scholarly journals Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis

2020 ◽  
Vol 8 (9) ◽  
Author(s):  
Lv Liu ◽  
Jieli Qin ◽  
Ting Guo ◽  
Ping Chen ◽  
Ruoyun Ouyang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Functional Characterization ◽  
Surfactant Protein ◽  
Chinese Family

Increased Surfactant Protein-A Levels in Patients With Newly Diagnosed Idiopathic Pulmonary Fibrosis

CHEST Journal ◽  
2004 ◽  
Vol 125 (2) ◽  
pp. 617-625 ◽  
Author(s):  
David S. Phelps ◽  
Todd M. Umstead ◽  
Mayra Mejia ◽  
Guillermo Carrillo ◽  
Annie Pardo ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Newly Diagnosed

scholarly journals Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kimiyuki Ikeda ◽  
◽  
Hirofumi Chiba ◽  
Hirotaka Nishikiori ◽  
Arata Azuma ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Placebo Group ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Treatment Period ◽  
Surfactant Protein ◽  
Phase 3 ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. Methods We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. Results In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. Conclusions Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp)

scholarly journals Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Kosuke Hamai ◽  
Hiroshi Iwamoto ◽  
Nobuhisa Ishikawa ◽  
Yasushi Horimasu ◽  
Takeshi Masuda ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Bacterial Pneumonia ◽  
Protein A ◽  
Survival Rates ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Survival Prediction ◽  
Healthy Controls ◽  
Disease Markers

Background.Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D.Methods.The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF.Results.The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic.Conclusions.The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF.

scholarly journals Role of Immune Checkpoint Proteins in Idiopathic Pulmonary Fibrosis

2017 ◽  
Author(s):  
David M Habiel ◽  
Milena Espindola ◽  
Chris Kitson ◽  
Anthony Azzara ◽  
Ana Lucia Coelho ◽  
...  
Keyword(s):  
T Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Checkpoint ◽  
Flow Cytometric Analysis ◽  
Lymphocyte Activation ◽  
Surfactant Protein ◽  
Nsg Mice ◽  
Immune Checkpoint Proteins

AbstractIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Due to the lack of clinical efficacy of standard immuno-suppressants in IPF, the role of the immune response in this disease remains elusive. Nevertheless, previous reports have shown that increased T cell numbers and phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Transcriptomic analysis of CD3+ T cells isolated from IPF lungs removed prior to lung transplant (i.e. explant lung) revealed a loss of CD28 expression and both elevated checkpoint and lymphocyte activation pathways. Flow cytometric analysis of a mixture of immune and non-immune cells isolated from explanted IPF lungs showed elevated PD-1 and CTLA4 protein expression on CD4- lymphocytes and PD-L1 expression on EpCAM+ and CD45- EpCAM- cells. Lung remodeling and loss of BAL surfactant protein C were observed in NOD SCID IL-2Rγ-/- (NSG) mice that received an intravenous injection of a mixture of IPF cells, including purified IPF T cells. Finally, in humanized NSG mice, anti-CTLA4, but not anti-PD1, mAb treatment induced an expansion of CD3+ T cells and accelerated lung fibrosis. Together, these results demonstrate that IPF T cells are profibrotic but the immune checkpoint protein, CTLA-4, appears to limit this effect in IPF.

scholarly journals Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways

2021 ◽  
Author(s):  
Enxhi Shaba ◽  
Claudia Landi ◽  
Alfonso Carleo ◽  
Lorenza Vantaggiato ◽  
Eugenio Paccagnini ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lavage Fluid ◽  
Isolation Technique ◽  
Complex Samples ◽  
Protein Functions ◽  
Proteomic Investigation ◽  
Scatter Plots ◽  
Cytoskeleton Remodeling

In the longtime challenge of identifying specific, easily-detectable and reliable biomarkers of Idiopathic Pulmonary Fibrosis (IPF), bronchoalveolar lavage fluid (BALF) proteomics is providing interesting new insights into its pathogenesis. To the best of our knowledge, the present study is the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was chosen as EVs isolation technique and their purification was assessed by TEM, 2DE and LC-MS/MS. Our 2DE data and scatter plots showed considerable differences between the proteome of EVs and that of whole BALF and of its fluid component. Analysis of protein content and protein functions evidenced that EV proteins are predominantly involved in cytoskeleton remodeling, adenosine signaling, adrenergic signaling, C-peptide signaling and lipid metabolism. Our findings may suggest a wider system involvement in the disease pathogenesis and support the importance of pre-fractioning of complex samples, like BALF, in order to let low-abundant proteins-mediated pathways to emerge.

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