Biomarkers Predict Relapse in Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed, up to date no satisfactory biomarker has been identified that can reliably predict relapse. This study assessed the probability of the occurrence of a relapse when a change was noted in a range of commonly used laboratory tests. These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies, ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of 66 relapse episodes was investigated and a novel clinical yield score was devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count was observed in the 6-month period before a relapse event, 59% of patient relapses could be predicted. Monitoring changes in this set of parameters helps identify disease relapse. 1. Introduction Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis primarily affecting the respiratory tract and kidneys and is characterised by necrosis and granulomatous lesions involving small to medium sized blood vessels. The principal autoantibody associated with the disease is the antineutrophil cytoplasmic antibody (ANCA), usually directed against the enzyme proteinase-3 (PR3) [1, 2]. Long term survival in GPA has greatly improved since the introduction of disease modifying agents such as cyclophosphamide, with a ten-year survival of approximately 75% [3]. Disease relapse is a major cause of morbidity and mortality in patients with GPA, with some 50% of patients experiencing relapse at five-year followup [4]. Prediction of disease relapse is therefore an important goal of clinical management. Certain patient and disease factors have been identified as increasing the risk of relapse. For example, it has been shown that lung involvement, infection with staphylococcus aureus, and cardiac or renal involvement increase the chance of relapse [5–7]. The identification of biomarkers that predict relapse in GPA has proven elusive. While a change in ANCA titre may be associated with disease activity, it is not sufficiently specific nor sensitive to be an effective predictor of relapse [8] and