Background: Anti-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].

Objectives: To investigate the spectrum of ANCA specificities in a multicenter cohort of patients with EGPA and identify novel ANCA antigens.

Methods: We 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.

Results: ANCA 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.

Conclusion: We 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.

REFERENCES:

[1]Schönermarck U, et al. Prevalence and spectrum of rheumatic diseases associated with proteinase 3-antineutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Rheumatology 2001;40:178-84.

[2]Bremer P, et al. Getting rid of MPO-ANCA: a matter of disease subtype. Rheumatology 2013:752-4.

[3]Comarmond C, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 2013;65:270-81.

[4]Padoan R, et al. IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis. J Autoimmun 2021;124:102725.

[5]Amirbeagi F, et al. Olfactomedin-4 autoantibodies give unusual c-ANCA staining patterns with reactivity to a subpopulation of neutrophils. J Leukoc Biol 2015;97:181-9.

Disclosure of Interests: None declared