# Uncovering the Impact of Innate Immunity on Transfusion Medicine Immunobiology

> **NIH NIH K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $172,800

## Abstract

Summary: While anti-ABO(H) antibodies represent the most common immunological barrier to transfusion and
transplantation, variation in anti-ABO(H) antibody levels and overall specificity may play a critical role in dictating
the clinical consequence of these naturally occurring antibodies on adverse events following ABO(H)
incompatible transfusion and transplantation. However, the factors that regulate this variation, and development
of anti-ABO(H) antibodies in general, remain relatively unknown. Given this, our long-term goal is to define key
factors that regulate the production and clinical outcome of naturally occurring anti-ABO(H) antibodies. Our
central hypothesis is that innate immune factors target blood group expressing microbes, which shapes the
specificity and clinical significance of naturally occurring anti-ABO(H) blood group antibodies. Our results also
demonstrate that a series of innate immune lectins called galectins possess the ability to specifically bind and
kill blood group positive (BG+) microbes through engagement of their carbohydrate BG antigens. Using a new
preclinical model that leverages the murine equivalent of ABO(H) blood group antigens, we have also shown
that these same microbes can drive the formation of anti-BG antibodies capable of causing ABO(H) incompatible
hemolytic transfusion reactions (HTRs). Microbial populations within galectin knockout strains demonstrate
significantly increased numbers of BG+ microbes and exposure of recipients to the non-metabolizable pan
galectin inhibitor, thiodigalactoside (TDG), likewise results in increased colonization by BG+ microbes. However,
galectin absence or inhibition blunts the ability of BG+ microbes to stimulate anti-blood group antibody formation,
suggesting that galectin-mediated microbial killing enhances anti-blood group antibody formation. Importantly,
we have also shown that galectins do not target all BG+ microbes equally. Thus, a dynamic interplay between
the composition of distinct blood group positive microbes in an individual’s microbiota and the ability of galectins
to target these microbes exists that may ultimately shape the specificity and overall levels of anti-BG antibodies.
As studies to address this intriguing possibility require a unique combination of expertise, I will leverage my
current expertise in glycobiology and microbiology with key training in immunology and transfusion medicine,
obtained during the K99 phase of this proposal. I will also leverage our new preclinical model and series of
recently developed glycan microarrays and build on these tools with establishment of key galectin KO lines and
continued microarray expansion to address the following specific aims. Aim 1: Define the role of galectins in
shaping anti-blood group antibody levels. Aim 2: Define the consequence of anti-blood group antibody
repertoire on HTRs. Completion of these aims will provide unprecedented insight into the fundamental and
previously unrecognized role of th...

## Key facts

- **NIH application ID:** 10887049
- **Project number:** 1K99HL169746-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shang-Chuen Wu
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $172,800
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887049

## Citation

> US National Institutes of Health, RePORTER application 10887049, Uncovering the Impact of Innate Immunity on Transfusion Medicine Immunobiology (1K99HL169746-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10887049. Licensed CC0.

---

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