scholarly journals Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles

2021 ◽  
Vol 22 (11) ◽  
pp. 5655
Author(s):  
Heather Jackson ◽  
Stephanie Menikou ◽  
Shea Hamilton ◽  
Andrew McArdle ◽  
Chisato Shimizu ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Disease Patient ◽  
Inflammatory Disorder ◽  
Comprehensive Picture ◽  
Clustering And Classification ◽  
Infection And Inflammation ◽  
Proteomic Responses

The aetiology of Kawasaki disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host ‘omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple ‘omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering, and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infections at the transcriptomic and proteomic levels through comparison of ‘omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both ‘omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both ‘omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition.

scholarly journals Kawasaki Disease patient stratification and pathway analysis based on host transcriptomic and proteomic profiles

2021 ◽  
Author(s):  
Heather Jackson ◽  
Stephanie Menikou ◽  
Shea Hamilton ◽  
Andrew McArdle ◽  
Chisato Shimizu ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Disease Patient ◽  
Inflammatory Disorder ◽  
Comprehensive Picture ◽  
Clustering And Classification ◽  
Infection And Inflammation ◽  
Proteomic Responses

The aetiology of Kawasaki Disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host 'omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple 'omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infection at the transcriptomic and proteomic levels through comparison of 'omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both 'omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both 'omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition.

scholarly journals 521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S326-S327
Author(s):  
Simone A Thair ◽  
Yudong He ◽  
Yehudit Hasin-Brumshtein ◽  
Suraj Sakaram ◽  
Rushika R Pandya ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Nk Cells ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Cell Types ◽  
Gene Signature ◽  
Gene Signatures ◽  
Similarities And Differences

Abstract Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

scholarly journals Kawasaki Disease and Allergic Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Po-Yu Huang ◽  
Ying-Hsien Huang ◽  
Mindy Ming-Huey Guo ◽  
Ling-Sai Chang ◽  
Ho-Chang Kuo
Keyword(s):  
Allergic Rhinitis ◽  
Kawasaki Disease ◽  
Viral Infections ◽  
Allergic Diseases ◽  
Epidemiological Studies ◽  
Unknown Etiology ◽  
Inflammatory Disorder ◽  
Term Care ◽  
Gamma Receptor ◽  
Acquired Heart Disease

Background: Kawasaki disease (KD) is an inflammatory disorder with an unknown etiology. It is the leading cause of acquired heart disease, which leads to coronary vasculitis among children. Studies of frequent manifestation of allergic diseases in children with KD have been the subject of mounting clinical interest. However, evidence supporting the association between KD and allergies has yet to be systematically reviewed.Methods: In this article, we reviewed current literature regarding the association between KD and allergic diseases. References for this review were identified through searches of PubMed, Cochrane, and Embase through the end of August 2020.Results: The results of the analyses of immune repertoire, clinical, and epidemiological studies have indicated some of the characteristics of infectious disease for KD. Although some allergic disorders, such as asthma, may be exacerbated by viral infections, allergies are typically caused by an allergen that triggers an immune response, with the potential involvement of type 2 inflammation and immune disturbances leading to tissue remodeling in genetically susceptible hosts. The effect of intravenous immunoglobulin is multi-faceted and results in a decrease in activating Fc gamma receptor IIA and an increase in anti-inflammatory eosinophils. The findings from this review demonstrate that children who have suffered from KD are more likely to have allergic rhinitis than the general population and their siblings, a condition that lasts until the age of 17. When followed up as teenagers and adults, children with KD are more likely to develop urticaria.Conclusions: This review supports that allergic diseases, such as allergic rhinitis, have been demonstrated to increase following KD. Therefore, the importance of allergic diseases in patients with KD should be emphasized in long-term care. Interventions that include strategies for managing allergies in children with KD would be beneficial.

scholarly journals CASP5 and CR1 as Potential Biomarkers for Kawasaki Disease: An Integrated Bioinformatics-Experimental Study

