Integrated transcriptomic and proteomic analysis reveals innate and adaptive immune dynamics in systemic autoinflammatory diseases

Résumé fourni par la source

Systemic autoinflammatory diseases (SAIDs) are a diverse group of rare disorders with partially overlapping clinical features. However, their genetic makeup and treatment responses vary widely. Although inflammasome dysregulation is central to many SAIDs, recent studies suggest that additional immune pathways may also contribute to disease activity. We integrated bulk transcriptomic and plasma proteomic data from SAID patients and negative controls, generated using the NovaSeq 6000 and SomaScan platform, respectively. We assessed the expression patterns of four inflammation-related genes (IL1B, IL6, IL18 and BLNK) and evaluated differential expression between patients and controls, and between initial and follow-up samples. We constructed protein-protein interaction (PPI) networks of the transcripts and proteins, then performed a functional enrichment analysis to identify gene sets that were significantly enriched in each PPI network. Transcriptomic profiling identified 1,805 differentially expressed transcripts. BLNK showed significant inverse correlations with IL1B and IL18, whereas BLNK and IL6 were correlated with B-cell proportions. Among the top 50 upregulated transcripts, three enriched groups were identified: associated with secretory granules, haemoglobin complexes and adaptive immune responses. Differential proteomic analysis identified 1217 differentially abundant proteins; the top 50 upregulated proteins were categorised into four groups related to complement activation, the acute-phase response, neutrophil migration and extracellular matrix organisation. Finally, we observed transcriptomic and proteomic expression changes during follow-up. Our analyses reveal the diverse inflammatory signatures observed across patients. These findings underscore the complexity of SAID pathophysiology and could help refine hypotheses regarding disease mechanisms and patient stratification. Systemic autoinflammatory diseases (SAIDs) are rare disorders that occur when the immune system becomes overactive. This results in recurring symptoms such as fever, inflammation and joint pain. These diseases are difficult to diagnose and treat because patients often exhibit overlapping symptoms, and their genetic backgrounds and responses vary widely. Rather than focusing on individual genes or markers, we examined patterns of gene activity and blood proteins in a large cohort of patients. Our research identified patterns of gene activity and protein levels shared across SAIDs and associated with innate and adaptive immune-related genes and proteins, including B-cell markers. These findings demonstrate the complexity of the SAID mechanism and will help to guide future studies of patient heterogeneity and treatment responses. van Wijngaarden et al., integrate bulk transcriptomic and plasma proteomic data from patients with systemic autoinflammatory diseases and controls to characterise inflammatory pathways and monitor molecular changes over time. They identify distinct transcriptomic and proteomic inflammatory signatures, including associations between BLNK, cytokine-related genes and immune cell populations, revealing disease heterogeneity and molecular changes during follow-up.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.