Title: Assessment of the possibility of using measurements of inflammatory mediators in the diagnosis of Leśniowski-Crohn disease


Introduction Crohn's disease (CD), one of the inflammatory bowel diseases (IBD), is a transmural, usually granulomatous inflammation that can affect any part of the gastrointestinal tract. The main mechanism of intestinal inflammation in CD is the imbalance between Th1 and Th17 effector lymphocytes acting through the secretion of IFN-γ, TNF-α, pro-inflammatory interleukins such as IL-6, IL-12, IL-17, IL-22 and other mediators, and regulatory T cells (Treg) secreting IL-10, IL-35 and TGF-β. Although the role of many cytokines in the pathogenesis and clinical course of CD is widely researched and well explained, they are not used for diagnostic purposes. Many articles have been published on the cytokine networks and serum level profiles in IBD, but data on their diagnostic characteristics are scarce. The aim of the study was to compare the serum concentrations of inflammatory markers / mediators, including CRP, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-19 and IL-23, and the results of their multiplication between patients with CD, its active and inactive form and a control group and the assessment of their diagnostic characteristics in the diagnosis / exclusion of CD and its active phase. Methods The study group consisted of 49 patients with CD assigned to the active (33 patients) and inactive (16 patients) disease subgroups based on CDAI, and 31 healthy controls. Se ; rum CRP was measured using immunonephelometry and cytokines – using ELISA. Serum mediator / marker levels and their multiplication results, including [IL-6]×[CRP], [IL-17A]×[CRP], [IL- 23]×[CRP], [IL-6]×[IL-17A], [IL-6]×[IL-23], [IL-17A]×[IL-23], [IL-6]×[IL-10], [IL-6]×[1L- 19], [IL-6]×[IFN-γ], [CRP]×[IL-10], [CRP]×[1L-19], [CRP]×[IFN-γ], [IL-10]×[IL-19], [IL- 10]×[IFN-γ] and [IL-19]×[IFN-γ] were compared between the study groups. Their diagnostic characteristics for the diagnosis / exclusion of CD and its active form were assessed, including sensitivity, specificity, predictive values of the result; likelihood ratios and area under the ROC curve (AUC). Results Serum levels of CRP, IFN-γ, IL-6, IL-12, IL-17A, IL-19 and IL-23, and their multiplication results were significantly higher in CD patients than in controls (p <0.0001–0.007). The levels of CRP, IFN-γ, IL-6, IL-12 and IL-19, and their multiplication results were significantly higher in patients with active than inactive disease and controls (p <0.0001–0.026). Serum IFN-γ and IL-12 levels correlated with CDAI values. In the diagnosis / exclusion of CD, IL-23 performed best with diagnostic sensitivity 0.96, specificity 0.97, PPV 0.98, NPV 0.94, LR+ 29.9, LR- 0.004 and AUC 0.994. Similarly performed multiplications of serum IL-23 and CRP, IL-6 and IL-17A. The [CRP]×[IL-19] and [IL-6]×[IFN-γ] results had a ; specificity 0.96, PPV 0.97 and LR+ 15.0 and 15.5, respectively. Serum IL-19 and the [IL-6]×[IL-12] and IFN-γ]×[IL-12] results had a sensitivity 0.9-0.96, NPV 0.75-0,86 and LR- 0.09-0.18 in the exclusion of CD. The AUC for these markers was 0.776- 0.807. In the diagnosis of active CD, serum CRP had a specificity and PPV 1.0 and AUC 0.84, while the [CRP]×[IL-10] and [CRP]×[IL-19] results – a specificity 0.98, PPV 0.96, LR+ 33.4 and 30.5, and AUC 0.896 and 0.895, respectively. Serum IFN-γ and the [CRP]×[IFN-γ], [CRP]×[IL-12] and [IFN-γ]×[IL-19] results had a sensitivity 0.77-0.94, NPV 0.86-0.93, LR- 0.11-0.24 and AUC 0.781–0.904 in excluding active CD. IL-6, IL-10, IL-12 and IL-17A, as single markers, turned out not to be useful in the diagnosis / exclusion of CD or its active form, although the listed combined markers (multiplication results) containing them had promising diagnostic characteristics. Conclusions Serum CRP, IFN-γ, IL-6, IL-12, IL-17A, IL-19 and IL-23 levels were significantly higher in patients with CD than in the control group, and the concentrations of CRP, IFN-γ, 6, IL-10, IL- 12 and IL-19 - significantly higher in patients with active than inactive form of the disease and in the control group. Serum IL-23, CRP, IFN-γ and IL-19 levels and some of the results of their multiplication showed promising diagnostic characteristics in the diagnosis / e ; xclusion of CD and its active form, which requires further studies. If their favorable diagnostic features are confirmed, it will be necessary to standardize and automate the IFN-γ, IL-19 and IL-23 assays before their implementation in clinical practice.

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2 - studia doktoranckie

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Rada Dyscypliny Nauki medyczne


Malczewska-Malec, Małgorzata

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pol; eng

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Jun 5, 2024

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ZB-140221 Jun 5, 2024


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