0.001) was lower pre- vs. post-infection. The frequency of patients with PRA > 10% was greater post-infection (25% vs. 47%, p = 0.02). Specificity was more directed against Class I than Class II in pre-(24% vs. 10%, p < 0.05) and postinfection (44% vs. 27%, p < 0.05). cPRA was markedly elevated post-infection: cPRA against Class I increased from 6% to 25% (p = 0.003) and against Class II from 0% to 11% (p = 0.006). Average time to see change in PRA was 1.5 ± 0.5 months post infection.33 patients underwent heart transplantation. Percent of patients with DSA was measured between pre-VAD and post infection/pre-transplant serums. Fewer patients had DSA in pre-VAD than pre-transplant serum (3% vs. 28%, p = 0.003).Compared to non-infected patients, waittime to transplantation increased among patients with cPRA > 0% (239 vs. 365 days) and was highest among those also with DSA (465 days). Conclusions: Bacterial infections are common after VAD placement and may be an unexpected stimulus of sensitization that may increase waittimes to heart transplantation.
P129
DEALING WITH FALSE-POSITIVE VIRTUAL CROSSMATCH IN LUNG RECIPIENTS Olga A. Timofeeva, Steven S. Geier, Mohammed A. Kashem, David Grogan, Suresh Keshavamurthy, Jesus Gomez-Abraham, Francis Cordova, Yoshiya Toyoda. Temple University School of Medicine and Hospital, Philadelphia, PA, United States. Aim: Virtual crossmatch (VXM) has increased non-local organ utilization and improved clinical outcomes for sensitized lung patients. However, the concordance between VXM and cell-based crossmatch is not absolute because Single Antigen Bead (SAB) assay is prone to both false-negative and false-positive reactions. Since false-positive antibody specificities may unnecessarily deny an organ based on VXM, the goal of this study was to evaluate what additional testing may be warranted to recognize such reactions and to improve virtual crossmatch accuracy. Methods: All sera were pre-treated with EDTA to inactivate complement in order to avoid prozon-like effect and were analyzed by SAB. A positive VXM was defined as the presence of donor specific antibodies based on SAB that would result in unacceptably positive Flow Crossmatch (FCXM). FCXM was done using 3-color analysis on a 1024 channel scale. All sera was retrospectively tested by FlowPRA Screen and LSPRA (phenotype bead) assays to rule out antibodies against denatured HLA epitopes detected by SAB. Results: Of 58 consecutive VXM performed during July-December 2016 for lung candidates with CPRA > 10%, 28 had no DSAs or had acceptably weak DSAs and were predicted to result in negative or acceptably low positive FCXM. Other 30 VXM had one or more strong DSAs and were predicted to result in unacceptably positive FCXM and the organ offers were refused. Additional antibody testing showed that only 23 out of 30 VMXs should have been called positive. The other 7 VXM were called unacceptably positive due to the presence of antibody against denatured antigens. Three patients had antibodies against class I denatured antigens (MFI ranging 2500–3500) and four patients had antibodies against class II denatured antigens (MFI ranging 2000–14,000). After using LSPRA and FlowPRA Screen assays, the antibody against denatured antigens were removed from the list of UA and 5 out of 7 patients were successfully transplanted. Conclusions: We found that at our center 12% VXM are false-positive due to the presence of antibodies against denatured antigens detected by SAB. Multiple antibody testing platforms, including SAB, LSPRA, and FlowPRA Screen, can be used for antibody characterization to avoid erroneous assignment of UA that may lead to an unnecessary organ offer refusal.