Regulation of lncRNA NUTM2A-AS1 and CCR3 in the Clinical Response to a Plant-Based Diet in Rheumatoid Arthritis: A Pilot Study

<b>Background/Objectives:</b> RA is a chronic autoimmune disease characterized by systemic inflammation and progressive joint damage. Plant-based dietary interventions have recently emerged as complementary anti-inflammatory therapy for active RA. However, the molecular anti-inflammatory mechanisms of plant-based dietary patterns in these patients are still poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of inflammation in chronic diseases. Thus, this study aimed to evaluate the expression of lncRNAs and inflammatory genes in relation to the clinical response to following a plant-based dietary intervention in patients with active RA. <b>Methods:</b> A two-phase whole-blood gene expression analysis was conducted for patients with active RA before and after a 14-day plant-based dietary intervention. In the discovery phase, seven patients showing the greatest reduction in disease activity (DAS28-CRP) were selected, and the expression of 84 inflammatory genes and 84 lncRNAs was analyzed using RT² Profiler PCR Array platforms. In the validation phase, by adding 14 patients, we assessed 21 participants. <b>Results:</b> NUTM2A-AS1 was the only significantly overexpressed lncRNA in the discovery phase (<i>p</i> = 0.0435), while CCR3 was the only inflammatory gene showing significant expression change (<i>p</i> = 0.0156). In the validation phase, both NUTM2A-AS1 and CCR3 maintained the same pattern of overexpression, confirming their modulation after the 14-day plant-based dietary intervention (<i>p</i> = 0.0131 and <i>p</i> < 0.001, respectively). <b>Conclusions</b>: This study showed that a 14-day plant-based diet was sufficient to modify the inflammatory circuits in patients with active RA, suggesting a potential dietary-mediated inflammatory modulation mechanism involving NUTM2A-AS1 and CCR3. Further studies are required to validate new hypotheses on the biological significance of the regulation of these transcripts and its clinical implications in RA management.