scholarly journals Two distinct immunopathological profiles in lungs of lethal COVID-19

2020 ◽  
Author(s):  
Ronny Nienhold ◽  
Yari Ciani ◽  
Viktor Koelzer ◽  
Alexandar Tzankov ◽  
Jasmin Haslbauer ◽  
...  
Keyword(s):  
Immune Responses ◽  
The Other ◽  
High Expression ◽  
Normal Lung ◽  
Post Mortem ◽  
Viral Loads ◽  
Interferon Stimulated Genes ◽  
Hospitalization Time ◽  
Pulmonary Damage ◽  
Reaction Patterns

Abstract Immune responses in lungs of Coronavirus Disease 2019 (COVID-19) are poorly characterized. We conducted transcriptomic, histologic and cellular profiling of post mortem COVID-19 and normal lung tissues. Two distinct immunopathological reaction patterns were identified. One pattern showed high expression of interferon stimulated genes (ISGs) and cytokines, high viral loads and limited pulmonary damage, the other pattern showed severely damaged lungs, low ISGs, low viral loads and abundant immune infiltrates. Distinct patterns of pulmonary COVID-19 immune responses correlated to hospitalization time and may guide treatment and vaccination approaches.

scholarly journals Two distinct immunopathological profiles in lungs of lethal COVID-19

2020 ◽  
Author(s):  
Ronny Nienhold ◽  
Yari Ciani ◽  
Viktor H. Koelzer ◽  
Alexandar Tzankov ◽  
Jasmin D. Haslbauer ◽  
...  
Keyword(s):  
Immune Responses ◽  
The Other ◽  
High Expression ◽  
Normal Lung ◽  
Post Mortem ◽  
Viral Loads ◽  
Interferon Stimulated Genes ◽  
Hospitalization Time ◽  
Pulmonary Damage ◽  
Reaction Patterns

AbstractImmune responses in lungs of Coronavirus Disease 2019 (COVID-19) are poorly characterized. We conducted transcriptomic, histologic and cellular profiling of post mortem COVID-19 and normal lung tissues. Two distinct immunopathological reaction patterns were identified. One pattern showed high expression of interferon stimulated genes (ISGs) and cytokines, high viral loads and limited pulmonary damage, the other pattern showed severely damaged lungs, low ISGs, low viral loads and abundant immune infiltrates. Distinct patterns of pulmonary COVID-19 immune responses correlated to hospitalization time and may guide treatment and vaccination approaches.

scholarly journals Two distinct immunopathological profiles in autopsy lungs of COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ronny Nienhold ◽  
Yari Ciani ◽  
Viktor H. Koelzer ◽  
Alexandar Tzankov ◽  
Jasmin D. Haslbauer ◽  
...  
Keyword(s):  
Immune Responses ◽  
Normal Lung ◽  
Pathogenic Factor ◽  
Blood Biomarkers ◽  
Viral Loads ◽  
Interferon Stimulated Genes ◽  
Immune Mediated ◽  
Pulmonary Damage ◽  
Reaction Patterns ◽  
Local Expression

Abstract Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

scholarly journals High expression of hypoxia inducible factor 1α related with acquired resistant to EGFR tyrosine kinase inhibitors in NSCLC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian Jin ◽  
Feihua Huang ◽  
Xianrong Xu ◽  
Haidong He ◽  
Yingqing Zhang
Keyword(s):  
First Generation ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Hypoxia Inducible Factor ◽  
High Expression ◽  
Normal Lung ◽  
Nsclc Tissue ◽  
T790m Mutation ◽  
Level Group ◽  
Egfr Tkis

AbstractThe acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance.

scholarly journals VIII. On the descending degenerations which follow lesions of the gyrus marginalis and gyrus fornicatus in monkeys

1889 ◽  
Vol 180 ◽  
pp. 331-354
Keyword(s):  
The Other ◽  
Post Mortem ◽  
Cerebral Lesions ◽  
Series Of Experiments ◽  
The Government ◽  
Government Grant

The following paper contains the record of an investigation into the degenerations which follow lesions of the gyrus marginalis and gyrus fornicatus in Monkeys. The work has been carried on under my direction by Mr. France, with the aid of a grant from the Government Grant Fund, and represents part of a long investigation into the degenerations which follow artificially produced cerebral lesions, the material for which has been furnished by cases operated upon in conjunction respectively with Professor V. Horsley and Dr. Sanger Brown. These cases and the physiological results of the operations have already been published in the ‘Philosophical Transactions.’ The experiments here dealt with, twelve in number, comprise only the lesions of the gyrus marginalis and gyrus fornicatus, and, with one exception (case 12), are taken from the series of experiments performed in conjunction with Mr. Horsley. Of the twelve cases, six were of removal, or attempted removal, of the gyrus marginalis, and six of removal, or attempted removal, of the gyrus fornicatus. But in only one or two instances was the lesion, as determined by post-mortem examination, exactly limited to the convolution which it was attempted to remove, for in most cases the adjacent gyrus was to a certain extent involved in the injury. This was especially the case when removal of the gyrus fornicatus had been attempted, on account of its deep situation, and the difficulty of getting at it without some manipulation of the superjacent gyrus. Nevertheless, the removal of one or the other gyrus was sufficiently complete in all the cases here selected to produce characteristic symptoms and characteristic descending degenerations.

