Host Immune Markers Distinguish Clostridioides difficile Infection From Asymptomatic Carriage and Non-C. difficile Diarrhea
Host Immune Markers Distinguish Clostridioides difficile Infection From Asymptomatic Carriage and Non-C. difficile Diarrhea
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DOI：
10.1093/cid/ciz330
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发表时间：
2020-03-15
影响因子：
11.8
通讯作者：
Pollock, Nira R.
中科院分区：
文献类型：
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作者：
Kelly, Ciaran P.;Chen, Xinhua;Pollock, Nira R.
背景最近的数据表明粪便中艰难梭菌毒素浓度不能区分C.艰难梭菌感染（CDI）和无症状携带。因此，我们缺乏一种方法来区分有症状的CDI患者与其他原因引起腹泻的定植患者。为了解决这一问题，我们评估了先天性和适应性免疫标记物与CDI（根据美国指南诊断），无症状携带，或非CDI diarrheum.Methods CDI-NAAT患者有临床意义的腹泻和阳性核酸扩增试验（NAAT），并接受CDI治疗的成人住院患者。NAAT携带者粪便NAAT阳性，但无腹泻。NAAT阴性患者（伴和不伴腹泻）也入组。在血清中测量一组细胞因子和抗毒素A和B免疫球蛋白（Ig）;在粪便中测量钙卫蛋白和抗毒素B IG A/G。NAAT阳性粪便样本通过超灵敏毒素检测进行检测结果白细胞介素（IL）-4、IL-6、IL-8、IL-10、IL-15、粒细胞集落刺激因子（GCSF）、MCP-1、肿瘤坏死因子α（TNF α）的中位数CDI患者血液中的TNF-α、IgG抗毒素A和粪便中的伊加/G抗毒素B显著高于所有其他组（P <0.05）。浓度分布IL-6，GCSF，TNF-α，IgG抗毒素A在血液中，以及伊加和IgG抗毒素B在粪便中，分离CDI患者从所有其他groups.Conclusions特异性标志物的先天性和适应性免疫CDI从所有其他组区分，这表明潜在的临床效用，确定NAAT和毒素阳性腹泻患者真正有CDI。
Background Recent data indicate that Clostridioides difficile toxin concentrations in stool do not differentiate between C. difficile infection (CDI) and asymptomatic carriage. Thus, we lack a method to distinguish a symptomatic patient with CDI from a colonized patient with diarrhea from another cause. To address this, we evaluated markers of innate and adaptive immunity in adult inpatients with CDI (diagnosed per US guidelines), asymptomatic carriage, or non-CDI diarrhea.Methods CDI-NAAT patients had clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment. Carrier-NAAT patients had positive stool NAAT but no diarrhea. NAAT-negative patients (with and without diarrhea) were also enrolled. A panel of cytokines and anti-toxin A and B immunoglobulin (Ig) were measured in serum; calprotectin and anti-toxin B Ig A/G were measured in stool. NAAT-positive stool samples were tested by an ultrasensitive toxin assay (clinical cutoff, 20 pg/mL).Results Median values for interleukin (IL)-4, IL-6, IL-8, IL-10, IL-15, granulocyte colony-stimulating factor (GCSF), MCP-1, tumor necrosis factor alpha (TNF-alpha), and IgG anti-toxin A in blood and IgA/G anti-toxin B in stool were significantly higher in CDI patients compared with all other groups (P < .05). Concentration distributions for IL-6, GCSF, TNF-alpha, and IgG anti-toxin A in blood, as well as IgA and IgG anti-toxin B in stool, separated CDI patients from all other groups.Conclusions Specific markers of innate and adaptive immunity distinguish CDI from all other groups, suggesting potential clinical utility for identifying which NAAT- and toxin-positive patients with diarrhea truly have CDI.