The ABO histo-blood group, endothelial activation, and acute respiratory distress syndrome risk in critical illness
| Autor: | Keith R. Walley, Brian Lim, Caitlin M. Forker, Thomas G. Dunn, Caroline A. G. Ittner, Michael Bonk, Carolyn S. Calfee, Carmen Mikacenic, Paul N. Lanken, Muredach P. Reilly, John P. Reilly, Edward Cantu, Rui Feng, James A. Russell, Michael A. Matthay, Ethan D. Kotloff, Mark M. Wurfel, Nilam S. Mangalmurti, Nuala J. Meyer, David C. Christiani, Jason D. Christie, Michael G.S. Shashaty, Brian J. Anderson |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty ARDS Critical Illness Lung injury Gastroenterology ABO Blood-Group System Sepsis Endothelial activation 03 medical and health sciences 0302 clinical medicine Von Willebrand factor Risk Factors ABO blood group system Internal medicine von Willebrand Factor medicine Humans Aged Blood type Disseminated intravascular coagulation Respiratory Distress Syndrome biology business.industry Endothelial Cells Lung Injury General Medicine Middle Aged medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Commentary biology.protein Wounds and Injuries Female Endothelium Vascular Clinical Medicine business |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci139700 |
| Popis: | BACKGROUND: The ABO histo-blood group is defined by carbohydrate modifications and is associated with risk for multiple diseases, including acute respiratory distress syndrome (ARDS). We hypothesized that genetically determined blood subtype A1 is associated with increased risk of ARDS and markers of microvascular dysfunction and coagulation. METHODS: We conducted analyses in 3 cohorts of critically ill trauma and sepsis patients (n = 3710) genotyped on genome-wide platforms to determine the association of the A1 blood type genotype with ARDS risk. We subsequently determined whether associations were present in FUT2-defined nonsecretors who lack ABO antigens on epithelium, but not endothelium. In a patient subgroup, we determined the associations of blood type with plasma levels of endothelial glycoproteins and disseminated intravascular coagulation (DIC). Lastly, we tested whether blood type A was associated with less donor lung injury recovery during human ex vivo lung perfusion (EVLP). RESULTS: The A1 genotype was associated with a higher risk of moderate to severe ARDS relative to type O in all 3 populations. In sepsis, this relationship was strongest in nonpulmonary infections. The association persisted in nonsecretors, suggesting a vascular mechanism. The A1 genotype was also associated with higher DIC risk as well as concentrations of thrombomodulin and von Willebrand factor, which in turn were associated with ARDS risk. Blood type A was also associated with less lung injury recovery during EVLP. CONCLUSION: We identified a replicable association between ABO blood type A1 and risk of ARDS among the critically ill, possibly mediated through microvascular dysfunction and coagulation. FUNDING: NIH HL122075, HL125723, HL137006, HL137915, DK097307, HL115354, HL101779, and the University of Pennsylvania McCabe Fund Fellowship Award. |
| Databáze: | OpenAIRE |
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