B cell‐activating factors in autoimmune pulmonary alveolar proteinosis
Abstract 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 invo...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-03-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-01755-y |
| _version_ | 1819163876387717120 |
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| author | Masaki Hirose Toru Arai Chikatoshi Sugimoto Takayuki Takimoto Reiko Sugawara Shojiro Minomo Sayoko Shintani Naoko Takeuchi Kanako Katayama Yasushi Inoue Tomoko Kagawa Takahiko Kasai Masanori Akira Yoshikazu Inoue |
| author_facet | Masaki Hirose Toru Arai Chikatoshi Sugimoto Takayuki Takimoto Reiko Sugawara Shojiro Minomo Sayoko Shintani Naoko Takeuchi Kanako Katayama Yasushi Inoue Tomoko Kagawa Takahiko Kasai Masanori Akira Yoshikazu Inoue |
| author_sort | Masaki Hirose |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T17:51:06Z |
| format | Article |
| id | doaj.art-bb8074ba53104c0d8efa7e0a63cef45d |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T17:51:06Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-bb8074ba53104c0d8efa7e0a63cef45d2022-12-21T18:18:11ZengBMCOrphanet Journal of Rare Diseases1750-11722021-03-0116111010.1186/s13023-021-01755-yB cell‐activating factors in autoimmune pulmonary alveolar proteinosisMasaki Hirose0Toru Arai1Chikatoshi Sugimoto2Takayuki Takimoto3Reiko Sugawara4Shojiro Minomo5Sayoko Shintani6Naoko Takeuchi7Kanako Katayama8Yasushi Inoue9Tomoko Kagawa10Takahiko Kasai11Masanori Akira12Yoshikazu Inoue13Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical CenterClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Pathology, National Hospital Organization Kinki-Chuo Chest Medical CenterDepartment of Radiology, National Hospital Organization Kinki-Chuo Chest Medical CenterClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical CenterAbstract 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.https://doi.org/10.1186/s13023-021-01755-yAutoimmune pulmonary alveolar proteinosisB cell‐activating factorBiomarker |
| spellingShingle | Masaki Hirose Toru Arai Chikatoshi Sugimoto Takayuki Takimoto Reiko Sugawara Shojiro Minomo Sayoko Shintani Naoko Takeuchi Kanako Katayama Yasushi Inoue Tomoko Kagawa Takahiko Kasai Masanori Akira Yoshikazu Inoue B cell‐activating factors in autoimmune pulmonary alveolar proteinosis Orphanet Journal of Rare Diseases Autoimmune pulmonary alveolar proteinosis B cell‐activating factor Biomarker |
| 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 | Autoimmune pulmonary alveolar proteinosis B cell‐activating factor Biomarker |
| url | https://doi.org/10.1186/s13023-021-01755-y |
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