# Project 3 - Mechanisms of DNRAb-mediated damage to the fetal brain

> **NIH NIH P01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $709,832

## Abstract

Project 3:
Abstract
We have shown that antibodies cross-reactive with DNA and the N-methyl D-aspartate receptor
(NMDAR), termed DNRAbs and present in approximately 30% of patients with Systemic Lupus
Erythematosus, can exit the maternal circulation, enter the fetal circulation and the fetal brain
leading to the death of female fetuses and impaired cognition in male offspring. We now
propose to understand the mechanism of DNRAb-mediated brain injury in female and male
fetuses and whether FcR-mediated mechanisms are involved. We will also determine the
contribution of each of the NMDAR subunits, GluN2A and GluN2B, both of which are targets of
DNRAb, to the antibody-mediated damage. Finally, we have demonstrated that some mutations
in the Fc portion of IgG render an antibody unable to cross the placenta and enter the fetal
circulation. We will attach NMDAR subunits or DWEYS peptide to these Fc constructs to create
a decoy antigen that will not cross the placenta in order to develop a strategy to protect the fetus
from maternal DNRAb. This last goal could lead to a generalizable strategy to protect a fetus
from maternal antibody with pathogenic potential.

## Key facts

- **NIH application ID:** 10885148
- **Project number:** 5P01AI073693-15
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Betty Diamond
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $709,832
- **Award type:** 5
- **Project period:** 2008-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885148

## Citation

> US National Institutes of Health, RePORTER application 10885148, Project 3 - Mechanisms of DNRAb-mediated damage to the fetal brain (5P01AI073693-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885148. Licensed CC0.

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