Microscopic Polyangiitis-related Pulmonary Fibrosis
Autoimmune pulmonary alveolar proteinosis (aPAP), which causes 90% of all PAP cases, is an autoimmune disease caused by the presence of an autoantibody against granulocyte-macrophage colony stimulating factor (GM-CSF). The suppression of GM-CSF signaling by anti-GM-CSF autoantibody disrupts the surfactant catabolism, resulting in the accumulation of surfactant lipids and proteins in pulmonary alveolar macrophages and alveoli. The clinical course of aPAP is variable. In the contemporaneous cohort of 223 Japanese aPAP patients, 3 patients (1.4%) were complicated by severe respiratory failure due to pulmonary fibrosis. And so far, there have been, at least, 5 case reports, which highly suggested the pathogenetic relationship between aPAP and pulmonary fibrosis.
The pathogenesis of pulmonary fibrosis in aPAP is unknown. It has been hypothesized that the retention of lipoproteinaceous material in the alveoli, silica exposure, and/or superimposed pulmonary infections induces damage to cells lining the alveoli and causes pulmonary fibrosis in aPAP patients. In rats, the overexpression of GM-CSF in the lung by adenovirus-vector leads to pulmonary fibrosis, suggesting an inconclusive relationship between GM-CSF therapy and pulmonary fibrosis in patients with aPAP.
Anti-neutrophil cytoplasmic antibody (ANCA) is a sensitive and specific marker for ANCA-associated systemic vasculitis, as observed in granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), "idiopathic" necrotizing crescentic glomerulonephritis and allergic granulomatous angiitis. In vitro and in vivo studies provide compelling evidence that ANCA play a critical role in the pathogenesis of ANCA-associated systemic vasculitis. Pulmonary fibrosis due to alveolar capillaritis is a common complication in ANCA-associated systemic vasculitis. However, ANCA-related pulmonary fibrosis has never been reported in association with aPAP.
Background
Autoimmune pulmonary alveolar proteinosis (aPAP), which causes 90% of all PAP cases, is an autoimmune disease caused by the presence of an autoantibody against granulocyte-macrophage colony stimulating factor (GM-CSF). The suppression of GM-CSF signaling by anti-GM-CSF autoantibody disrupts the surfactant catabolism, resulting in the accumulation of surfactant lipids and proteins in pulmonary alveolar macrophages and alveoli. The clinical course of aPAP is variable. In the contemporaneous cohort of 223 Japanese aPAP patients, 3 patients (1.4%) were complicated by severe respiratory failure due to pulmonary fibrosis. And so far, there have been, at least, 5 case reports, which highly suggested the pathogenetic relationship between aPAP and pulmonary fibrosis.
The pathogenesis of pulmonary fibrosis in aPAP is unknown. It has been hypothesized that the retention of lipoproteinaceous material in the alveoli, silica exposure, and/or superimposed pulmonary infections induces damage to cells lining the alveoli and causes pulmonary fibrosis in aPAP patients. In rats, the overexpression of GM-CSF in the lung by adenovirus-vector leads to pulmonary fibrosis, suggesting an inconclusive relationship between GM-CSF therapy and pulmonary fibrosis in patients with aPAP.
Anti-neutrophil cytoplasmic antibody (ANCA) is a sensitive and specific marker for ANCA-associated systemic vasculitis, as observed in granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), "idiopathic" necrotizing crescentic glomerulonephritis and allergic granulomatous angiitis. In vitro and in vivo studies provide compelling evidence that ANCA play a critical role in the pathogenesis of ANCA-associated systemic vasculitis. Pulmonary fibrosis due to alveolar capillaritis is a common complication in ANCA-associated systemic vasculitis. However, ANCA-related pulmonary fibrosis has never been reported in association with aPAP.
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