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.
John P. Reilly, Nuala J. Meyer, Michael G.S. Shashaty, Brian J. Anderson, Caroline Ittner, Thomas G. Dunn, Brian Lim, Caitlin Forker, Michael P. Bonk, Ethan Kotloff, Rui Feng, Edward Cantu, Nilam S. Mangalmurti, Carolyn S. Calfee, Michael A. Matthay, Carmen Mikacenic, Keith R. Walley, James Russell, David C. Christiani, Mark M. Wurfel, Paul N. Lanken, Muredach P. Reilly, Jason D. Christie
Title and authors | Publication | Year |
---|---|---|
The ultimate tradeoff: how red cell adaptations to malaria alter the host response during critical illness
Dobkin J, Wu L, Mangalmurti NS |
AJP Lung Cellular and Molecular Physiology | 2023 |
Erythroprotective Potential of Phycobiliproteins Extracted from Porphyridium cruentum
Peña-Medina RL, Fimbres-Olivarría D, Enríquez-Ocaña LF, Martínez-Córdova LR, Del-Toro-Sánchez CL, López-Elías JA, González-Vega RI |
Metabolites | 2023 |
Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.
Reilly JP, Zhao Z, Shashaty MGS, Koyama T, Jones TK, Anderson BJ, Ittner CA, Dunn T, Miano TA, Oniyide O, Balmes JR, Matthay MA, Calfee CS, Christie JD, Meyer NJ, Ware LB |
Intensive Care Medicine | 2023 |
Aetiology of Community-Acquired Pneumonia and the Role of Genetic Host Factors in Hospitalized Patients in Cyprus.
Ladas P, Porfyridis I, Tryfonos C, Ioannou A, Adamide T, Christodoulou C, Richter J |
Microorganisms | 2023 |
Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis
Meng H, Sengupta A, Ricciotti E, Mrčela A, Mathew D, Mazaleuskaya LL, Ghosh S, Brooks TG, Turner AP, Schanoski AS, Lahens NF, Tan AW, Woolfork A, Grant G, Susztak K, Letizia AG, Sealfon SC, Wherry EJ, Laudanski K, Weljie AM, Meyer NJ, FitzGerald GA |
Clinical and Translational Medicine | 2023 |
ABO Histo-Blood Group and the von Willebrand Factor Axis in Severe COVID-19.
Reilly JP, Shashaty MGS, Miano TA, Giannini HM, Jones TK, Ittner CAG, Christie JD, Meyer NJ |
2023 | |
ABO blood groups and nosocomial infection.
Zhong X, Wang DL, Xiao LH, Mo LF, Luo XF |
Epidemiology and Infection | 2023 |
Involvement of Diverse Populations in Transfusion Medicine Research
Miller YM, Bakhtary S, Chou ST, Hailu B, Reik RA, Richard RH, Spencer BR, Witherspoon R, Delaney M |
Transfusion Medicine Reviews | 2023 |