Identification of Immune‐Related Lactylation Genes in Rheumatoid Arthritis With Atherosclerosis: A Comprehensive Analysis Using Bulk and Single‐Cell RNA Sequencing Data

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Abstract
Background: Growing evidence demonstrates that rheumatoid arthritis (RA), a chronic autoimmune disease characterized by joint inflammation and immune system dysfunction, can significantly accelerate the progression of atherosclerosis (AS). Studies have revealed that patients with RA and AS share numerous common features in terms of immune dysregulation and metabolic alterations, with abnormalities in lactate metabolism being particularly prominent. However, the role of lactate and its associated protein modification—lactylation—in the pathogenesis of RA‐related AS remains unclear. The primary objective of this study is to comprehensively investigate lactylation‐related genes as potential diagnostic markers for patients with concurrent RA and AS. Methods: We identified the core genes associated with lactylation by integrating and analyzing two disease‐related datasets: a RA dataset (GSE89408) and an AS dataset (GSE43292) from the GEO database. Through comprehensive analysis, we examined the functions associated with the hub genes and investigated the correlation between their expression levels and immune infiltration. Additionally, we explored the lactylation scores of different immune cells using single‐cell data. Results: We identified four lactylation‐related hub genes (SMARCC2, CCNA2, NUP50, and GATAD2B) highly associated with concurrent RA and AS, which showed high diagnostic potential (area under the curve [AUC] > 0.88). Further analysis revealed that these four hub genes were significantly correlated with the level of immune cell infiltration. To better understand the relationship between lactylation and immune cells, we analyzed single‐cell sequencing data, which demonstrated significant differences in lactylation scores across various types of immune cells. Conclusions: These findings highlight lactylation‐related genes as promising diagnostic markers and provide insights into shared pathogenic mechanisms of RA and AS.
Funding Information
  • National Natural Science Foundation of China (82571999)

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