Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.

Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.

Centromere-associated protein A (CENP-A), a common autoimmune target in a subset of systemic sclerosis patients, appears to have no role to explain why its corresponding auto-antibodies are more frequently found in the limited than the diffuse form of systemic sclerosis. Therefore, we investigated t...

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Autores principales: Elvira Favoino, Liboria Digiglio, Giovanna Cuomo, Isabella E Favia, Vito Racanelli, Gabriele Valentini, Federico Perosa
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/424f70702e7941bb9a721aea2f430afd
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spelling oai:doaj.org-article:424f70702e7941bb9a721aea2f430afd2021-11-18T07:48:37ZAutoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.1932-620310.1371/journal.pone.0061453https://doaj.org/article/424f70702e7941bb9a721aea2f430afd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23613856/?tool=EBIhttps://doaj.org/toc/1932-6203Centromere-associated protein A (CENP-A), a common autoimmune target in a subset of systemic sclerosis patients, appears to have no role to explain why its corresponding auto-antibodies are more frequently found in the limited than the diffuse form of systemic sclerosis. Therefore, we investigated the fine specificity of anti-CENP-A antibodies as a first step to understanding their role in systemic sclerosis pathology. We focused on the amino-terminal portion of CENP-A spanning amino acids 1 to 17 (Ap(1-17)), which represents, along with Ap(17-30), an immunodominant epitope of the protein. Peptide Ap(1-17) was used to purify antibodies from 8 patients with systemic sclerosis. Anti-Ap(1-17) antibodies specifically reacted with human CENP-A but did not cross-react with CENP-B or Ap(17-30). Panning of a phage display peptide library with anti-Ap(1-17) antibodies from 2 patients identified two novel, partially overlapping motifs, <(5)Rx(st)xKP(10)> and <(9)KPxxPxR(15)> as the result of the alignment of specific phage clone insert sequences. Anti-Ap(1-17) IgG from the 8 patients had different reactivities to isolated phage clone insert sequences. Scanning the Swiss-Prot database revealed a large number of different types of proteins containing the two Ap(1-17) antigenic motifs. These data show that anti-CENP-A(1-17) antibodies are generated independently from anti-CENP-B antibodies and display great heterogeneity in their specificity by recognizing different motifs within that peptide sequence. This finding, along with the widespread interspecies and human tissue distribution of the two motifs, suggests that the number of motif-expressing proteins which can be the potential target of these antibodies is markedly higher than that estimated from the peptide-based epitope spreading model.Elvira FavoinoLiboria DigiglioGiovanna CuomoIsabella E FaviaVito RacanelliGabriele ValentiniFederico PerosaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61453 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elvira Favoino
Liboria Digiglio
Giovanna Cuomo
Isabella E Favia
Vito Racanelli
Gabriele Valentini
Federico Perosa
Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
description Centromere-associated protein A (CENP-A), a common autoimmune target in a subset of systemic sclerosis patients, appears to have no role to explain why its corresponding auto-antibodies are more frequently found in the limited than the diffuse form of systemic sclerosis. Therefore, we investigated the fine specificity of anti-CENP-A antibodies as a first step to understanding their role in systemic sclerosis pathology. We focused on the amino-terminal portion of CENP-A spanning amino acids 1 to 17 (Ap(1-17)), which represents, along with Ap(17-30), an immunodominant epitope of the protein. Peptide Ap(1-17) was used to purify antibodies from 8 patients with systemic sclerosis. Anti-Ap(1-17) antibodies specifically reacted with human CENP-A but did not cross-react with CENP-B or Ap(17-30). Panning of a phage display peptide library with anti-Ap(1-17) antibodies from 2 patients identified two novel, partially overlapping motifs, <(5)Rx(st)xKP(10)> and <(9)KPxxPxR(15)> as the result of the alignment of specific phage clone insert sequences. Anti-Ap(1-17) IgG from the 8 patients had different reactivities to isolated phage clone insert sequences. Scanning the Swiss-Prot database revealed a large number of different types of proteins containing the two Ap(1-17) antigenic motifs. These data show that anti-CENP-A(1-17) antibodies are generated independently from anti-CENP-B antibodies and display great heterogeneity in their specificity by recognizing different motifs within that peptide sequence. This finding, along with the widespread interspecies and human tissue distribution of the two motifs, suggests that the number of motif-expressing proteins which can be the potential target of these antibodies is markedly higher than that estimated from the peptide-based epitope spreading model.
format article
author Elvira Favoino
Liboria Digiglio
Giovanna Cuomo
Isabella E Favia
Vito Racanelli
Gabriele Valentini
Federico Perosa
author_facet Elvira Favoino
Liboria Digiglio
Giovanna Cuomo
Isabella E Favia
Vito Racanelli
Gabriele Valentini
Federico Perosa
author_sort Elvira Favoino
title Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
title_short Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
title_full Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
title_fullStr Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
title_full_unstemmed Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.
title_sort autoantibodies recognizing the amino terminal 1-17 segment of cenp-a display unique specificities in systemic sclerosis.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/424f70702e7941bb9a721aea2f430afd
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