# An ABO Blood Type Defined ARDS Endotype in Sepsis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $559,387

## Abstract

ABSTRACT
Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome of lung inflammation, alveolar
capillary barrier dysfunction, and micro-thrombosis that is common in sepsis. Mortality is above 30% and no
pharmacotherapies exist for ARDS. We previously identified a reproducible association between ABO blood
type A and an approximately 14% higher absolute risk of ARDS compared to blood type O in sepsis. ABO
blood type is genetically determined by the ABO gene, which encodes a family of glycosyltransferases
responsible for catalyzing specific carbohydrate modifications on glycans and glycoproteins on erythrocytes,
endothelial cells, and platelets. The genetic variation that determines blood type is associated with risk to
multiple coagulopathic diseases, including myocardial infarction and venous thromboembolism, as well as
plasma levels of multiple endothelial-derived glycoproteins. Our published preliminary data, demonstrate an
association between the genetically determined A1 subtype of blood type A, distinguished by 30-50 fold higher
“A” transferase activity relative to the A2 subtype, and highest ARDS risk. Additionally, we identified an
association of blood type with plasma levels of two proteins measured early in sepsis and important in
endothelial activation and coagulation, von Willebrand factor (vWF) and soluble thrombomodulin (sTM), as well
as with risk of disseminated intravascular coagulation (DIC). These same proteins have been implicated in
ARDS. On vWF, A antigens reduce degradation by ADAMTS13, resulting in a pro-coagulant effect, suggesting
septic blood type A patients may require higher ADAMTS13 levels. Therefore, we hypothesize that there is an
endotype of ARDS influenced by ABO blood type that can be identified and targeted clinically. The goals of the
research proposed in this application is to obtain critical information necessary to identify a population most
likely to benefit from therapies targeting ABO-influenced vascular biology and to understand the effect of ABO
glycans on injured lungs. We will accomplish this through the following Aims; Aim 1 will determine the
association of genetically determined ABO blood type A1 and mortality in sepsis and sepsis-associated ARDS,
in two large cohorts of critically ill sepsis patients. Aim 2 will derive and validate a predictive tool that includes
ABO genotype, plasma levels of vWF and sTM, and components of the DIC score to identify a population at
high risk for an ABO-defined coagulopathic endotype of ARDS in sepsis. Aim 3 will determine the longitudinal
physiologic effects of ABO blood type on lung injury recovery in an ex vivo lung perfusion (EVLP) model and
test if these effects are modified by the administration of recombinant ADAMTS13. The multidisciplinary team
of investigators includes a translational scientist and genetics expert (Meyer), two molecular epidemiologist
with expertise in ARDS and predictive modeling (Christie, Ware), an EVLP expert (Cantu), a ...

## Key facts

- **NIH application ID:** 10491982
- **Project number:** 5R01HL155159-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** John Patrick Reilly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $559,387
- **Award type:** 5
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491982

## Citation

> US National Institutes of Health, RePORTER application 10491982, An ABO Blood Type Defined ARDS Endotype in Sepsis (5R01HL155159-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10491982. Licensed CC0.

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