# Evaluation of alternative complement activity within an ARDS cohort

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $124,139

## Abstract

Project Summary: The complement pathway, particularly the alternative complement (AP) pathway, is an
ancient immune surveillance system developed as a mechanism to eliminate pathogen or cellular debris before
the development of specific immune responses. This pathway has ‘built-in’ regulators of its own activation that
prevent collateral tissue damage, and the imbalance of the positive and negative arms of the pathway may result
in collateral tissue damage during profound illness. The goal of this application is to utilize the existing
biospecimen collection that are stored in the NHLBI Biologic Specimen Repository and test whether alternative
complement pathway (AP) activity and key components of the alternative pathway predict overall survival in
patients with ARDS. We propose to use serum samples available from subjects enrolled in the Lisofylline for
ALI/ARDS trial (LARMA) study to determine AP activity and explore the balance of complement factor B (CFB)
an essential proximal mediator of AP activation, and CFH, a negative regulator of AP activation, levels. We also
propose to use plasma samples from subjects enrolled in the Statins for Acutely Injured Lungs from Sepsis trial
(SAILS) to assess the balance of CFB and CFH levels and association with inflammation and mortality. Our
preliminary data from a single center cohort of critically ill mechanically ventilated patients with acute respiratory
failure show that higher AP activity, but not classical complement pathway activity, is associated with reduced
all-cause mortality. Enhanced AP function is associated with reduced risk of bloodstream infection, and serum
from individuals with enhanced AP function show ability to substantially inhibit extensively-drug resistant
carbepenemase-producing Klebsiella pneumoniae growth in vitro. Moreover, increased AP function is
associated with higher CFB and CFH levels and both higher CFB and CFH levels predict enhanced survival.
The major hypothesis is that alternative pathway activity (AH50) and key components of AP predict overall
survival in patients with ARDS from two multi-center, randomized, prospective trials available through BioLINCC.
Aim 1 will test the association between AP activity, CFB and CFH levels, and risk of 28-day mortality in patients
enrolled in LARMA. As secondary endpoints, we will test the relationship between AP activity and ventilator-free
days, organ failure-free days for the five non-pulmonary organs examined in the original LARMA study. Aim 2
will identify whether CFB and CFH levels predict mortality in a cohort with sepsis-associated acute lung injury.
As secondary endpoints, we will examine the relationship between CFB, CFH levels and ventilator-free days,
organ-failure free days, and systemic inflammation as measured by C-reactive protein in the original SAILS
cohort. Understanding the balance of immune activation and regulatory factors is an important step toward
design of future clinical trials and successful completion...

## Key facts

- **NIH application ID:** 10038565
- **Project number:** 1R21HL148088-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Janet Sojung Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,139
- **Award type:** 1
- **Project period:** 2020-08-09 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038565

## Citation

> US National Institutes of Health, RePORTER application 10038565, Evaluation of alternative complement activity within an ARDS cohort (1R21HL148088-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038565. Licensed CC0.

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