Classical and lectin complement pathways and markers of inflammation for investigation of susceptibility to infections among healthy older adults
Classical and lectin complement pathways and markers of inflammation for investigation of susceptibility to infections among healthy older adults
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DOI：
10.1186/s12979-020-00189-7
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发表时间：
2020-06-10
影响因子：
7.9
通讯作者：
Nahm, Moon H.
中科院分区：
文献类型：
--
作者：
LaFon, David C.;Thiel, Steffen;Nahm, Moon H.
背景：人们越来越多地认识到老年人慢性低水平炎症或“炎症”的重要性。先天免疫反应和宿主-细菌相互作用被认为是炎症的关键因素。炎性细胞因子IL-6和补体蛋白C1q已被确定为虚弱和衰老相关疾病发生的生物标志物。老年人也容易感染肺炎链球菌的血清型感染，这种感染结合了凝集素补体途径的一种成分--无花果-2，而低无花果-2水平可能与这种易感性有关。方法本研究的目的是评估补体途径成分和老年人炎症的生物标志物，以探讨可能解释该人群感染易感性的潜在先天免疫机制。我们在健康的老年人和年轻人之间比较了炎症标志物以及经典和凝集素补充途径的成分/活性。我们假设老年人会有更高水平的炎症标志物和C1q，以及更低水平的凝集素途径成分。年龄较大(=70岁)和较年轻(19-54岁)、没有明显吸烟史或慢性疾病的成年人有资格参加。比较两组间炎症标志物(IL-6、肿瘤坏死因子-α、C反应蛋白)、经典补体途径活性(CH50)、蛋白水平(C1q、C3、C4)和凝集素途径(MBL水平/活性、CL-L1、MASP1/2/3、MAP44、MAP19、H/M/L-无花果)。结果老年患者IL-6和肿瘤坏死因子-α水平明显高于正常老年人。在老年人和年轻人之间，凝集素途径成分没有显著差异。出乎意料的是，在未经调整和调整后的分析中，年轻组的平均C1q显著更高。种族和C1q水平之间也有显著的关联，但这种关联并不能完全解释观察到的年龄组之间的差异。结论：我们没有观察到凝集素途径成分的缺陷来解释对无花果林结合血清型OFS的易感性增加。肺炎。老年人中炎性细胞因子水平的升高预示着炎症。然而，在我们研究的人群中，观察到的C1q的年龄和种族相关的变化以前没有报道过。这些发现与C1q在衰老相关病理中的研究相关，并与其作为虚弱和疾病的生物标记物的拟议作用有关。
Background There is increasing recognition of the significance of chronic, low-level inflammation in older adults, or "inflammaging." Innate immune responses and host-bacterial interactions are recognized as key factors in inflammaging. Inflammatory cytokine IL-6, and complement protein C1q have been identified as biomarkers for the development of frailty and aging-related diseases. Older adults are also susceptible to infections with serotypes ofStreptococcus pneumoniaethat bind ficolin-2, a component of the lectin complement pathway, and low ficolin-2 levels could possibly be involved in such susceptibility. Methods The aim of our study was to evaluate complement pathway components and biomarkers for inflammaging among older adults in order to investigate potential innate immune mechanisms that may account for susceptibility to infections in this population. We compared inflammatory markers, as well as components/activity of the classical and lectin complement pathways between healthy older and younger adults. We hypothesized that older adults would have higher levels of inflammatory markers and C1q, and lower levels of lectin pathway components. Older (>= 70 years old) and younger (19-54 years old) adults without significant smoking history or chronic medical conditions were eligible for participation. Inflammatory markers (IL-6, TNF-alpha, CRP), classical complement pathway activity (CH50) and protein levels (C1q, C3, C4), and lectin pathway (MBL levels/activity, CL-L1, MASP-1/2/3, MAp44, MAp19, and H/M/L-ficolin) were compared between groups. Results Older adults had significantly higher mean levels of IL-6 and TNF-alpha. There were no significant differences in lectin pathway components between older and younger adults. Unexpectedly, mean C1q was significantly higher in the younger group in both unadjusted and adjusted analyses. There was also a significant association between race and C1q levels, but this association did not completely account for the observed differences between age groups. Conclusions We did not observe deficiencies in lectin pathway components to account for increased susceptibility to ficolin-binding serotypes ofS. pneumoniae. Elevated levels of inflammatory cytokines in older adults are suggestive of inflammaging. However, the observed age and race-associated changes in C1q have not been previously reported in the populations included in our study. These findings are relevant to the investigation of C1q in aging-related pathology, and for its proposed role as a biomarker for frailty and disease.