# Characterization of Naturally Occurring Anti-Blood Group Antibody Formation

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $11,562

## Abstract

PROJECT SUMMARY
Despite the discovery of ABO(H) blood group antigens and corresponding anti-ABO(H) antibodies over a
century ago, anti-ABO(H) antibodies remain one of the most significant immunological barriers to transfusion
and transplantation. Moreover, the mechanisms responsible for anti-blood group antibody formation and its
regulation remain relatively unknown. Previous studies suggest that exposure to microbes expressing
membrane carbohydrate structures resembling ABO(H) antigens may be a driving force in the formation of
naturally occurring anti-ABO(H) blood group antibodies. In order to examine the role of blood group expressing
microbe exposure in the development of anti-blood group antibody formation, we generated a novel animal
model that lacks the mouse blood group B disaccharide (Bdis), generating a recipient that is analogous to
human blood group O individuals. Preliminary studies indicate that Bdis negative recipients housed in standard
conditions readily produce anti-Bdis antibodies at high titers, while those housed in specific pathogen free (SPF)
conditions are unable to produce anti-Bdis antibodies until exposed to Bdis positive microbes in adulthood.
Taken together, these findings suggest that microbial exposure may be required for naturally occurring anti-Bdis
antibody development. Additional preliminary data demonstrate that exposure to microbes at a younger age
results in a greater magnitude of antibody production. However, these high antibody titers fail to persist at
constant levels among recipients, which may mirror alterations in sustained colonization of Bdis positive
bacteria. These results parallel clinical observations regarding significant differences in anti-ABO(H) antibodies
between individuals. Given this variability in antibody levels across age groups and housing conditions of the
Bdis negative model, we hypothesize that the timing and duration of microbial exposure impacts the
magnitude and persistence of anti-blood group antibody production. To test this hypothesis, we propose
the following specific aims: Aim 1. Define the impact of recipient age on the development of anti-Bdis
antibodies relevant in anti-ABO(H) hemolytic transfusion reactions. Aim 2. Define the requirement of continued
microbial exposure for the persistent production of anti-Bdis antibody relevant to hemolytic transfusion
reactions. These studies will provide novel insight into the role blood group expressing microbes play in the
production and persistence of anti-ABO(H) antibodies, the most common immunological barrier to
transplantation and transfusion therapy.

## Key facts

- **NIH application ID:** 10223410
- **Project number:** 5F31HL138934-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Nourine Ahmed Kamili
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $11,562
- **Award type:** 5
- **Project period:** 2017-07-31 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223410

## Citation

> US National Institutes of Health, RePORTER application 10223410, Characterization of Naturally Occurring Anti-Blood Group Antibody Formation (5F31HL138934-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10223410. Licensed CC0.

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