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Citations to this article

Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis
Aleeza J. Roth, … , Gloria A. Preston, Ronald J. Falk
Aleeza J. Roth, … , Gloria A. Preston, Ronald J. Falk
Published March 15, 2013
Citation Information: J Clin Invest. 2013;123(4):1773-1783. https://doi.org/10.1172/JCI65292.
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Research Article Immunology Article has an altmetric score of 21

Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis

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Abstract

Anti-neutrophil cytoplasmic antibody–associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). This multicenter study sought to determine whether differences in ANCA epitope specificity explain why, in some cases, conventional serologic assays do not correlate with disease activity, why naturally occurring anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are undetected in patients with ANCA-negative disease. Autoantibodies from human and murine samples were epitope mapped using a highly sensitive epitope excision/mass spectrometry approach. Data indicated that MPO autoantibodies from healthy individuals had epitope specificities different from those present in ANCA disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA-negative disease that reacted against a sole linear sequence. Autoantibodies against this epitope had pathogenic properties, as demonstrated by their capacity to activate neutrophils in vitro and to induce nephritis in mice. The confounder for serological detection of these autoantibodies was the presence of a fragment of ceruloplasmin in serum, which was eliminated in purified IgG, allowing detection. These findings implicate immunodominant epitopes in the pathology of ANCA-associated vasculitis and suggest that autoantibody diversity may be common to other autoimmune diseases.

Authors

Aleeza J. Roth, Joshua D. Ooi, Jacob J. Hess, Mirjan M. van Timmeren, Elisabeth A. Berg, Caroline E. Poulton, JulieAnne McGregor, Madelyn Burkart, Susan L. Hogan, Yichun Hu, Witold Winnik, Patrick H. Nachman, Coen A. Stegeman, John Niles, Peter Heeringa, A. Richard Kitching, Stephen Holdsworth, J. Charles Jennette, Gloria A. Preston, Ronald J. Falk

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 Total
Citations: 6 7 4 5 12 10 7 14 7 15 9 9 3 108
Citation information
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Citations to this article in year 2017 (7)

Title and authors Publication Year
Mechanisms of Autoantibody-Induced Pathology
RJ Ludwig, K Vanhoorelbeke, F Leypoldt, Z Kaya, K Bieber, SM McLachlan, L Komorowski, J Luo, O Cabral-Marques, CM Hammers, JM Lindstrom, P Lamprecht, A Fischer, G Riemekasten, C Tersteeg, P Sondermann, B Rapoport, KP Wandinger, C Probst, AE Beidaq, E Schmidt, A Verkman, RA Manz, F Nimmerjahn
Frontiers in immunology 2017
Pulmonary Involvement in Systemic Vasculitis
LF Flores-Suárez, MA Alba, H Mateos-Toledo, N Ruiz
Current Rheumatology Reports 2017
ANCA Glomerulonephritis and Vasculitis
JC Jennette, PH Nachman
Clinical journal of the American Society of Nephrology : CJASN 2017
Clinical value of systemic symptoms in IgA nephropathy with ANCA positivity
L Xie, J He, X Liu, S Tang, W Wang, F Li, Y Zhang, J Zhang, Y Huang, J Zhao, Y Li, J Zhang
Clinical Rheumatology 2017
Anti-glomerular basement membrane disease: Case series from a tertiary center in North India
D Prabhakar, M Rathi, R Nada, RW Minz, V Kumar, HS Kohli, V Jha, KL Gupta
Indian journal of nephrology 2017
Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis
SW Olson, JJ Lee, M Poirier, DJ Little, LK Prince, TP Baker, JD Edison, KC Abbott
Autoimmune Diseases 2017
Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis developed from ANCA negative renal limited vasculitis: A case report.
Li XL, Xu PC, Chen T, Yan TK, Jiang JQ, Jia JY, Wei L, Shang WY, Hu SY
Medicine 2017

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ISSN: 0021-9738 (print), 1558-8238 (online)

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