(F)Utility of the physical crossmatch for living donor evaluations in the age of the virtual crossmatch.

Flow cytometric crossmatches (FCXM) are routinely performed to support living-donor renal transplantation. While long a laboratory mainstay, a physical crossmatch is costly, time consuming, and frequently poses interpretative conundrums with both false-positive and false- negative results. Given the increased utilization of the virtual crossmatch (vXM) in the deceased donor setting, our aim was to assess its utility in living donor evaluations. We reviewed 100 living donor FCXMs and retrospectively performed a vXM for each pair. Seventy-five (75) cases were concordant, (i.e., FCXM-/vXM- or FCXM+/vXM+) while 25 cases were discordant; Five were vXM+/FCXM- and 20 were FCXM+/vXM-. Since donor-specific antibodies (DSA) were not detected in the 20 FCXM+/vXM- cases, these were interpreted as false-positive, i.e., due to non-HLA antibodies. Importantly, none of these patients, when transplanted across a positive FCXM, experienced early antibody mediated rejection or subsequently developed HLA DSA. These data reveal that, for the vast majority of living donor evaluations, a vXM is an acceptable vetting procedure.

[1]  T. Mohanakumar,et al.  Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: a 30-month analysis in living donor kidney transplantation. , 2010, Human immunology.

[2]  A. Stiggelbout,et al.  Difference in quality of life, fatigue and societal participation between living and deceased donor kidney transplant recipients , 2013, Clinical transplantation.

[3]  R. Bray,et al.  Pronase improves detection of HLA antibodies in flow crossmatches. , 2001, Transplantation proceedings.

[4]  R. Bray,et al.  Understanding solid-phase HLA antibody assays and the value of MFI. , 2017, Human immunology.

[5]  F. Christiansen,et al.  Transnational validation of the Australian algorithm for virtual crossmatch allocation in kidney paired donation. , 2013, Human immunology.

[6]  P. Terasaki,et al.  “Natural” Human Leukocyte Antigen Antibodies Found in Nonalloimmunized Healthy Males , 2008, Transplantation.

[7]  F. Mach,et al.  The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells. , 2001, Swiss medical weekly.

[8]  Santa Jeremy Ono,et al.  Modulation of MHC class II expression in human cells by dexamethasone. , 1995, Cellular immunology.

[9]  M. Mihatsch,et al.  Pretransplant Risk Assessment in Renal Allograft Recipients Using Virtual Crossmatching , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  K. Kokko,et al.  Transplanting the Highly Sensitized Patient: The Emory Algorithm , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  U. Ott,et al.  General insufficiency of the classical CDC-based crossmatch to detect donor-specific anti-HLA antibodies leading to invalid results under recipients' medical treatment or underlying diseases. , 2012, Histology and histopathology.

[12]  T. Fishbein,et al.  Successful Isolated Intestinal Transplantation in Sensitized Recipients With the Use of Virtual Crossmatching , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  K. Mekeel,et al.  Root cause analysis of limitations of virtual crossmatch for kidney allocation to highly-sensitized patients. , 2017, Human immunology.

[14]  M. Farzandipour,et al.  A review on laboratory tests’ utilization: A trigger for cutting costs and quality improvement in health care settings , 2016, Medical journal of the Islamic Republic of Iran.

[15]  P. Terasaki,et al.  Epitopes of HLA antibodies found in sera of normal healthy males and cord blood. , 2008, Clinical transplants.

[16]  M. Gerbase-DeLima,et al.  Antibodies against denatured HLA class II molecules detected in luminex-single antigen assay. , 2013, Human immunology.

[17]  David M. Conrad,et al.  Rapid optimized flow cytometric crossmatch (FCXM) assays: The Halifax and Halifaster protocols. , 2018, Human immunology.

[18]  H. Gebel,et al.  Of Cells and Microparticles: Assets and Liabilities of HLA Antibody Detection. , 2018, Transplantation.

[19]  D. Phelan,et al.  HLA compatibility assessment and management of highly sensitized patients under the new kidney allocation system (KAS): A 2016 status report from twelve HLA laboratories across the U.S. , 2017, Human immunology.

[20]  R. Redfield,et al.  Virtual HLA Crossmatching as a Means to Safely Expedite Transplantation of Imported Pancreata , 2016, Transplantation.

[21]  A. Jackson,et al.  Variable HLA expression on deceased donor lymphocytes: Not all crossmatches are created equal. , 2015, Human immunology.

[22]  M. Denton,et al.  Twenty‐Year Survivors of Kidney Transplantation , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  P. Terasaki,et al.  Significance of the positive crossmatch test in kidney transplantation. , 1969, The New England journal of medicine.

[24]  P. Nickerson,et al.  Evolution of HLA antibody detection , 2004, Immunologic research.

[25]  Dominique Charron,et al.  Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. , 2010, Journal of the American Society of Nephrology : JASN.

[26]  S. Lepreux,et al.  Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation , 2016, Transplantation.

[27]  L. Rostaing,et al.  Interference of therapeutic antibodies used in desensitization protocols on lymphocytotoxicity crossmatch results. , 2015, Transplant immunology.

[28]  J. Lunz,et al.  The coordination of allocation: Logistics of kidney organ allocation to highly sensitized patients. , 2017, Human immunology.

[29]  E. Cantu,et al.  Role of Flow Cytometry to Define Unacceptable HLA Antigens in Lung Transplant Recipients with HLA-Specific Antibodies , 2006, Transplantation.

[30]  B. Shames,et al.  Renal Transplantation With Final Allocation Based on the Virtual Crossmatch , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[31]  S. Stowell,et al.  Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience. , 2017, Archives of pathology & laboratory medicine.

[32]  L. Sharples,et al.  Ten-Year Experience of Selective Omission of the Pretransplant Crossmatch Test in Deceased Donor Kidney Transplantation , 2010, Transplantation.

[33]  V. Alonso,et al.  Outcomes of pediatric living donor kidney transplantation: A single‐center experience , 2017, Pediatric transplantation.

[34]  M. Suchard,et al.  Luminex-based virtual crossmatching for renal transplantation in South Africa. , 2011, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[35]  J. Steiger,et al.  Clinical Relevance of Pretransplant Donor-Specific HLA Antibodies Detected by Single-Antigen Flow-Beads , 2009, Transplantation.

[36]  M. Stegall,et al.  Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates , 2017, Transplantation.