Background Anti-endothelial cell antibodies (AECA) are frequently detected in anti-neutrophil cytoplasm antibodies (ANCA)-associated systemic vasculitis (AAV) and are considered to play pathological roles but their antigenic specificities are still unknown.
Objectives We used a proteomic approach combining two-dimensional electrophoresis and immunoblotting to identify the target antigens of AECA in patients with ANCA-associated vasculitis.
Methods Sera from 30 ANCA-associated vasculitis patients (12 with Granulomatosis with polyangeitis (GPA), 9 with microscopic polyangeitis (MPA), 9 with Churg Strauss syndrome (CSS)), tested in pools of 3 sera, were compared to a sera pool from 12 healthy controls (HC). Serum IgG reactivity was analyzed by use of a 2-D electrophoresis and immunoblotting technique with normal human umbilical vein endothelial cell (HUVEC) antigens.
Results Serum IgG in the HC sera pool recognized 85 protein spots and serum IgG from patients with AAV recognized 134±65 different protein spots. We focused on protein recognized by at least 3/4 pools of patients with GPA and 2/3 pools of patients with MPA and CSS and not by HC and identified 20, 7 and 8 proteins, respectively. In addition, among the 330 spots recognized by at least one pool of patients with AAV, ten different spots were recognized by at least 6/10 pools. Among identified proteins, IgG reactivity was detected against alpha-enolase, lamin A/C and protein disulfide-isomerase A3. Interestingly, Ingenuity Pathway Analysis revealed that most of these antigens interact with TGF-β and signalling pathways such as Jun and MAPK.
Conclusions AECA detected in patients with AAV recognize cellular targets playing key roles in cell biology. Target antigens interact with protein and complexes known to play a crucial role in AAV pathophysiology.
Disclosure of Interest: None Declared
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