Immune responses of Texel sheep to excretory/secretory products of adult Haemonchus contortus

Parasitology ◽  
1994 ◽  
Vol 108 (3) ◽  
pp. 351-357 ◽  
Author(s):  
H. D. F. H. Schallig ◽  
M. A. W. van Leeuwen ◽  
W. M. L. Hendrikx
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Haemonchus Contortus ◽  
Lymphocyte Proliferation ◽  
The Other ◽  
Proliferation Index ◽  
Serum Samples ◽  
Immunoblotting Analysis ◽  
Molecular Weights ◽  
Secretory Products

SUMMARYThe excretory/secretory (E/S) products of adult Haemonchus contortus comprise of at least 15 polypeptides with molecular weights ranging from 10 to > 100 kDa. These E/S products induce an immune response in infected Texel sheep, as demonstrated by specific IgGI levels and a significant lymphocyte proliferation index. Moreover, immunoblotting analysis revealed that sera of primary H. contortus-infected sheep specifically recognize a 24 kDa E/S product. In addition, sera of challenged sheep react strongly with a 15 kDa E/S product. The other E/S products of H. contortus showed immunoreactivity with serum samples of Haemonchus-infected sheep as well as with samples of sheep harbouring other trichostrongylid infections. These cross-reacting epitopes are the main cause of the lack of specificity of an E/S material- based ELISA. This ELISA can differentiate Haemonchus infections from Nematodirus battus infections, but not from Ostertagia circumcincta or Trichostrongylus colubriformis infections.

scholarly journals Trypanosoma cruzi meningoencephalitis and myocarditis in a patient with acquired immunodeficiency syndrome

1993 ◽  
Vol 35 (2) ◽  
pp. 205-208 ◽  
Author(s):  
Ademir Rocha ◽  
Marcelo S. Ferreira ◽  
Sergio A. Nishioka ◽  
Marcos Silva ◽  
Marcius K. N. Burgarelli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Differential Diagnosis ◽  
Chagas Disease ◽  
Acquired Immunodeficiency Syndrome ◽  
The Other ◽  
Post Mortem ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Male Heterosexual

We report the case of a 52-year-old male heterosexual patient with acquired immunodeficiency syndrome (AIDS) and reactivation of Chagas' disease manifested by meningoencephalitis and myocarditis, diagnosed post-mortem. Unexplained reactivation of Chagas' disease should be included among the diagnostic criteria of AIDS in human immunodeficiency virus positive patients. On the other hand, AIDS should be considered in the differential diagnosis of patients with unexplained reactivation of Chagas' disease.

scholarly journals In depth characterization of vaccine breakthrough infections with SARS-CoV-2 among healthcare workers of a Dutch academic medical center

2021 ◽  
Author(s):  
Lidewij W Rümke ◽  
Femke C Groenveld ◽  
Yvonne M G van Os ◽  
Patrique Praest ◽  
Anniek A N Tanja ◽  
...  
Keyword(s):  
Immune Responses ◽  
Healthcare Workers ◽  
Medical Center ◽  
Academic Medical Center ◽  
Risk Exposure ◽  
Live Virus ◽  
Viral Loads ◽  
Academic Medical ◽  
T Cell Immune Responses

Abstract SARS-CoV-2 infection after COVID-19 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch healthcare workers ≥14 days post final dose of vaccination with either BNT162b2, mRNA-1273 or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.

Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Ke-Qin Xin ◽  
Yuka Hoshino ◽  
Yoshihiko Toda ◽  
Shizunobu Igimi ◽  
Yoshitsugu Kojima ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lactococcus Lactis ◽  
Potential Role ◽  
Protective Efficacy ◽  
Oral Immunization ◽  
Vaccine Strategy ◽  
Regional Lymph Nodes ◽  
Viral Loads ◽  
Recombinant Lactococcus Lactis ◽  
Further Development

Abstract This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

CONGENITAL CYSTIC ADENOMATOID MALFORMATION OF THE LUNG

PEDIATRICS ◽  
1962 ◽  
Vol 30 (5) ◽  
pp. 759-768
Author(s):  
John Kwittken ◽  
Leopold Reiner
Keyword(s):  
Special Form ◽  
The Other ◽  
Normal Lung ◽  
Congenital Cystic Adenomatoid Malformation ◽  
Elastic Tissue ◽  
Alveolar Cell ◽  
Bronchial Wall ◽  
Cystic Lung ◽  
Cystic Adenomatoid Malformation ◽  
Pulmonary Adenomatosis

Two new cases of congenital cystic adenomatoid malformation of the lung are reported. Both patients died shortly after birth, one at 36 hours and the other on the tenth postnatal day. Cystic adenomatoid malformation is a special form of cystic lung disease characterized by large and small cysts lined variably by a bronchial-type (respiratory) and by cuboidal epithelium. In spite of the bronchial-type epithelium in some of the cysts, bronchial wall elements such as cartilage and mucoserous glands were not demonstrated. There was much elastic tissue in these cysts, of a degree having no counterpart in normal lung. These observations together with the topographic interposition of the cysts with normal appearing alveolar structures suggest a developmental malformation affecting those segments of the lungs normally destined to become the terminal bronchioles, respiratory bronchioles, and alveolar ducts. In one case, groups of alveoli were lined with a tall mucogenic epithelium morphologically resembling that seen in pulmonary adenomatosis of man and jaagsiekte of sheep. The finding is considered the result of alveolar cell metaplasia.

Gamma-interferon inducible lysosomal thiolreductase (GILT) effect on breast tumor microenvironment through regulating CXCR6/CXCL16 axis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15081-e15081
Author(s):  
YinJiao Fei ◽  
MingXing Liang ◽  
Lei Li ◽  
Yuxin Song ◽  
Zhen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Western Blot ◽  
Cell Line ◽  
Gamma Interferon ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Axillary Lymph ◽  
Potential Biomarker

e15081 Background: Gamma-interferon Inducible Lysosomal Thiolreductase (GILT) is constitutively expressed in most antigens endocytosed by antigen presenting cells (APCs), and its function is to catalyze the reduction of disulfide (S-S) bonds in protein substrates. The cytokine CXCL16 is one of the only two known plasma membrane chemokines which induces chemotaxis of activated T cells and bone marrow plasma cells in tumor microenvironment. It contains a free end folded by two sulfur bonds and therefore could also be a zymolyte of GILT. Previous studies found that specific receptor of CXCL16, CXCR6, was significantly overexpressed in breast cancer tissues and metastatic axillary lymph nodes. We suppose whether CXCR6/CXCL16 axis is regulated by GILT and affect tumor microenvironment, thereby eliciting specific anti-tumor immune responses in breast cancer (BC). Methods: GILT expression in BC was evaluated using publicly available data from The Cancer Genome Atlas (TCGA). GILT gene was analyzed in UALCAN ( http://ualcan.path.uab.edu/analysis-prot.html ) . In vitro, Immunohistochemistry (IHC) was conducted to examine the location and relation of GILT and CXCR6. Gene Set Enrichment Analysis (GSEA) was performed to mine the biological pathways involved in BC related GILT regulatory network. The expression of GILT at protein and RNA levels were detected by Western Blot and RT-PCR assay. Overexpression and knockdown of GILT in BC cell lines was carried out to further analyzed the correlation between GILT and CXCL16/CXCR6. Results: TCGA database showed that GILT expression was increased in the stroma of BC compared with normal, and was correlated to shorter BC overall survival. GSEA suggested that the expression of GILT was associated with chemotactic factors. Pearson analysis and IHC showed GILT had a strong correlation with CXCL16/CXCR6 axis in the aspect of angiogenesis and immunity. qRT-PCR and Western Blot assay also revealed that GILT had high expression in BC. Besides, patients with high expression of GILT in IHC simultaneously showed high immunoreactive to macrophage markers, which was related to neovascularization and anti-tumor immune responses. Compared with the normal breast cell line MCF-10A, GILT protein had high expression in Hs578T and low expression in MDA-MB-231 cell line. GILT was overexpressed in MDA-MB-231 and knockdown in Hs578T. Result showed that high level GILT promoted the production of CXCL16/CXCR6,while GILT siRNA knockdown inhibited the production of CXCL16/CXCR6. Conclusions: GILT could catalyze CXCL16 in BC, function as a key mechanism to affect tumor microenvironment through CXCR6/CXCL16 pathway. GILT-activated CXCL16 levels showed a strong connection with unfavorable outcomes in BC, which could be a potential biomarker of prognosis and a novel therapeutic target.

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