The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Abstract

Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid-phase single-antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring, and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions.

Donor‐specific antibodies in a pediatric kidney transplant population—Prevalence and association with antiproliferative drug dosing

“…Class II DSA formation had a higher prevalence than class I formation, 19.4% vs 9%, respectively, with 17.9% of patients demonstrating what we deemed clinically significant (MFI > 2000) class II DSA titers, fully recognizing that MFI readings can be misleading as described by Sullivan et al Class II DSAs are more notorious for being difficult to treat, and their presence is predictive of graft dysfunction even before other changes, such as diminished renal function, become apparent …”

“…10,14 Strategies to avoid this increased immunological risk could include MMF dose adjustments guided by therapeutic drug monitoring, 15 conversion to enteric-coated mycophenolate mofetil, or even conversion to adequate doses of MMF's "predecessor" azathioprine, especially when these antiproliferative agents are used in conjunction with tacrolimus and at later time points after transplantation when the advantages of MMF over azathioprine are less clear. 15,16 Class II DSA formation had a higher prevalence than class I formation, 19.4% vs 9%, respectively, with 17.9% of patients demonstrating what we deemed clinically significant (MFI > 2000) class II DSA titers, fully recognizing that MFI readings can be misleading as described by Sullivan et al 17 Class II DSAs are more notorious for being difficult to treat, and their presence is predictive of graft dysfunction even before other changes, such as diminished renal function, become apparent. 18 In our study, a reduced eGFR (mL/min/1.73 m 2 ) was observed in patients with DSA formation.…”

Results of early treatment for de novo donor‐specific antibodies in pediatric kidney transplant recipients in a cross‐sectional and longitudinal cohort

“…MFI, C1q reactivity and antibody titration trends over time are being used as a measure of treatment efficacy. Reliance on MFI alone is questionable in accuracy as Luminex SAB technology was not designed as a quantitative test, but in the absence of a more reliable tool, it has become the common practice across many centers . Antibody titration employed by our center provides additional information on antibody burden and should be considered in the assessment of dnDSA strength .…”

Out with the old, in with the new: Virtual versus physical crossmatching in the modern era

“…Note that DSA designation is given without indicating specific MFI thresholds. This was done purposefully because of the complex nature of MFI interpretation . MFI thresholds are, for the most part, center‐specific.…”

“…This was done purposefully because of the complex nature of MFI interpretation. 71 MFI thresholds are, for the most part, center-specific. As such, variability in MFI thresholds can be attributed to a center's testing protocols, technologist's experience, and local clinical practice.…”