HERPUD1 and achalasia-alacrima syndrome: AAAs are marked by a high M1:M2 cell ratio34, suggesting that various inflammatory cytokines secreted by M1 macrophages such as migration inhibitory factor (MIF-1) and tumor necrosis factor (TNF) in addition to matrix metalloproteinases (MMP-9) are responsible for the degradation of ECM proteins in the vessel wall, causing continuous dilatation of the aortic lumen35,36.