Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
Department of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Immunol. 2024 Feb 1;15:1288187. doi: 10.3389/fimmu.2024.1288187. eCollection 2024.
This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.
ClinicalTrials.gov, Identifier: NCT05045820.
本研究旨在全面分析处于稳定状态（StSt）的镰状细胞病（SCD）患者与健康对照者（HCs）的炎症和自身免疫特征，以探讨 SCD 的发病机制及其对患者健康的影响。
研究队列包括 2021 年 7 月至 2023 年 4 月期间入组的 40 名 SCD 患者和 23 名 HCs。与 HCs 相比，SCD 患者的白细胞（WBC）计数升高，血液学指标改变。采用多重免疫分析法分析这些 SCD 患者和 HCs 的血浆样本中的 80 种炎症细胞因子/趋化因子/生长因子。
SCD 患者的 35 种分析物的血浆水平显著升高，其中 HGF、IL-18、IP-10 和 MCP-2 是受影响最显著的分析物。此外，自身抗体谱也发生改变，SCD 患者的抗 SSA/Ro60、抗核糖体 P、抗髓过氧化物酶（MPO）和抗 PM/Scl-100 水平升高。流式细胞术分析显示 SCD 患者红细胞（RBC）/网织红细胞-白细胞聚集体率升高，主要涉及单核细胞。
相关性分析鉴定了炎症介质水平、自身抗体、RBC/网织红细胞-白细胞聚集体、临床实验室检测结果与疼痛危象/敏感性之间的相关性，提示这些因素之间存在复杂的相互作用。这些发现强调了特定生物标志物和治疗靶点的潜在重要性，这些标志物和靶点可能为未来针对 SCD 独特挑战的研究和临床干预提供有价值的信息。此外，血管阻塞性危象（VOC）/疼痛/敏感性与炎症/免疫失调之间的相关性为 SCD 的发病机制提供了有价值的见解，并可能导致更有针对性和有效的治疗策略。
ClinicalTrials.gov，标识符：NCT05045820。
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