2021 ◽  
Author(s):  
Yazdan Rahmati ◽  
Hasan Mollanoori ◽  
Sajad Najafi ◽  
Sajad Esmaeili ◽  
Mohammad-Reza Alivand
Keyword(s):  
Kawasaki Disease ◽  
Mononuclear Cells ◽  
Viral Infections ◽  
Unknown Etiology ◽  
Inflammatory Disorder ◽  
Rt Pcr ◽  
Peripheral Blood Mononuclear ◽  
Expression Arrays ◽  
Limma Package ◽  
Network Modules

Abstract Kawasaki disease (KD) is a pediatric inflammatory disorder causes coronary artery complications. The disease overlapping manifestations with a set of symptomatically like diseases such as bacterial and viral infections, juvenile idiopathic arthritis, Henoch-Schönlein purpura, infection of unknown etiology, group-A streptococcal and adenoviral infections, and incomplete KD could lead to misdiagnosis of the disease. In the present study, we applied weighted gene co-expression network analysis (WGCNA) to identify network modules of co-expressed genes in GSE73464 and also, limma package was used to identify the differentially expressed genes (DEGs) in KD expression arrays composed of GSE73464, GSE18606, GSE109351, and GSE68004. By merging the results of WGCNA and limma, we detected hub genes. Then, analyzed the peripheral blood mononuclear cells (PBMCs) of 16 patients and 8 control subjects using Real-Time Polymerase Chain Reaction (RT-PCR) to evaluate the previous results. We assessed the diagnostic potency of the screened genes by plotting the area under curve (AUC). We finally identified 2 genes CASP5 and CR1 which were shown to potentially discriminate KD from other similar diseases and also from healthy people. The results of RT-PCR and AUC confirmed the diagnostic potentials of two suggested biomarkers for KD.

scholarly journals CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yazdan Rahmati ◽  
Hasan Mollanoori ◽  
Sajad Najafi ◽  
Sajjad Esmaeili ◽  
Mohammad Reza Alivand
Keyword(s):  
Kawasaki Disease ◽  
Mononuclear Cells ◽  
Viral Infections ◽  
Unknown Etiology ◽  
Inflammatory Disorder ◽  
Rt Pcr ◽  
Peripheral Blood Mononuclear ◽  
Expression Arrays ◽  
Limma Package ◽  
Network Modules

Abstract Background Kawasaki disease (KD) is a pediatric inflammatory disorder causes coronary artery complications. The disease overlapping manifestations with a set of symptomatically like diseases such as bacterial and viral infections, juvenile idiopathic arthritis, Henoch-Schönlein purpura, infection of unknown etiology, group-A streptococcal and adenoviral infections, and incomplete KD could lead to misdiagnosis of the disease. Methods In the present study, we applied weighted gene co-expression network analysis (WGCNA) to identify network modules of co-expressed genes in GSE73464 and also, limma package was used to identify the differentially expressed genes (DEGs) in KD expression arrays composed of GSE73464, GSE18606, GSE109351, and GSE68004. By merging the results of WGCNA and limma, we detected hub genes. Then, analyzed the peripheral blood mononuclear cells (PBMCs) of 16 patients and 8 control subjects using Real-Time Polymerase Chain Reaction (RT-PCR) to evaluate the previous results. Results We assessed the diagnostic potency of the screened genes by plotting the area under curve (AUC). We finally identified 2 genes CASP5(Caspase 5) and CR1(Complement C3b/C4b Receptor 1) which were shown to potentially discriminate KD from other similar diseases and also from healthy people. Conclusions The results of RT-PCR and AUC confirmed the diagnostic potentials of two suggested biomarkers for KD.

scholarly journals Incidental Diagnosis of Anomalous Right Coronary Artery Originating from the Opposite Sinus, in a Kawasaki Disease Patient

