Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases

Abstract

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren’s syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto′s thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.

ANCA in patients with systemic lupus erythematosus. A cross sectional study in Brazilian patients and review of literature

“…Lactoferrin and cathepsin G are two additional antigens that have been shown to increase pANCA pattern. [34][35][36] Cathepsin G (CG) is an antimicrobial chymotrypsin-like enzyme that accounts for 18% of azurophil granule proteins. CG has been shown to act as a potent immune adjuvant by inducing the production of cytokines that promote T cell-dependent cellular immunity and antigen-specific Ig production.…”

Chemokine expression in sera of patients with microscopic polyangiitis and granulomatosis with polyangiitis

“…As disease severity is an important determinant of patient outcomes in AAV, studies have attempted to explore novel biomarkers, with a special focus on assessing disease activity 4 , 5 . Traditionally, laboratory tests of myeloperoxidase (MPO) and proteinase 3 (PR3)-ANCAs are useful biomarkers for the diagnosis and assessment of prognosis in the context of MPA/GPA 6 , but also with limitations that its titres alone are not sufficient to confirm diagnosis or monitor therapeutic response during follow‐up of patients 7 . In the meanwhile, the Birmingham Vasculitis Activity Score (BVAS) 3.0, which is composed of 56 items with a maximum score of 63, is a clinical measure for objectively describing ongoing inflammation in AAV 8 .…”