Lung immune signatures define two groups of end-stage IPF patients

BackgroundThe role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.MethodsTo investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters.ResultsWe identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities.ConclusionsIn end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored

Is auto-antibody expansion the turning point between idiopathic pulmonary fibrosis and rheumatoid arthritis?

We recently described that the presence of various anti-CarPs exhibited a consistent effect toward increasing the odds of ILD in RA. The anti-CarP-IgG isotype was most prevalent; however, anti-CarP-IgA had the highest OR (4.3),3 fueling the hypothesis that RA-related antibodies may originate in the respiratory mucosa, as suggested by Solomon et al. The high proportion of positive IgA-ACPA in IPF (21.3%-24.8%) in their study is noteworthy, in our opinion. This finding may be partially explained by the enzyme-linked immunosorbent assay test sensitivity considering that the proportion of positive IgA-ACPA in the healthy control subjects is also clearly higher (5.6%) than that observed in previous reports (< 2%).Peer reviewe

Lung immune signatures define two groups of end-stage IPF patients

Abstract Background The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial. Methods To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters. Results We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities. Conclusions In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored

Short and Long-Term Impact of COVID-19 Infection on Previous Respiratory Diseases.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities

Risk and outcome of COVID-19 infection in sarcoidosis patients:results of a self-reporting questionnaire

Background: It has been suggested that sarcoidosis patients, especially those on immunosuppressive medications, are at increased risk for COVID-19 infection and more severe disease. Methods: A questionnaire was developed in four languages (English, Dutch, Italian, and Spanish). The questionnaire queried whether patients had been infected with COVID-19 and outcome of the infection. Risk factors for COVID-19 infection were collected. Results: A total of 5200 sarcoidosis patients completed the questionnaire with 116 (2.23%) reporting infection and 18 (15.8%) required hospitalization. Increased hazard ratio (HR) for COVID-19 infection were seen for those with a COVID-19 infected roommate (HR=27.44, p</p