2021 ◽  
Vol 71 (3) ◽  
pp. 199-201
Author(s):  
Yuiko Suzuki ◽  
Tetsuro Tamai ◽  
Shuhei Takahashi ◽  
Akiho Ueda ◽  
Rena Okada ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Right Coronary Artery ◽  
Disease Patient ◽  
Kawasaki Disease Patient ◽  
Incidental Diagnosis

scholarly journals Association between Kawasaki disease and acute respiratory viral infections

2009 ◽  
Vol 52 (11) ◽  
pp. 1241 ◽  
Author(s):  
Eun Young Cho ◽  
Byung Wook Eun ◽  
Nam Hee Kim ◽  
Jina Lee ◽  
Eun Hwa Choi ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Viral Infections ◽  
Respiratory Viral Infections

Abstract 193: Hemophagocytic lymphohistiocytosis following kawasaki disease:Differential Diagnosis in IVIG Refractory Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Hyun Ok Jun ◽  
Eun Kyung Cho ◽  
Jeong Jin Yu ◽  
So Yeon Kang ◽  
Chang Deok Seo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Coronary Artery ◽  
Kawasaki Disease ◽  
Skin Rash ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Clinical Symptoms ◽  
Early Recognition ◽  
Cervical Lymphadenopathy ◽  
Inflammatory Disorder ◽  
Laboratory Findings

Introduction: Hemophagocytic lymphohistiocytosis(HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. Thus, both HLH and Kawasaki disease(KD) are characterized by prolonged fever, and are diagnosed by a clinical and laboratory scoring system, concurrent manifestation of HLH and KD has been described in the literature. We describe two cases of children who diagnosed as KD initially, but after intravenous gamma globulin(IVIG) failed to produce clinical response, were found to have HLH. Case report: A 3-year-old boy who had previous KD history 5 months ago was admitted for 9day fever and skin rash. His symptoms were fulfilled KD criteria, and echocardiography showed dilated right coronary artery of 4.2mm. He was treated with 2 cycles of IVIG until fever subsided. However, 2 days later, he got fever again and cytopenia(Hb<9.0), hypertriglyceridemia, high level of ferritin was shown and had splenomegaly on physical examination. In the suspicion of HLH, bone marrow biopsy was done and revealed hemophagocytosis, consistent with HLH. A second case of 11-month-old boy admitted for 8-day fever with Kawasaki feature. Although, he showed incomplete feature(fever, skin rash, conjunctival injection, cervical lymphadenopathy), echocardiography showed dilated left main coronary artery(3.5mm) and treated with IVIG. However, 2days after IVIG administration, he was still pyrexial. The laboratory findings fulfilled 5 diagnostic criteria of HLH; bicytopenia(anemia, thrombocytopenia), hypofibrinogenemia, hyperferritinemia, hemophagocytosis in bone marrow, raised level of soluble IL-2 receptor. In both cases, the patients treated according to the HLH protocol 2004, and after that clinical symptoms and laboratory findings were improved. Several causes of febrile illness, EBV, CMV, rubella, parvo-viral infection, for example, were excluded. Comment: There is considerable overlap between the clinical syndromes of KD and HLH and early recognition and treatment of these two disease entity is imperative to avoid fatal outcomes in severe cases. Thus, these should both be considered and excluded in any child with unremitting fever and rash.

scholarly journals Interrelationships of Interferon and Immunity During Viral Infections

1970 ◽  
Vol 56 (1) ◽  
pp. 212-226 ◽  
Author(s):  
Lowell A. Glasgow
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Host Resistance ◽  
Host Response ◽  
Viral Infections ◽  
Cell Interaction ◽  
Relative Importance ◽  
Host Interaction ◽  
Interferon Responses

Interferon is one determinant of host resistance. The immune responses, cellular or humoral, are other components. Cell-mediated responses appear to be involved in host resistance to certain viral infections, particularly the herpesvirus group and vaccinia virus. It is suggested that immune and interferon responses may complement one another and contribute to host resistance. The relative importance of each component depends upon the virus-host interaction. Finally, evidence has been presented which suggests that production of interferon as a result of antigen-sensitized cell interaction may further link these two components of the host response.

Sign in / Sign up

Export Citation Format

Share Document