Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes

Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial...

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Main Authors: Sonoko Harada, Motoyasu Kato, Kazuyuki Nakagome, Hitoshi Sasano, Yuki Tanabe, Tomohito Takeshige, Yuuki Sandhu, Kei Matsuno, Shoko Ueda, Sumiko Abe, Takayasu Nishimaki, Shun Shinomiya, Jun Ito, Sachiko Miyake, Ko Okumura, Makoto Nagata, Kazuhisa Takahashi, Norihiro Harada
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/122
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author Sonoko Harada
Motoyasu Kato
Kazuyuki Nakagome
Hitoshi Sasano
Yuki Tanabe
Tomohito Takeshige
Yuuki Sandhu
Kei Matsuno
Shoko Ueda
Sumiko Abe
Takayasu Nishimaki
Shun Shinomiya
Jun Ito
Sachiko Miyake
Ko Okumura
Makoto Nagata
Kazuhisa Takahashi
Norihiro Harada
author_facet Sonoko Harada
Motoyasu Kato
Kazuyuki Nakagome
Hitoshi Sasano
Yuki Tanabe
Tomohito Takeshige
Yuuki Sandhu
Kei Matsuno
Shoko Ueda
Sumiko Abe
Takayasu Nishimaki
Shun Shinomiya
Jun Ito
Sachiko Miyake
Ko Okumura
Makoto Nagata
Kazuhisa Takahashi
Norihiro Harada
author_sort Sonoko Harada
collection DOAJ
description Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4<sup>+</sup> T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD.
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spelling doaj-art-666d29063a4e41cc9d1fe8e143bce55b2025-01-24T13:25:16ZengMDPI AGBiomolecules2218-273X2025-01-0115112210.3390/biom15010122Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease SubtypesSonoko Harada0Motoyasu Kato1Kazuyuki Nakagome2Hitoshi Sasano3Yuki Tanabe4Tomohito Takeshige5Yuuki Sandhu6Kei Matsuno7Shoko Ueda8Sumiko Abe9Takayasu Nishimaki10Shun Shinomiya11Jun Ito12Sachiko Miyake13Ko Okumura14Makoto Nagata15Kazuhisa Takahashi16Norihiro Harada17Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama 350-0451, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama 350-0451, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Immunology, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanAtopy (Allergy) Research Center, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Saitama Medical University, Saitama 350-0451, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, JapanDiffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4<sup>+</sup> T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD.https://www.mdpi.com/2218-273X/15/1/122diffuse interstitial lung diseaseschronic eosinophilic pneumoniasarcoidosisidiopathic interstitial pneumoniachronic hypersensitivity pneumonitisconnective tissue disease-associated interstitial pneumonia
spellingShingle Sonoko Harada
Motoyasu Kato
Kazuyuki Nakagome
Hitoshi Sasano
Yuki Tanabe
Tomohito Takeshige
Yuuki Sandhu
Kei Matsuno
Shoko Ueda
Sumiko Abe
Takayasu Nishimaki
Shun Shinomiya
Jun Ito
Sachiko Miyake
Ko Okumura
Makoto Nagata
Kazuhisa Takahashi
Norihiro Harada
Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
Biomolecules
diffuse interstitial lung diseases
chronic eosinophilic pneumonia
sarcoidosis
idiopathic interstitial pneumonia
chronic hypersensitivity pneumonitis
connective tissue disease-associated interstitial pneumonia
title Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
title_full Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
title_fullStr Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
title_full_unstemmed Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
title_short Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes
title_sort evaluating the diagnostic value of lymphocyte subsets in bronchoalveolar lavage fluid and peripheral blood across various diffuse interstitial lung disease subtypes
topic diffuse interstitial lung diseases
chronic eosinophilic pneumonia
sarcoidosis
idiopathic interstitial pneumonia
chronic hypersensitivity pneumonitis
connective tissue disease-associated interstitial pneumonia
url https://www.mdpi.com/2218-273X/15/1/122
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