# Cellular and Molecular Determinants of RBC Alloimmunization Responder Status

> **NIH NIH P01** · UNIVERSITY OF VIRGINIA · 2020 · $423,895

## Abstract

Project Summary
RBC alloimmunization represents a major complication of chronic transfusion therapy. For those patients
who are unfortunate enough to generate multiple alloantibodies, provision of compatible antigen negative
RBCs can be both time and resource intensive. In rare cases, this can result in an inability to locate an
otherwise life-saving therapy. Among chronically transfused patients, those with Sickle Cell Disease (SCD)
suffer disproportionately from alloimmunization. This proposal sets out to determine the cellular and
molecular controllers of responder vs. non-responder status in SCD patients. Our overarching hypothesis is
that differential control of T follicular helper cell (TFH) subset differentiation by cytokines is responsible for
alloimmunization responses in general, and for responder vs. non-responder status in SCD patients in
particular. This proposal combines studies of experimentally tractable mouse models of specific cytokine
deficiency with cytokine driven TFH differentiation assay performed on human lymphocytes from both
healthy donors and SCD patients. By providing a molecular mechanism capable of explaining and predicting
responder status among SCD patients, this proposal could have a significant impact on the transfusion care
of SCD patients. Knowing a patient's responder status prior to initiating transfusion therapy would allow for a
more personalized and tailored therapeutic approach. For example, we could determine which patients are
likely to get the most benefit from extended phenotype matching protocols. Ultimately, understanding the
molecular regulators that dictate responder status would also help in the identification of potential targets for
future therapeutic intervention.

## Key facts

- **NIH application ID:** 10018093
- **Project number:** 5P01HL132819-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** CHANCE MARION JOHN LUCKEY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,895
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018093

## Citation

> US National Institutes of Health, RePORTER application 10018093, Cellular and Molecular Determinants of RBC Alloimmunization Responder Status (5P01HL132819-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018093. Licensed CC0.

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