Dataset Information

Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

ABSTRACT: The types of cells most significantly linked to individual subtypes of idiopathic interstitial pneumonias (IIPs) remain unclear. Few studies have examined CD163+ macrophages in IIPs.We retrospectively aimed to immunohistochemically characterize the CD163+ macrophages in IIPs.Paraffin-embedded lung tissue samples were obtained from 47 patients with IIPs, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (NSIP), and cryptogenic organizing pneumonia (COP), and 12 normal controls were immunohistochemically analyzed, using primary antibodies against CD68 and CD163 as indicators of pan and M2 macrophages, respectively.CD68+ macrophage density was significantly increased in the 3 subtypes of IIPs relative to that in the control group, although no difference was detected within the different IIPs. CD163+ macrophage density was significantly increased in NSIP and COP samples relative to that in IPF samples. The density ratio of CD163+ macrophages to CD68+ macrophages was significantly decreased in IPF/UIP samples relative to that in the others, while the densities in NSIP and COP were significantly higher than those in control cases.CD163+ macrophages show distinct profiles among IIPs, and the standardized numerical density is decreased in IPF cases that have poor prognoses.

SUBMITTER: Yamashita M

PROVIDER: S-EPMC5817286 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

Yamashita Masahiro M Saito Ryoko R Yasuhira Shinji S Fukuda Yuh Y Sasamo Hironobu H Sugai Tamotsu T Yamauchi Kohei K Maemondo Makoto M

Journal of immunology research 20180204

<h4>Background</h4>The types of cells most significantly linked to individual subtypes of idiopathic interstitial pneumonias (IIPs) remain unclear. Few studies have examined CD163<sup>+</sup> macrophages in IIPs.<h4>Objective</h4>We retrospectively aimed to immunohistochemically characterize the CD163<sup>+</sup> macrophages in IIPs.<h4>Methods</h4>Paraffin-embedded lung tissue samples were obtained from 47 patients with IIPs, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific ...[more]

PMID: 29507864

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Project description:BackgroundPleuroparenchymal fibroelastosis (PPFE) is characterised by predominant upper lobe pleural and subpleural lung parenchymal fibrosis. Radiological PPFE-like lesion has been associated with various types of interstitial lung diseases. However, the prevalence and clinical significance of radiological PPFE-like lesion in patients with idiopathic interstitial pneumonias (IIPs) are not fully understood. We aimed to determine the prevalence and clinical impact on survival of radiological PPFE-like lesion in patients with IIPs.MethodsA post-hoc analysis was conducted using data from the Japanese nationwide cloud-based database of patients with IIPs. All the patients in the database were diagnosed as having IIPs by multidisciplinary discussion. Patients diagnosed with idiopathic PPFE were excluded. Clinical data and chest computed tomography (CT) image of 419 patients with IIPs were analysed. The presence of radiological PPFE-like lesion was independently evaluated by two chest radiologists blind to the clinical data.ResultsOf the 419 patients with IIPs, radiological PPFE-like lesions were detected in 101 (24.1%) patients, mainly in idiopathic pulmonary fibrosis (IPF) and unclassifiable IIPs, but less in idiopathic nonspecific interstitial pneumonia. Prognostic analyses revealed that radiological PPFE-like lesion was significantly associated with poor outcome in patients with IIPs, which was independent of age, IPF diagnosis and %FVC. In survival analyses, the patients with radiological PPFE-like lesions had poor survival compared with those without (log-rank, p < 0.0001). Subgroup analyses demonstrated that radiological PPFE-like lesion was significantly associated with poor survival both in patients with IPF and those with unclassifiable IIPs.ConclusionRadiological PPFE-like lesion is a condition that could exist in IIPs, mainly in IPF and unclassifiable IIPs. Importantly, the radiological PPFE-like lesion is a non-invasive marker to predict poor outcome in patients with IIPs, which should be carefully considered in clinical practice.

Project description:BACKGROUND:Idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous, somewhat unpredictable diseases characterized by progressive scarring of the interstitium. Since lung function is a key determinant of survival, we reasoned that the transcriptional profile in IIP lung tissue would be associated with measures of lung function, and could enhance prognostic approaches to IIPs. RESULTS:Using gene expression profiling of 167 lung tissue specimens with IIP diagnosis and 50 control lungs, we identified genes whose expression is associated with changes in lung function (% predicted FVC and % predicted DLCO) modeled as categorical (severe vs mild disease) or continuous variables while adjusting for smoking status and IIP subtype; false discovery rate (FDR) approach was used to correct for multiple comparisons. This analysis identified 58 transcripts that are associated with mild vs severe disease (categorical analysis), including those with established role in fibrosis (ADAMTS4, ADAMTS9, AGER, HIF-1?, SERPINA3, SERPINE2, and SELE) as well as novel IIP candidate genes such as rhotekin 2 (RTKN2) and peptidase inhibitor 15 (PI15). Protein-protein interactome analysis of 553 genes whose expression is significantly associated with lung function when modeled as continuous variables demonstrates that more severe presentation of IIPs is characterized by an increase in cell cycle progression and apoptosis, increased hypoxia, and dampened innate immune response. Our findings were validated in an independent cohort of 131 IIPs and 40 controls at the mRNA level and for one gene (RTKN2) at the protein level by immunohistochemistry in a subset of samples. CONCLUSIONS:We identified commonalities and differences in gene expression among different subtypes of IIPs. Disease progression, as characterized by lower measures of FVC and DLCO, results in marked changes in expression of novel and established genes and pathways involved in IIPs. These genes and pathways represent strong candidates for biomarker studies and potential therapeutic targets for IIP severity.

Dataset Information

Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

Publications

Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

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