Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis Article Swipe
Aleeza J. Roth
,
Joshua D. Ooi
,
Jacob J. Hess
,
Mirjan M. van Timmeren
,
Elisabeth A. Berg
,
Caroline J. Poulton
,
JulieAnne McGregor
,
Madelyn Burkart
,
Susan L. Hogan
,
Yichun Hu
,
Witold Winnik
,
Patrick H. Nachman
,
Coen A. Stegeman
,
John D. Niles
,
Peter Heeringa
,
A. Richard Kitching
,
Stephen R. Holdsworth
,
J. Charles Jennette
,
Gloria A. Preston
,
Ronald J. Falk
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/yv1b-6n44
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/yv1b-6n44
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.
Related Topics
Concepts
Pathogenicity
Epitope
ANCA-Associated Vasculitis
Vasculitis
Biology
Immunology
Computational biology
Medicine
Microbiology
Antibody
Pathology
Disease
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.17615/yv1b-6n44
- OA Status
- green
- Related Works
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4297970023Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.17615/yv1b-6n44Digital Object Identifier
- Title
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Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
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2020Year of publication
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2020-11-04Full publication date if available
- Authors
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Aleeza J. Roth, Joshua D. Ooi, Jacob J. Hess, Mirjan M. van Timmeren, Elisabeth A. Berg, Caroline J. Poulton, JulieAnne McGregor, Madelyn Burkart, Susan L. Hogan, Yichun Hu, Witold Winnik, Patrick H. Nachman, Coen A. Stegeman, John D. Niles, Peter Heeringa, A. Richard Kitching, Stephen R. Holdsworth, J. Charles Jennette, Gloria A. Preston, Ronald J. FalkList of authors in order
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https://doi.org/10.17615/yv1b-6n44Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.17615/yv1b-6n44Direct OA link when available
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Pathogenicity, Epitope, ANCA-Associated Vasculitis, Vasculitis, Biology, Immunology, Computational biology, Medicine, Microbiology, Antibody, Pathology, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.from | 77, 98, 105 |
| abstract_inverted_index.sole | 127 |
| abstract_inverted_index.some | 21, 45 |
| abstract_inverted_index.that | 95, 123, 192 |
| abstract_inverted_index.this | 112, 132 |
| abstract_inverted_index.wall | 16 |
| abstract_inverted_index.were | 82 |
| abstract_inverted_index.why, | 43 |
| abstract_inverted_index.with | 53, 73 |
| abstract_inverted_index.These | 179 |
| abstract_inverted_index.cases | 22 |
| abstract_inverted_index.exist | 62 |
| abstract_inverted_index.human | 78 |
| abstract_inverted_index.mice. | 152 |
| abstract_inverted_index.other | 199 |
| abstract_inverted_index.small | 4 |
| abstract_inverted_index.study | 32 |
| abstract_inverted_index.their | 140 |
| abstract_inverted_index.these | 159 |
| abstract_inverted_index.those | 106 |
| abstract_inverted_index.using | 85 |
| abstract_inverted_index.vitro | 146 |
| abstract_inverted_index.which | 171 |
| abstract_inverted_index.assays | 49 |
| abstract_inverted_index.cases, | 46 |
| abstract_inverted_index.caused | 9 |
| abstract_inverted_index.common | 197 |
| abstract_inverted_index.highly | 87 |
| abstract_inverted_index.induce | 149 |
| abstract_inverted_index.linear | 128 |
| abstract_inverted_index.mapped | 84 |
| abstract_inverted_index.murine | 80 |
| abstract_inverted_index.serum, | 170 |
| abstract_inverted_index.sought | 33 |
| abstract_inverted_index.vessel | 5, 15 |
| abstract_inverted_index.against | 125, 131 |
| abstract_inverted_index.disease | 54, 122 |
| abstract_inverted_index.epitope | 40, 83, 89, 102, 133 |
| abstract_inverted_index.explain | 42 |
