AGER and acute respiratory distress syndrome: In addition, circulating RAGE soluble isoforms are modified differentially in patients with ARDS, with decreased levels of esRAGE (produced through alternate splicing [43]) and increased sRAGE, mainly through mRAGE cleavage by upregulated matrix metalloproteinases [9, 44], thus illustrating the complexity of the regulation of the RAGE pathway during acute illness.