Antibody Therapeutics as Interfering Agents in Flow Cytometry Crossmatch for Organ Transplantation

Background: Daratumumab is a human monoclonal antibody targeting CD38 used widely in various related conditions. Caution is advised when interpreting the pretransfusion tests in daratumumab-treated patients because they may show nonspecific reactions with red blood cells. This paper provides experimental evidence for the false-positive interference phenomena induced by daratumumab in in-vitro and ex-vivo experiments and experimental support for resolving it using dithiothreitol (DTT). Methods: Fifteen crossmatching pairs, four cardiac amyloidosis (CA) patients treated with daratumumab, and three healthy individuals were included. The flow cytometry crossmatch (FCMXM) was conducted with negatively selected T and B cells. After spiking the sera with 500 μg/mL daratumumab, the T and B cells were treated with DTT. The prospective FCMXM was conducted with the sera of CA patients treated with daratumumab. The CD38 expression levels in T, B, and NK cells were measured without and with a DTT or pronase treatment. Results: Five hundred μg/mL of daratumumab spiking was sufficient to elicit a false positive effect in T cell FCMXM. In particular, the administration of 0.1 M DTT efficiently resolved the induced false positivity in flow cytometry. Moreover, DTT caused a decrease in the CD38 expression levels in T, B, and NK cells. Conclusion: A typical therapeutic dose of daratumumab causes false-positive FCMXM, which was effectively addressed by a DTT treatment. Therefore, information about the patient's medical condition and the use of immunotherapeutics, such as daratumumab, is needed, given its impact on diverse CD38-expressing cells. (Korean

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The Interplay Between Human Leukocyte Antigen Antibody Profile and COVID-19 Vaccination in Waitlisted Renal Transplant Patients

Zhao,

Kakodkar,

Pan

et al. 2024

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti–human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned. Objective.— To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile. Design.— A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers. Results.— There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history. Conclusions.— Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.

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Antibody Therapeutics as Interfering Agents in Flow Cytometry Crossmatch for Organ Transplantation

Cited by 3 publications

References 41 publications

Applications of Flow Cytometry in Transplant Medicine

Applications of Flow Cytometry in Transplant Medicine

Daratumumab-Induced Interference in Flow-Cytometry Crossmatch and Resolving It by DTT Treatment

The Interplay Between Human Leukocyte Antigen Antibody Profile and COVID-19 Vaccination in Waitlisted Renal Transplant Patients

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