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B cell‐activating factors in autoimmune pulmonary alveolar proteinosis
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923513/ https://www.ncbi.nlm.nih.gov/pubmed/33653382 http://dx.doi.org/10.1186/s13023-021-01755-y |
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author | Hirose, Masaki Arai, Toru Sugimoto, Chikatoshi Takimoto, Takayuki Sugawara, Reiko Minomo, Shojiro Shintani, Sayoko Takeuchi, Naoko Katayama, Kanako Inoue, Yasushi Kagawa, Tomoko Kasai, Takahiko Akira, Masanori Inoue, Yoshikazu |
author_facet | Hirose, Masaki Arai, Toru Sugimoto, Chikatoshi Takimoto, Takayuki Sugawara, Reiko Minomo, Shojiro Shintani, Sayoko Takeuchi, Naoko Katayama, Kanako Inoue, Yasushi Kagawa, Tomoko Kasai, Takahiko Akira, Masanori Inoue, Yoshikazu |
author_sort | Hirose, Masaki |
collection | PubMed |
description | BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. SUBJECTS AND METHODS: BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. RESULTS: In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF. CONCLUSIONS: BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP. |
format | Online Article Text |
id | pubmed-7923513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79235132021-03-02 B cell‐activating factors in autoimmune pulmonary alveolar proteinosis Hirose, Masaki Arai, Toru Sugimoto, Chikatoshi Takimoto, Takayuki Sugawara, Reiko Minomo, Shojiro Shintani, Sayoko Takeuchi, Naoko Katayama, Kanako Inoue, Yasushi Kagawa, Tomoko Kasai, Takahiko Akira, Masanori Inoue, Yoshikazu Orphanet J Rare Dis Research BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. SUBJECTS AND METHODS: BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. RESULTS: In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p < 0.0001 and p < 0.05, respectively), and BALF BAFF and APRIL levels were significantly increased versus disease controls (p < 0.0001 and p < 0.01, respectively). Serum BAFF levels (but not APRIL levels) were significantly correlated with Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, SP-A, and lactate dehydrogenase (p < 0.0001). There was no significant correlation between serum BAFF or APRIL levels and anti-GM-CSF autoantibody. BAFF and APRIL were negatively correlated with single-breath diffusion capacity for carbon monoxide (DLco) (p = 0.004) and forced vital capacity (p = 0.04), respectively. BAFF (but not APRIL) in BALF was negatively correlated with vital capacity (p = 0.04) and DLco (p = 0.006). There were significant correlations between disease severity and BAFF levels in serum (p = 0.04) and BALF (p = 0.007). Serum levels of anti-GM-CSF autoantibody, BAFF, and APRIL were not significantly affected by WLL or inhalation of recombinant human GM-CSF. CONCLUSIONS: BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP. BioMed Central 2021-03-02 /pmc/articles/PMC7923513/ /pubmed/33653382 http://dx.doi.org/10.1186/s13023-021-01755-y Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hirose, Masaki Arai, Toru Sugimoto, Chikatoshi Takimoto, Takayuki Sugawara, Reiko Minomo, Shojiro Shintani, Sayoko Takeuchi, Naoko Katayama, Kanako Inoue, Yasushi Kagawa, Tomoko Kasai, Takahiko Akira, Masanori Inoue, Yoshikazu B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title | B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title_full | B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title_fullStr | B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title_full_unstemmed | B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title_short | B cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
title_sort | b cell‐activating factors in autoimmune pulmonary alveolar proteinosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923513/ https://www.ncbi.nlm.nih.gov/pubmed/33653382 http://dx.doi.org/10.1186/s13023-021-01755-y |
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