Profiling system-wide variations and similarities between rheumatic heart disease and acute rheumatic fever–A pilot analysis.

Autor: Guttapadu, Ranjitha, Prakash, Nandini, M, Alka, Chatterjee, Ritika, S, Mahantesh, M, Jayranganath, Sastry, Usha MK, Subramanyam, Jayshree Rudrapatna, Chakravortty, Dipshikha, R, Kalpana S., Chandra, Nagasuma
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Zdroj: PLoS Neglected Tropical Diseases; 4/5/2023, Vol. 18 Issue 4, p1-19, 19p
Abstrakt: Rheumatic heart disease (RHD) continues to affect developing countries with low income due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis common to both the diseases and that of progression from its prequel disease state, acute rheumatic fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, in this pilot study, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis approach, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated, while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be linked with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found a significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited Natural Killer cell gene signatures reflected the drivers of the inflammatory process typical to both disease conditions. Author summary: Rheumatic Heart Disease (RHD), a neglected disease in developing countries that lack access to advanced health care, continues to plague many children and adolescents. While it is known that Acute Rheumatic Fever (ARF) plays a causal role in RHD, only a subset of ARF patients progress to RHD. Understanding the transcriptome level differences between these two disease states would aid in understanding the progression of the prequel state and stage an intervention at an appropriate time to avert fatal consequences. This pilot study aimed to understand the pathway-level perturbations caused in individuals with either disease condition and explore their similarities and differences. Using sensitive network mining approaches and transcriptomics, we identified differentially expressed genes (DEGs) in highly perturbed condition-specific protein-protein interactions networks unique to RHD compared to ARF by filtering out DEGs altered with respect to healthy and clinical controls. We also report differences in clinical parameters in the disease states. The study shows great potential in developing tools such as predictive biomarkers to study the progression of RHD while also unraveling novel pathway-level perturbations. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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