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VIRTUAL PRA AND CROSSMATCHING

VIRTUAL PRA AND CROSSMATCHING. Dolly B. Tyan, PhD Cedars-Sinai Medical Center Los Angeles, CA. PURPOSE OF PRA. TO INFORM THE CLINICIAN/SURGEON OF THE: LIKELIHOOD OF A TRANSPLANT ANTIBODY SPECIFICITY. PRA P anel R eactive A ntibody – ( % ). Relatively uninformative No specificity

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VIRTUAL PRA AND CROSSMATCHING

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  1. VIRTUAL PRA AND CROSSMATCHING Dolly B. Tyan, PhD Cedars-Sinai Medical Center Los Angeles, CA

  2. PURPOSE OF PRA • TO INFORM THE CLINICIAN/SURGEON OF THE: • LIKELIHOOD OF A TRANSPLANT • ANTIBODY SPECIFICITY

  3. PRAPanel Reactive Antibody – (%) • Relatively uninformative • No specificity • Population dependent • Can vary widely by panel tested

  4. PRA VARIABILITY50 cell panel

  5. PRA ANALYSIS BY DIFFERING METHODLOGIES POSITIVENEGATIVE CDC 102 162 AHG-CDC 116 (+13%) 148 ELISA 127 (+10%) 137 FLOW 139 (+10%) 125 Gebel and Bray, Transplantation 69:1370-1374, 2000.

  6. Calculated PRA value Based on: ABSOLUTE antibody specificity and ACTUAL HLA antigen frequencies in donor population INDEPENDENTof the method Virtual PRA

  7. NATIONAL PRA Calculate the antigen frequency of all donors ever typed in UNET database

  8. CALCULATED PRA –STANDARDIZED

  9. Conclusions • Virtual PRA antibody detection must: • Be Sensitive and HLA-Specific • Be able to Predict the final crossmatch • Be able to identify ALL unacceptable (avoid) antigens • (A-, B-, Cw, DRB1, DQB1, DP??) • Requires accurate typing of deceased donors • Incorporate Both Class I and Class II specificities • Current definition of PRA must change: • Need local/national donor pool antigen frequencies • Incorporate both Class I and II antigens • Results in National PRA Equivalence

  10. PURPOSE OF CROSSMATCH • TO INFORM THE CLINICIAN/SURGEON OF THE RISK* FOR: • PRESENCE OF DSA (DONOR SPECIFIC ANTIBODIES) • HYPERACUTE REJECTION • HUMORAL REJECTION * (not contraindication)

  11. CAN WE DO A VIRTUAL CROSSMATCH??? WE ARE DOING IT NOW! (BUT NOT WELL…)

  12. WHAT IS A VIRTUAL CROSSMATCH? • Recipient antibodies fully characterized, known, and computerized (i.e., UNOS “unacceptable/avoid” algorithm) • Recipients with antibody to donor antigens are eliminated without crossmatch • parameters for which antibodies important determined at local level • Not a substitute for final crossmatch for remaining potential recipients

  13. FINAL XM WORKLOADCURRENT PRACTICE • Regional trays by ABO blood group • (First phase XMs – 100s of samples) • Final XMs • Negative patients from first phase with highest number of points (may be up to 25) • Highly sensitized patients often positive in final XM done by more sensitive technique (e.g., Flow) – i.e., wasted effort

  14. CALCULATED PRA –STANDARDIZED

  15. VIRTUAL XMPROPOSED PRACTICE • No first phase testing • Final XMs • Incompatible recipients excluded by computer • Select top 5 – 10 patients on match run for final XM • Highly sensitized patients likely to be transplanted

  16. First phase XMs 3-4 hrs Final XMs – >25 Repeat CDC Flow Highly sensitized patients eliminated at final – wasted effort First phase XMs 3-4 hrs Final XMs - 5 Repeat CDC Flow Highly sensitized patients transplanted Crossmatch Comparison

  17. VIRTUAL CROSSMATCH • CHALLENGES • Requires complete and accurate knowledge of historical and current antibody specificity/isotype by most sensitive methods • Requires real time updating of “unacceptables” in UNET • Requires regular screening (not less than quarterly) – More for desensitization protocols

  18. VIRTUAL CROSSMATCH • CHALLENGES cont’d • Antibody profiles can change over time (e.g., become weaker) • Desensitization protocols can cause real time variation in antibody profile • May eliminate an eligible recipient depending on local preference (e.g., patient with antibody to 50% of the A2+ cells on panel)

  19. VIRTUAL CROSSMATCH BENEFITS Decreases numberof patients needing actual final crossmatch (No regional screen trays) Decreases timerequired for final crossmatching Minimizeswasted time crossmatching highly sensitized patients with known incompatibilities Decrease in CITin some regions Accelerates organ placement

  20. CONCLUSIONS VIRTUAL PRA • Results in National PRA Equivalence VIRTUAL CROSSMATCH • Accelerates organ placement

  21. CAVEATA variant systemis requiredfor patientsundergoing desensitization

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