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Profiling system-wide variations and similarities between Rheumatic Heart Disease and Acute Rheumatic Fever–A pilot analysis

Guttapadu, R and Prakash, N and M, A and Chatterjee, R and S, M and M, J and Sastry, UM and Subramanyam, JR and Chakravortty, D and R, KS and Chandra, N (2023) Profiling system-wide variations and similarities between Rheumatic Heart Disease and Acute Rheumatic Fever–A pilot analysis. In: PLoS neglected tropical diseases, 17 (4). e0011263.

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Official URL: https://doi.org/10.1371/journal.pntd.0011263


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. Copyright: © 2023 Guttapadu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Item Type: Journal Article
Publication: PLoS neglected tropical diseases
Publisher: NLM (Medline)
Additional Information: The copyright for this article belongs to the Authors.
Keywords: genetics; human; pilot study; poverty; rheumatic fever; rheumatic heart disease, Humans; Pilot Projects; Poverty; Rheumatic Fever; Rheumatic Heart Disease
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Microbiology & Cell Biology
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Division of Physical & Mathematical Sciences > Mathematics
Date Deposited: 22 May 2023 10:47
Last Modified: 22 May 2023 10:47
URI: https://eprints.iisc.ac.in/id/eprint/81560

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