Radhakrishna Uppala, Ratnamala Uppala, Jhala Devendrasinh D, Uppala Lavanya V, Vedangi Aaren, Saiyed Nazia, Shah Sushma R, Patel Maulikkumar, Rawal Rakesh M, Mazza Tommaso, Jemec Gregor B E, Mazzoccoli Gianluigi, Damiani Giovanni
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India.
Front Immunol. 2024 Nov 26;15:1475424. doi: 10.3389/fimmu.2024.1475424. eCollection 2024.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects hair follicles in areas with apocrine sweat glands, such as the underarms, groin, and buttocks. The pathogenesis of HS is not fully understood, but considering the key role played by the biological clock in the control of immune/inflammatory processes the derangement of circadian and ultradian pathways could be hypothesized.
We analyzed genome-wide DNA methylation patterns in peripheral blood from 24 HS cases and 24 controls using the Infinium HumanMethylation450 BeadChip array (Illumina), followed by bioinformatics and statistical analyses.
We found that several circadian and ultradian genes were differentially methylated in HS patients, predominantly exhibiting hypomethylation. These genes were enriched in pathways such as MAPK and WNT cascades, acute phase response, cytokine release, inflammation, innate immune response, xenobiotic detoxification, and oxidative stress response.
Altered DNA methylation patterns of genes related to circadian and ultradian pathways could contribute to immune system derangement and inflammatory processes chronicization in addition to other comorbidities hallmarking HS onset and progression, at the same time representing possible druggable targets.
化脓性汗腺炎（HS）是一种慢性炎症性皮肤病，影响顶泌汗腺分布区域的毛囊，如腋窝、腹股沟和臀部。HS的发病机制尚未完全明确，但考虑到生物钟在免疫/炎症过程控制中发挥的关键作用，可以推测昼夜节律和超日节律途径出现紊乱。
我们使用Illumina Infinium HumanMethylation450 BeadChip芯片对24例HS患者和24例对照者外周血中的全基因组DNA甲基化模式进行分析，随后进行生物信息学和统计分析。
我们发现，HS患者中几个昼夜节律和超日节律基因存在差异甲基化，主要表现为低甲基化。这些基因富集于丝裂原活化蛋白激酶（MAPK）和WNT级联反应、急性期反应、细胞因子释放、炎症、固有免疫反应、外源性物质解毒及氧化应激反应等途径。
除了标志HS发病和进展的其他合并症外，昼夜节律和超日节律途径相关基因的DNA甲基化模式改变可能导致免疫系统紊乱和炎症过程慢性化，同时也代表了可能的药物作用靶点。
