Microscopic Polyangiitis - Cause

Cause

While the mechanism of disease has yet to be fully elucidated, the leading hypothesis is that the process is begun with an autoimmune process of unknown etiology that triggers production of p-ANCA. These antibodies will circulate at low levels until a pro-inflammatory trigger — such as infection, malignancy, or drug therapy. The trigger upregulates production of p-ANCA. Then, the large number of antibodies make it more likely that they will bind a neutrophil. Once bound, the neutrophil degranulates. The degranulation releases toxins that cause endothelial injury. Most recently, two different groups of investigators have demonstrated that anti-MPO antibodies alone can cause necrotizing and crescentic glomerulonephritis.