From Home to Transcriptome: Comparing the Transcriptomic Profile of Induced Immune Response via Lipopolysaccharide Stimulation in homeRNA and Venous Blood

Remote blood sampling offers multiple advantages over traditional clinic-based blood sampling studies, including greater patient inclusion, more frequent sampling, and broader geographical reach. Combining remote blood sampling with transcriptomic analysis opens potential in translational applications for capturing acute and dynamic immune responses to various exposures. In this study, we establish the feasibility of homeRNA, a capillary blood collection and RNAlater-based stabilization kit, for use in downstream total RNA-sequencing applications via capturing a lipopolysaccharide (LPS)-induced inflammatory response. We also compared the baseline gene expression profiles and induced inflammatory response following LPS stimulation between homeRNA-stabilized samples and venous blood stabilized with RNAlater or PAXgene. We found that homeRNA was successfully able to capture an inflammatory response to LPS, specifically targeting various cytokines (e.g., IL6, IL12B, IL1B), chemokines (e.g., CCL3, CXCL10, CCL4), and other transcriptional factors in the toll-like receptor pathway, the primary pathway activated during LPS stimulation. Importantly, we also found that homeRNA captured a LPS-induced inflammatory response comparable to that of venous blood samples stabilized with either RNAlater or PAXgene. Overall, this work demonstrates that the homeRNA platform is compatible with downstream total RNA-sequencing analysis and can capture transcriptomic immune responses to a known stimulus which are analogous to results in traditional stabilized venous blood samples.与传统基于临床诊室的血液采样研究相比，远程血液采样具备多重显著优势，涵盖更广的患者纳入范围、更灵活的采样频次以及更广泛的地域覆盖能力。将远程血液采样与转录组分析相结合，可为捕捉各类暴露下的急性动态免疫应答提供转化应用潜力。本研究中，我们通过捕捉脂多糖（lipopolysaccharide, LPS）诱导的炎症应答，验证了homeRNA——一款兼具毛细血管采血与RNAlater稳定功能的试剂盒——可应用于下游总RNA测序的可行性。我们还对比了经homeRNA稳定的样本，与经RNAlater或PAXgene稳定的静脉血样本的基线基因表达谱，以及LPS刺激后诱导的炎症应答。研究结果显示，homeRNA可成功捕捉针对LPS的炎症应答，其靶向覆盖各类细胞因子（如IL6、IL12B、IL1B）、趋化因子（如CCL3、CXCL10、CCL4），以及LPS刺激过程中激活的核心通路——Toll样受体通路中的其他转录因子。尤为重要的是，我们还发现homeRNA所捕捉到的LPS诱导炎症应答，与经RNAlater或PAXgene稳定的静脉血样本所得结果相当。综上，本研究证实homeRNA平台可兼容下游总RNA测序分析，且能够捕捉针对已知刺激物的转录组免疫应答，其结果与传统稳定静脉血样本的检测结果一致。