Indeed, compensatory immune-inflammatory responses to UCB have been proposed in patients with bilirubin encephalopathy, where certain bioactive proteins, including defensins (e.g. α- defensin 1, DEFA1) and/or alarmins (e.g. C−reactive protein, S100A7 or S100A9) were differentially up/-down-regulated in extracellular vesicles isolated from the cerebrospinal fluid of those patients (Tan et al., 2020). This evidence concerns the gene DEFA1 and bilirubin encephalopathy.