| abstract_inverted_index.healthy | 99 |
| abstract_inverted_index.present | 107 |
| abstract_inverted_index.reacted | 124 |
| abstract_inverted_index.samples | 81 |
| abstract_inverted_index.suggest | 191 |
| abstract_inverted_index.whether | 36 |
| abstract_inverted_index.MPO-ANCA | 119 |
| abstract_inverted_index.activate | 143 |
| abstract_inverted_index.allowing | 177 |
| abstract_inverted_index.anti-MPO | 59 |
| abstract_inverted_index.capacity | 141 |
| abstract_inverted_index.disease. | 75, 110 |
| abstract_inverted_index.epitopes | 183 |
| abstract_inverted_index.findings | 180 |
| abstract_inverted_index.fragment | 166 |
| abstract_inverted_index.patients | 72 |
| abstract_inverted_index.presence | 25, 163 |
| abstract_inverted_index.purified | 175 |
| abstract_inverted_index.activity, | 55 |
| abstract_inverted_index.approach. | 92 |
| abstract_inverted_index.correlate | 52 |
| abstract_inverted_index.detection | 157 |
| abstract_inverted_index.determine | 35 |
| abstract_inverted_index.diagnosed | 19 |
| abstract_inverted_index.different | 104 |
| abstract_inverted_index.discovery | 117 |
| abstract_inverted_index.diseases. | 201 |
| abstract_inverted_index.diversity | 194 |
| abstract_inverted_index.implicate | 181 |
| abstract_inverted_index.indicated | 94 |
| abstract_inverted_index.naturally | 57 |
| abstract_inverted_index.nephritis | 150 |
| abstract_inverted_index.occurring | 58 |
| abstract_inverted_index.pathology | 186 |
| abstract_inverted_index.sensitive | 88 |
| abstract_inverted_index.sequence. | 129 |
| abstract_inverted_index.serologic | 48 |
| abstract_inverted_index.antibodies | 28 |
| abstract_inverted_index.autoimmune | 200 |
| abstract_inverted_index.confounder | 154 |
| abstract_inverted_index.detection. | 178 |
| abstract_inverted_index.eliminated | 173 |
| abstract_inverted_index.pathogenic | 135 |
| abstract_inverted_index.undetected | 70 |
| abstract_inverted_index.vasculitis | 7, 189 |
| abstract_inverted_index.(MPO-ANCA). | 29 |
| abstract_inverted_index.cytoplasmic | 1 |
| abstract_inverted_index.differences | 37 |
| abstract_inverted_index.individuals | 100 |
| abstract_inverted_index.methodology | 113 |
| abstract_inverted_index.multicenter | 31 |
| abstract_inverted_index.necrotizing | 6 |
| abstract_inverted_index.neutrophils | 144 |
| abstract_inverted_index.properties, | 136 |
| abstract_inverted_index.serological | 156 |
| abstract_inverted_index.specificity | 41 |
| abstract_inverted_index.Importantly, | 111 |
| abstract_inverted_index.autoantibody | 193 |
| abstract_inverted_index.conventional | 47 |
| abstract_inverted_index.demonstrated | 138 |
| abstract_inverted_index.disease-free | 64 |
| abstract_inverted_index.individuals, | 65 |
| abstract_inverted_index.inflammation | 12 |
| abstract_inverted_index.spectrometry | 91 |
| abstract_inverted_index.ANCA-negative | 74, 121 |
| abstract_inverted_index.ceruloplasmin | 168 |
| abstract_inverted_index.excision/mass | 90 |
| abstract_inverted_index.specificities | 103 |
| abstract_inverted_index.Autoantibodies | 76, 130 |
| abstract_inverted_index.autoantibodies | 60, 97, 160 |
| abstract_inverted_index.immunodominant | 182 |
| abstract_inverted_index.ANCA-associated | 188 |
| abstract_inverted_index.Anti-neutrophil | 0 |
| abstract_inverted_index.immune-mediated | 11 |
| abstract_inverted_index.(ANCA-associated) | 3 |
| abstract_inverted_index.antibody–associated | 2 |
| abstract_inverted_index.myeloperoxidase-specific | 27 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 20 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/2 |
| sustainable_development_goals[0].score | 0.44999998807907104 |
| sustainable_development_goals[0].display_name | Zero hunger |
| citation_normalized_percentile.value | 0.38226457 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |