# The role of type 1 interferon in regulating alloimmune responses to transfused red blood cells

> **NIH NIH K08** · CEDARS-SINAI MEDICAL CENTER · 2021 · $164,052

## Abstract

Abstract:
With approximately 5 million Americans transfused per year, red blood cell (RBC) transfusion is the most
common procedure performed in United States hospitals. RBC transfusion exposes recipients to hundreds of
non-ABO antigens that are not matched between donors and recipients. This exposure can lead to production
of antigen-specific alloantibodies, which can cause potentially fatal hemolytic transfusion reactions and limit
availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Currently, there
are no means to predict which recipients have an elevated risk of alloimmunization. Identification of at-risk
patients would allow for interventions to inhibit alloimmunization and its detrimental effects. Thus, identifying
factors that determine which individuals will develop RBC alloimmune responses has been recognized as a
research priority in transfusion medicine by the NHLBI. One contributing factor is the inflammatory state of the
transfusion recipient. Recent studies have reported an increased frequency of alloimmunization in patients with
disseminated viral infections or inflammatory diseases, including multiple autoimmune diseases. However, the
molecular mechanisms underlying this association, including the role of critical inflammatory cytokines, are
poorly understood. Given that type 1 interferons (IFNα/β) regulate antiviral immunity and autoimmune pathology,
we hypothesize that IFNα/β signaling regulates alloimmune responses to RBC antigens. Preliminary data
indicate that IFNα/β production and signaling, specifically in B cells, is required for alloimmunization in mice.
Using a murine model of transfusion, we aim to identify mechanisms underlying transfusion-induced IFNα/β
production (Aim 1) and B cell responses to IFNα/β signaling during RBC alloimmunization (Aim 2). Findings will
provide a potential mechanistic basis for past observations of inflammation-induced alloimmunization. In
addition, results may identify potential targets of laboratory tests that could improve prediction of
alloimmunization. The candidate is a post-doctoral fellow in Laboratory Medicine. He proposes to gain mentored
research experience and career development training as a physician-scientist in Transfusion Medicine. The
project will provide experience in applying innate immune mechanisms to regulation of RBC alloimmune
responses. Training will be conducted at Yale School of Medicine under the mentorship of leaders in Transfusion
Medicine and innate immunity. The candidate will develop experimental and analytical skills, including
microscopic analysis of lymphoid tissue, quantification of B cell processes in vivo, and acquisition and analysis
of high-throughput RNA sequencing data. He will complete a career development plan that includes coursework
in inflammation, biostatistics, and translational immunology. His career directions will be shaped by his
participation in local and international associations of immuno...

## Key facts

- **NIH application ID:** 10194579
- **Project number:** 5K08HL141446-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** David R Gibb
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,052
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194579

## Citation

> US National Institutes of Health, RePORTER application 10194579, The role of type 1 interferon in regulating alloimmune responses to transfused red blood cells (5K08HL141446-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194579. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*