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Citations to this article

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis
V. Eric Kerchberger, … , Edward D. Siew, Lorraine B. Ware
V. Eric Kerchberger, … , Edward D. Siew, Lorraine B. Ware
Published October 1, 2019
Citation Information: JCI Insight. 2019;4(21):e131206. https://doi.org/10.1172/jci.insight.131206.
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Research Article Genetics Pulmonology Article has an altmetric score of 1

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis

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Abstract

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical and environmental risk factors exist, not all patients with risk factors develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported that circulating cell-free hemoglobin (CFH) is elevated during sepsis, and higher levels predict worse outcomes. Excess CFH is rapidly scavenged by haptoglobin (Hp). A common HP genetic variant, HP2, is unique to humans and is common in many populations worldwide. HP2 haptoglobin has reduced ability to inhibit CFH-mediated inflammation and oxidative stress compared with the alternative HP1. We hypothesized that HP2 increases ARDS susceptibility during sepsis when plasma CFH levels are elevated. In a murine model of sepsis with elevated CFH, transgenic mice homozygous for Hp2 had increased lung inflammation, pulmonary vascular permeability, lung apoptosis, and mortality compared with wild-type mice. We then tested the clinical relevance of our findings in 496 septic critically ill adults, finding that HP2 increased ARDS susceptibility after controlling for clinical risk factors and plasma CFH. These observations identify HP2 as a potentially novel genetic ARDS risk factor during sepsis and may have important implications in the study and treatment of ARDS.

Authors

V. Eric Kerchberger, Julie A. Bastarache, Ciara M. Shaver, Hiromasa Nagata, J. Brennan McNeil, Stuart R. Landstreet, Nathan D. Putz, Wen-Kuang Yu, Jordan Jesse, Nancy E. Wickersham, Tatiana N. Sidorova, David R. Janz, Chirag R. Parikh, Edward D. Siew, Lorraine B. Ware

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 5 6 5 6 4 2 28
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2021 (4)

Title and authors Publication Year
Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and non-pulmonary organ dysfunction
JE Meegan, JA Bastarache, LB Ware
American journal of physiology. Lung cellular and molecular physiology 2021
Cell-free hemoglobin-mediated human lung microvascular endothelial barrier dysfunction is not mediated by cell death
T Tomasek, LB Ware, JA Bastarache, JE Meegan
Biochemical and Biophysical Research Communications 2021
Advancing precision medicine for acute respiratory distress syndrome
JR Beitler, BT Thompson, RM Baron, JA Bastarache, LC Denlinger, L Esserman, MN Gong, LM LaVange, RJ Lewis, JC Marshall, TR Martin, DF McAuley, NJ Meyer, M Moss, LA Reineck, E Rubin, EP Schmidt, TJ Standiford, LB Ware, HR Wong, NR Aggarwal, CS Calfee
The lancet. Respiratory medicine 2021
A two-hit model of sepsis plus hyperoxia causes lung permeability and inflammation
Bastarache JA, Smith K, Jesse JJ, Putz ND, Meegan JE, Bogart AM, Schaaf K, Ghosh S, Shaver CM, Ware LB
American Journal of Physiology - Lung Cellular and Molecular Physiology 2021

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