ANCA-Associated Vasculitides and Hematologic Malignancies: Lessons from the Past and Future Perspectives

Figure 1

PR3 biological roles in healthy status and diseases. Center (yellow): the myeloid precursor, promyelocyte, expresses a great amount of PR3 on its surface under G-SCF stimulus, and it is believed that PR3 is able to enhance the proliferation rate of those cell lines in the bone marrow. Homeostasis (green): PR3 allows destruction of phagocytosed bacteria in activated polymorphonuclear cells; moreover, PR3 can interact with apoptotic cells and microvesicle binding phosphatidylserine on the cell surface. PR3 favours diapedesis and works as a modulator of inflammation. AVV (red): PR3 is the main autoantigen in GPA and MPA. It may favour inflammation by interfering with apoptosis or leading to endothelial damage because of ANCA generation that is proved to be enhanced under leukocyte activation, especially neutrophil NETosis. Leukemia (blue): PR3 does not downregulate in leukemia. PR1-specific CTLs and anti-PR1-HLA-A2 are being developed against AML blasts. A PR1 peptide vaccination has already been experimented with success in humans. Abb.: APA: anti-PR1/HLA-A2 antibodies; PV: PR1 peptide vaccination; eCTL: cytotoxic lymphocyte; MB: myeloid blast; PR1/HLA-A2: PR1 peptide being presented by HLA-A2; mPR3: membrane proteinase 3; PB: phagocytosed bacterium; sPR3: soluble proteinase 3; ProM: promyelocyte; resting PMN: resting polymorphonuclear cell; activated PMN: activated polymorphonuclear cell; ANCA: anti-neutrophil cytoplasmic antibodies; Et: endothelium; NETs: neutrophil extracellular traps.