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Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension

While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodi...

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Autores principales: Naito, Akira, Hiwasa, Takaki, Tanabe, Nobuhiro, Sanada, Takayuki Jujo, Sugiura, Toshihiko, Shigeta, Ayako, Terada, Jiro, Takizawa, Hirotaka, Kashiwado, Koichi, Sakao, Seiichiro, Tatsumi, Koichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373903/
https://www.ncbi.nlm.nih.gov/pubmed/30759165
http://dx.doi.org/10.1371/journal.pone.0211377
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author Naito, Akira
Hiwasa, Takaki
Tanabe, Nobuhiro
Sanada, Takayuki Jujo
Sugiura, Toshihiko
Shigeta, Ayako
Terada, Jiro
Takizawa, Hirotaka
Kashiwado, Koichi
Sakao, Seiichiro
Tatsumi, Koichiro
author_facet Naito, Akira
Hiwasa, Takaki
Tanabe, Nobuhiro
Sanada, Takayuki Jujo
Sugiura, Toshihiko
Shigeta, Ayako
Terada, Jiro
Takizawa, Hirotaka
Kashiwado, Koichi
Sakao, Seiichiro
Tatsumi, Koichiro
author_sort Naito, Akira
collection PubMed
description While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodies in CTEPH patients. Initial screening was performed in 5 CTEPH patients and 5 healthy donors (HDs) using a ProtoArray Human Protein Microarray v5.1 containing 9,375 human proteins, and we selected 34 antigens recognized by IgG antibodies more strongly in the sera of CTEPH patients than in the sera of HDs. In subsequent second/third analyses, we validated the auto-antibody level using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 96 CTEPH patients and 96 HDs as follows: At the second screening, we used 63 crude peptides derived from those selected 34 antigens and found that the serum levels of autoantibodies for 4 peptides seemed higher in CTEPH patients than in HDs. In third analysis, we used the purified peptides of those selected in second screening and found that serum antibodies against peptides derived from exonuclease 3'-5' domain-containing 2 (EXD2) and phosphorylated adaptor for RNA export (PHAX) were significantly higher in CTEPH patients than in HDs. The serum antibody levels to these antigens were also elevated in PAH patients. The titers against EXD2 peptide decreased after surgical treatment in CTEPH patients. These autoantibodies may be useful as biomarkers of CTEPH and PAH, and further investigations may provide novel insight into the etiology.
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spelling pubmed-63739032019-03-01 Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension Naito, Akira Hiwasa, Takaki Tanabe, Nobuhiro Sanada, Takayuki Jujo Sugiura, Toshihiko Shigeta, Ayako Terada, Jiro Takizawa, Hirotaka Kashiwado, Koichi Sakao, Seiichiro Tatsumi, Koichiro PLoS One Research Article While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodies in CTEPH patients. Initial screening was performed in 5 CTEPH patients and 5 healthy donors (HDs) using a ProtoArray Human Protein Microarray v5.1 containing 9,375 human proteins, and we selected 34 antigens recognized by IgG antibodies more strongly in the sera of CTEPH patients than in the sera of HDs. In subsequent second/third analyses, we validated the auto-antibody level using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 96 CTEPH patients and 96 HDs as follows: At the second screening, we used 63 crude peptides derived from those selected 34 antigens and found that the serum levels of autoantibodies for 4 peptides seemed higher in CTEPH patients than in HDs. In third analysis, we used the purified peptides of those selected in second screening and found that serum antibodies against peptides derived from exonuclease 3'-5' domain-containing 2 (EXD2) and phosphorylated adaptor for RNA export (PHAX) were significantly higher in CTEPH patients than in HDs. The serum antibody levels to these antigens were also elevated in PAH patients. The titers against EXD2 peptide decreased after surgical treatment in CTEPH patients. These autoantibodies may be useful as biomarkers of CTEPH and PAH, and further investigations may provide novel insight into the etiology. Public Library of Science 2019-02-13 /pmc/articles/PMC6373903/ /pubmed/30759165 http://dx.doi.org/10.1371/journal.pone.0211377 Text en © 2019 Naito et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Naito, Akira
Hiwasa, Takaki
Tanabe, Nobuhiro
Sanada, Takayuki Jujo
Sugiura, Toshihiko
Shigeta, Ayako
Terada, Jiro
Takizawa, Hirotaka
Kashiwado, Koichi
Sakao, Seiichiro
Tatsumi, Koichiro
Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title_full Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title_fullStr Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title_full_unstemmed Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title_short Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension
title_sort elevated levels of autoantibodies against exd2 and phax in the sera of patients with chronic thromboembolic pulmonary hypertension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373903/
https://www.ncbi.nlm.nih.gov/pubmed/30759165
http://dx.doi.org/10.1371/journal.pone.0211377
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