PMID- 33137121
OWN - NLM
STAT- MEDLINE
DCOM- 20201229
LR  - 20201229
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 11
DP  - 2020
TI  - CXCL9, CXCL10, and CXCL11; biomarkers of pulmonary inflammation associated with 
      autoimmunity in patients with collagen vascular diseases-associated interstitial 
      lung disease and interstitial pneumonia with autoimmune features.
PG  - e0241719
LID - 10.1371/journal.pone.0241719 [doi]
LID - e0241719
AB  - INTRODUCTION: Interstitial lung disease (ILD) is a heterogeneous group of 
      diseases characterized by varying degrees of lung inflammation and/or fibrosis. 
      We investigated biomarkers to infer whether patients with collagen vascular 
      diseases associated ILD (CVD-ILD) and interstitial pneumonia with autoimmune 
      features (IPAF) benefit from immunosuppressive therapy. MATERIALS AND METHODS: We 
      retrospectively investigated patients with CVD-ILD, IPAF, and idiopathic 
      pulmonary fibrosis (IPF) between June 2013 and May 2017 at our department. First, 
      we assessed differences in serum and bronchoalveolar lavage fluid (BALF) levels 
      of cytokines between groups. Second, we assessed the associations of patient's 
      clinical variables with serum and BALF levels of those cytokines that were 
      different between groups. Finally, we assessed the associations of diagnosis and 
      response to immunosuppressive therapy with serum levels of those cytokines that 
      were different between groups. RESULTS: We included 102 patients (51 with IPF, 35 
      with IPAF, and 16 with CVD-ILD). Serum and BALF levels of CXCL9, CXCL10, and 
      CXCL11 were significantly elevated in patients with IPAF or CVD-ILD compared with 
      those in patients with IPF. BALF levels of CXCL9 and CXCL10 were correlated with 
      the percentages of lymphocytes and macrophages in BALF. Serum levels of CXCL9 and 
      CXCL10 were correlated with BALF levels. Serum levels of CXCL9, CXCL10, and 
      CXCL11 were correlated C-reactive protein, percent predicted forced vital 
      capacity, alveolar-arterial oxygen difference, and the percentages of lymphocytes 
      and macrophages in BALF. Serum levels of CXCL9, CXCL10, and CXCL11 showed 
      moderate accuracy to distinguish patients with CVD-ILD from those with IPAF and 
      IPF. Pre-treatment serum levels of CXCL9 and CXCL11 showed strong positive 
      correlations with the annual forced vital capacity changes in patients with IPAF 
      and CVD-ILD treated with immunosuppressive drugs. CONCLUSIONS: Serum CXCL9, 
      CXCL10, and CXCL11 are potential biomarkers for autoimmune inflammation and 
      predictors of the immunosuppressive therapy responses in ILD with background 
      autoimmunity.
FAU - Kameda, Masami
AU  - Kameda M
AD  - Department of Respiratory Medicine and Allergology, Sapporo Medical University 
      School of Medicine, Sapporo, Hokkaido, Japan.
FAU - Otsuka, Mitsuo
AU  - Otsuka M
AD  - Department of Respiratory Medicine, Sapporo-Kosei General Hospital, Sapporo, 
      Hokkaido, Japan.
FAU - Chiba, Hirofumi
AU  - Chiba H
AD  - Department of Respiratory Medicine and Allergology, Sapporo Medical University 
      School of Medicine, Sapporo, Hokkaido, Japan.
FAU - Kuronuma, Koji
AU  - Kuronuma K
AUID- ORCID: 0000-0002-2743-3266
AD  - Department of Respiratory Medicine and Allergology, Sapporo Medical University 
      School of Medicine, Sapporo, Hokkaido, Japan.
FAU - Hasegawa, Takehiro
AU  - Hasegawa T
AUID- ORCID: 0000-0002-4635-4942
AD  - Sysmex Corporation, Kobe, Japan.
FAU - Takahashi, Hiroki
AU  - Takahashi H
AD  - Department of Rheumatology, Sapporo Medical University School of Medicine, 
      Sapporo, Hokkaido, Japan.
FAU - Takahashi, Hiroki
AU  - Takahashi H
AD  - Department of Respiratory Medicine and Allergology, Sapporo Medical University 
      School of Medicine, Sapporo, Hokkaido, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201102
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chemokine CXCL11)
RN  - 0 (Chemokine CXCL9)
RN  - 9007-34-5 (Collagen)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Aged
MH  - Autoimmunity
MH  - Biomarkers/analysis/*blood
MH  - Bronchoalveolar Lavage Fluid/chemistry/cytology/immunology
MH  - C-Reactive Protein/analysis
MH  - Chemokine CXCL10/analysis/*blood
MH  - Chemokine CXCL11/analysis/*blood
MH  - Chemokine CXCL9/analysis/*blood
MH  - Collagen/metabolism
MH  - Female
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/diagnosis
MH  - Lung Diseases, Interstitial/*diagnosis/etiology
MH  - Lymphocytes/cytology/metabolism
MH  - Macrophages/cytology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Vascular Diseases/*complications/pathology
MH  - Vital Capacity
PMC - PMC7605704
COIS- Masami Kameda, Mitsuo Otsuka, and Takehiro Hasegawa have a pending patent 
      application belonging to Sysmex Corporation and Sapporo Medical University. This 
      does not alter our adherence to PLOS ONE policies on materials.
EDAT- 2020/11/03 06:00
MHDA- 2020/12/30 06:00
PMCR- 2020/11/02
CRDT- 2020/11/02 17:13
PHST- 2020/07/23 00:00 [received]
PHST- 2020/10/20 00:00 [accepted]
PHST- 2020/11/02 17:13 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2020/12/30 06:00 [medline]
PHST- 2020/11/02 00:00 [pmc-release]
AID - PONE-D-20-22949 [pii]
AID - 10.1371/journal.pone.0241719 [doi]
PST - epublish
SO  - PLoS One. 2020 Nov 2;15(11):e0241719. doi: 10.1371/journal.pone.0241719. 
      eCollection 2020.