Comprehensive analysis of immunoglobulin and clinical variables identifies functional linkages and diagnostic indicators associated with Behcet's disease patients receiving immunomodulatory treatment.

Comprehensive analysis of immunoglobulin and clinical variables identifies functional linkages and diagnostic indicators associated with Behcet's disease patients receiving immunomodulatory treatment.
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对免疫球蛋白和临床变量的综合分析确定了与接受免疫调节治疗的白塞病患者相关的功能联系和诊断指标

DOI:
10.1186/s12865-021-00403-1
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发表时间:
2021-02-22
期刊:
影响因子:
3
通讯作者:
Li Y
Li Y
中科院分区:
医学4区
文献类型:
--
作者:
Cheng L;Li Y;Wu Z;Li L;Liu C;Liu J;Dai J;Zheng W;Zhang F;Tang L;Yu X;Li Y

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白塞病(BD)是一种复发性全身血管自身免疫性/炎症性疾病。尽管人们对BD进行了大量的研究,但几乎没有独特的实验室标记物被发现有助于BD的诊断,其发病机制也很大程度上是未知的。这项工作的目的是通过相关性分析来探索不同临床变量之间的相互作用,以确定不同配对变量的功能联系与潜在的BD诊断生物标志物之间的关联。对66例健康人和63例BD患者的免疫球蛋白(Ig G、Ig G1-4、Ig A、Ig A1-2)及29项临床指标进行了检测。我们进行了一项全面的临床变量连锁分析,并根据健康对照组和未接受免疫调节治疗的BD患者和接受免疫调节治疗的BD患者所有变量之间的相关性,确定了生理、病理和药理学方面的联系。我们进一步计算了综合连锁分析得出的变量之间的相对变化,以便更好地应用于临床。对76名BD患者、30名健康对照、18名大动脉炎患者和18名ANCA相关脉管炎患者进行了验证。在这项研究中,在生理、病理和药物条件下,确定的变量在BD患者中被发现是协同作用的,而不是单独作用的。免疫和炎症可被皮质类固醇和免疫抑制剂抑制,对粒细胞、血小板和相关变量的综合分析可能提供对疾病活动性、血栓形成潜力和最终潜在的组织损伤的更全面的了解。我们发现BD患者的总蛋白/平均红细胞血红蛋白和总蛋白/平均红细胞血红蛋白水平、总蛋白/平均红细胞体积和血小板压积/单核细胞计数显著高于对照组(P < 0.05,在发现和验证组中),这有助于将BD患者与健康和血管炎对照组区分开来。BD患者的慢性贫血和总蛋白增加导致这些生物标志物水平升高,而血小板和单核细胞之间的相互作用可能与血管受累有关。所有这些结果表明,我们的方法在阐明发病机制和识别未来自身免疫性疾病的新生物标记物方面是有用的。网上版载有补充材料,可在10.1186/s12865-021-00403-1查阅。
Behcet’s disease (BD) is a relapsing systemic vascular autoimmune/inflammatory disease. Despite much effort to investigate BD, there are virtually no unique laboratory markers identified to help in the diagnosis of BD, and the pathogenesis is largely unknown. The aim of this work is to explore interactions between different clinical variables by correlation analysis to determine associations between the functional linkages of different paired variables and potential diagnostic biomarkers of BD. We measured the immunoglobulin proteome (IgG, IgG1–4, IgA, IgA1–2) and 29 clinical variables in 66 healthy controls and 63 patients with BD. We performed a comprehensive clinical variable linkage analysis and defined the physiological, pathological and pharmacological linkages based on the correlations of all variables in healthy controls and BD patients without and with immunomodulatory therapy. We further calculated relative changes between variables derived from comprehensive linkage analysis for better indications in the clinic. The potential indicators were validated in a validation set with 76 patients with BD, 30 healthy controls, 18 patients with Takayasu arteritis and 18 patients with ANCA-associated vasculitis. In this study, the variables identified were found to act in synergy rather than alone in BD patients under physiological, pathological and pharmacological conditions. Immunity and inflammation can be suppressed by corticosteroids and immunosuppressants, and integrative analysis of granulocytes, platelets and related variables is likely to provide a more comprehensive understanding of disease activity, thrombotic potential and ultimately potential tissue damage. We determined that total protein/mean corpuscular hemoglobin and total protein/mean corpuscular hemoglobin levels, total protein/mean corpuscular volume, and plateletcrit/monocyte counts were significantly increased in BD compared with controls (P < 0.05, in both the discovery and validation sets), which helped in distinguishing BD patients from healthy and vasculitis controls. Chronic anemia in BD combined with increased total protein contributed to higher levels of these biomarkers, and the interactions between platelets and monocytes may be linked to vascular involvement. All these results demonstrate the utility of our approach in elucidating the pathogenesis and in identifying novel biomarkers for autoimmune diseases in the future. The online version contains supplementary material available at 10.1186/s12865-021-00403-1.
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