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Can solid phase assays be better utilized to measure efficacy of antibody removal therapies?
Anat R Tambur1, Denis Glotz2, Nancy D Herrera1
1Transplant Immunology Laboratory, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract:
Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum-inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies.
Insights
Titration studies offer a more reliable method for measuring antibody levels during antibody removal therapies. This approach provides a better estimate of treatment response compared to current methods.
Area of Science:
- Immunology
- Transplantation Science
- Clinical Chemistry
Background:
- Antibody removal therapies are crucial for patients with antibody-mediated rejection and for desensitization to enable transplantation.
- Accurate monitoring of antibody levels is essential for guiding treatment decisions and assessing efficacy.
- Current FDA-approved solid-phase assays for HLA antibody identification are not considered reliable surrogates for treatment efficacy.
Purpose of the Study:
- To evaluate the efficacy of titration studies in monitoring antibody levels during antibody removal therapies.
- To compare the accuracy and reliability of titration studies against IgG and C1q single-antigen-bead assays.
- To determine if titration studies can serve as a companion diagnostic for monitoring treatment effectiveness.
Main Methods:
- Serum samples from 40 patients undergoing antibody removal therapies were analyzed using paired pre- and post-treatment samples (58 assays).
- Mean Fluorescence Intensity (MFI) values from IgG and C1q single-antigen-bead assays were compared with antibody titer values obtained through serial dilutions.
- Antibody reduction was calculated as the delta-reduction of antibody levels from pre- to post-treatment.
Main Results:
- Titration studies mitigated serum-inherent inhibitory factors and over-saturation limitations, providing a better estimation of antibody-binding strength.
- Delta-reduction values from titration studies demonstrated significantly greater uniformity compared to IgG or C1q assays.
- Analyzing results based solely on C1q positivity or high MFI values did not alter the overall magnitude of the findings.
Conclusions:
- Titration studies offer a more robust and reliable method for estimating antibody levels and assessing responsiveness to antibody removal therapies.
- This method provides a more uniform and accurate measure of antibody reduction compared to current solid-phase assays.
- Titration studies show promise as a companion diagnostic tool for monitoring the efficacy of antibody removal treatments.
