Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.中文摘要艾滋病仍然是全世界最严重的公共卫生挑战, 尤其是对艾滋病免疫无应答者而言, 他们往往有更高的死亡率。由于中医药在促进患者免疫重建方面优势突出, 现已成为艾滋病免疫无应答者补充治疗的支柱之一。鉴于有效的中医药治疗基于精准的辨证, 探索艾滋病免疫重建不全中医证候分类的生物学依据备受青睐。在我们的研究中, 为了确定艾滋病免疫无应答者的中医证候分布规律, 首先在我国艾滋病高发区凉山州进行了流行病学调查。接着我们采用TMT-LC-MS/MS技术对典型中医证候脾肾阳虚证进行了蛋白组学研究, 筛选出62种差异表达蛋白。通过生物信息分析显示, 脾肾阳虚证中的差异表达蛋白主要与生物过程中的创伤反应和急性炎症反应等有关。通路富集主要集中在补体和凝血级联等方面。最后, 利用ELISA检测方法对脾肾阳虚证候特异性蛋白HP和S100A9进行验证, 最终将这两种证候特异性蛋白确认为脾肾阳虚证的生物标记物。这为艾滋病免疫无应答中医证候的特异性奠定了生物学和科学基础, 为深入了解中医证候, 开发更有效、更稳定的中医治疗提供了更多机会。.