# Using B cell features to explain heterogeneity in the rate of T1D progression

> **NIH NIH R03** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $174,100

## Abstract

Project Summary / Abstract
The overall goal for this Gateway Award is to evaluate B cell endotypes and examine how an endotype may be
associated with T1D progression in autoantibody-positive individuals. Importantly, this award will provide an
opportunity for the PI, as an Early Stage Investigator, to formally collaborate with Type 1 Diabetes TrialNet.
The natural history of T1D is well understood, progressing from genetic risk, to autoimmunity, to clinical disease,
and then to further ongoing loss of beta cell function. However, each step of this progression, as well as response
to disease modifying immune therapy, is characterized by considerable heterogeneity. Much of our own work
has aimed to identify immune markers that explain this heterogeneity; we recently showed that more rapid
disease progression after diagnosis was evident in younger subjects with an increased B cell signature, and that
this same signature predicted response to a B-cell targeting drug. Together, these findings suggest that B cells
play an important role in some individuals with T1D. We propose that B cell characteristics may identify an
endotype, or underlying disease mechanism of T1D that may be selectively targeted therapeutically, and that
this can be seen in at-risk individuals as it was in the new onset setting.
Despite these findings, there remain significant gaps in knowledge. First, can B cell endotypes observed after
diagnosis explain heterogeneity in rate of progression from antibody positivity to clinical T1D? It is also unknown
whether B cell endotypes are fixed characteristics of individuals or change as disease changes. Finally, it is likely
that as-yet unidentified subpopulations of B cells, rather than the total population, mechanistically explain these
findings. To address these gaps, we propose to address the hypothesis that B cell levels and signatures
constitute a stable endotype prior to clinical diagnosis of T1D which will be associated with progression to T1D
in the subset of subjects bearing this endotype.

## Key facts

- **NIH application ID:** 10133379
- **Project number:** 1R03DK127475-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Cate Speake
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,100
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133379

## Citation

> US National Institutes of Health, RePORTER application 10133379, Using B cell features to explain heterogeneity in the rate of T1D progression (1R03DK127475-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133379. Licensed CC0.

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