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Improving the performance of virtual crossmatch results by correlating with nationally-performed physical
Sean M Wrenn1, Carlos E Marroquin1, Donna-Sue Hain2
1University of Vermont Robert Larner, M.D. College of Medicine, Department of Transplant Surgery, Burlington, VT, United States.
Insights
Local mean fluorescence intensity (MFI) results for donor-specific HLA antibodies (DSA) can predict crossmatch outcomes. This study establishes a reliable model for predicting positive or negative crossmatches based on DSA MFI values in proficiency testing.
Area of Science:
- Transplantation immunology
- Clinical diagnostics
- Immunogenetics
Background:
- Donor-specific HLA antibodies (DSA) are critical in solid organ transplantation.
- Predicting crossmatch outcomes based on DSA reactivity strength (mean fluorescence intensity, MFI) remains challenging.
Purpose of the Study:
- To evaluate the predictive value of locally generated DSA MFI for crossmatch results.
- To compare local MFI data with national proficiency testing outcomes.
Main Methods:
- DSA MFI from single antigen beads were analyzed for proficiency testing samples (2011-2015).
- Local MFI data was compared against aggregate positive crossmatch percentages from other laboratories.
- Crossmatch methods included direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), and flow cytometry.
Main Results:
- Positive CDC-AHG and flow crossmatches correlated with specific MFI thresholds for HLA class I and II.
- Low MFI (<3000) demonstrated high positive predictive values for negative crossmatches.
- High MFI (>8000) showed high negative predictive values for positive crossmatches.
Conclusions:
- Locally generated MFI results from proficiency testing reliably predict crossmatch outcomes.
- This provides a replicable model for transplant centers to interpret DSA MFI.
- Standardizing MFI interpretation enhances transplant safety and efficacy.
Purpose:
When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch.
Method:
DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015.
Results:
180 surveys were analyzed. Positive CDC-AHG and flow cytometric crossmatches were associated with MFI greater than 8554 and 2748 respectively for HLA class I, and 6919 and 3707 respectively for class II. Institutional MFI less than 3000 had high positive predictive values (0.98, 0.85, 0.81) for negative direct, AHG, and flow crossmatches, while MFI greater than 8000 had high negative predictive values for a positive direct, AHG, and flow crossmatches (1.00, 1.00, 0.97).
Conclusion:
Review of locally-generated MFI results as part of participating in proficiency testing allow for predictability of crossmatch results against other laboratories, providing a replicable model for other participating centers.
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