POS0829 SPECTRUM OF ANCA-SPECIFICITIES IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS IN A RETROSPECTIVE MULTICENTER STUDY

Abstract

BackgroundAnti-neutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCA) are found in 10-70% of the patients with eosinophilic granulomatosis with polyangiitis (EGPA) depending on disease activity, methodological aspects and cohort examined [1-3]. Recently, a higher prevalence of anti-pentraxin 3 (PTX3)-ANCA has been reported in EGPA compared to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) [4].ObjectivesTo investigate the spectrum of ANCA specificities in a multicenter cohort of patients with EGPA and identify novel ANCA antigens.MethodsWe conducted a retrospective analysis of 73 patients with EGPA treated between 2015 and 2020 in 3 tertiary referral centers. In addition to in-house ANCA testing with indirect immunofluorescence (IFT) on fixed human granulocytes and antigen-specific enzyme-linked immunosorbent assays (ELISA), ANCA specificities were determined using a cell-based assay (CBA; Euroimmun, Lübeck, Germany). Diagnosis was based on Chapel Hill consensus conference definitions, ACR- and MIRRA-criteria for EGPA. Patient characteristics and clinical manifestations were evaluated and compared based on ANCA status. Fisher`s exact test was employed for comparison of patient groups.ResultsANCA findings are summarized in Table 1. MPO- and proteinase 3 (PR3)-ANCA positive patients (13.7%) had a higher prevalence of peripheral neuropathy (70% vs. 44.4%, p = 0.0003) and glomerulonephritis (20% vs. 14.3%, not significant). MPO- and PR3-ANCA-negative patients (86.3%) had a higher prevalence of heart (10% vs. 46%, p <0.0001), central nervous system (CNS) (0% vs. 14.3%, p <0.0001) and gastrointestinal (10% vs. 22.2%, p = 0.0327) involvement. PTX3-ANCA were associated with a higher prevalence of ear-nose-throat (ENT) (100% vs. 85.3%, p <0.0001), lung (100% vs. 89.7%, p = 0.0015), gastrointestinal involvement (60% vs. 17.6%, p <0.0001) and peripheral neuropathy (100% vs. 48.5%, p <0.0001). Kidney (0% vs. 16.2%, p <0.0001) and CNS involvement (0% vs. 13.2%, p = 0.0002) occurred less frequently in PTX3-ANCA positive patients. The 2 olfactomedin 4 (OLM4)-ANCA positive patients presented with ENT, lung and kidney involvement, and polyneuropathy, respectively.Table 1.ANCA in EGPA cohort (n = 73). BPI = bactericidal permeability-increasing protein.IFT / ELISANo. of patients (%)P-ANCA11 (15.1)C-ANCA5 (6.8)MPO-ANCA8 (10.9)PR3-ANCA2 (2.7)BPI-ANCA1 (1.4)PTX3-ANCA5 (6.8)OLM4-ANCA2 (2.7)ConclusionWe report on the detection of PTX3-, BPI- and OLM4-ANCA in addition to MPO- and PR3-ANCA in EGPA. OLM4-ANCA has been reported in 2 patients with non-vasculitic inflammatory symptoms previously [5]. Herein, detection of OLM4-ANCA in EGPA is reported for the first time. Our study shows that the presence of ANCA with various specificities other than MPO and PR3 contribute to a higher prevalence of ANCA in EGPA. Moreover, clinical manifestations differ between ANCA-negative EGPA and ANCA-positive EGPA, and between patients with different ANCA-specificities.