ABO Blood Type: a window into the genetics of acute respiratory distress syndrome susceptibility.

Rizzo, Alicia N; Schmidt, Eric P

The genetic factors that determine a patient's risk for developing the acute respiratory distress syndrome (ARDS) remain understudied. In this issue of the JCI, Reilly and colleagues analyzed three cohorts of critically-ill patients and observed an association between the ABO allele A1 and the onset of moderate-severe ARDS. This association was most notable in patients with non-pulmonary sepsis (an indirect, vascular-targeted mechanism of lung injury) and persisted in patients who lacked epithelial expression of the A antigen, suggesting an endothelial mechanism of A1-associated ARDS susceptibility. Critically-ill patients with blood type A had increased circulating concentrations of endothelial-derived glycoproteins von Willebrand Factor and soluble thrombomodulin, and marginal lungs from blood type A donors were less likely to recover function during ex vivo perfusion. These findings implicate A antigen glycosylation of endothelial cells as a critical, genetically-determined risk factor for indirect lung injury that may contribute to the mechanistic heterogeneity of ARDS.