Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn's Colitides

Olga Y Korolkova, Jeremy N Myers, Samuel T Pellom, Li Wang, Amosy E M'Koma, Olga Y Korolkova, Jeremy N Myers, Samuel T Pellom, Li Wang, Amosy E M'Koma

Abstract

Background: As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn's colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC.

Methods: We measured 38 cytokines, chemokines, and growth factors using magnetic-bead-based multiplex immunoassay in 25 UC patients, 28 CC patients, and 30 controls. Our results are compared with those from a review of current literature regarding advances in serum cytokine profiles and associated challenges preventing their use for diagnostic/prognostic purposes.

Results: Univariate analysis showed statistically significant increases of eotaxin, GRO, and TNF-α in UC patients compared to controls (Ctrl); interferon γ, interleukin (IL)-6, and IL-7 in CC group compared to Ctrl; and IL-8 in both UC and CC versus Ctrl. No cytokines were found to be different between UC and CC. A generalized linear model identified combinations of cytokines, allowing the identification of UC and CC patients, with area under the curve (AUC) = 0.936, as determined with receiver operating characteristic (ROC) analysis.

Conclusions: The current knowledge available about circulating cytokines in IBD is often contradictory. The development of an evidence-based tool using cytokines for diagnostic accuracy is still preliminary.

Keywords: Crohn’s disease; biomarkers; cytokines; inflammatory bowel disease; ulcerative colitis.

Figures

Figure 1
Figure 1
(A) Strength of marginal relationship between predictors and response using generalized Spearman chi-square for all patients and controls. (B) Fraction of zeros in each variable for ulcerative colitis and Crohn’s colitis patients. Abbreviations: Th, T-helper; IL, interleukin; IFN, interferon; sCD40L, soluble CD40 ligand; TNF, tumor necrosis factor; IL-1ra, IL-1 receptor antagonist; GRO, growth related oncogene; IP-10, interferon gamma-induced protein 10; MCP, monocyte chemoattractant protein; MDC, macrophage derived chemokine; MIP, macrophage inflammatory protein; EGF, epidermal growth factor; FGF-2, fibroblast growth factor 2; Flt-3L, hemopoietic growth factor Flt3 ligand; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; TGF, transforming growth factor.
Figure 2
Figure 2
Predicted probability for disease types, based on the generalized linear model. Abbreviations: UC, ulcerative colitis; CC, Crohn’s colitis.
Figure 3
Figure 3
(A) Publication years of the papers taken into this review (the number of papers published each year is indicated above the bars). (B) Distribution of sample sizes in the studies taken into this review (horizontal line, median; box, interquartile range; whiskers, minimum and maximum). (C) Medications that patients received at a time of blood sampling; indicated are number and percent of studies in which the corresponding treatments were used. (D) Serum storage conditions; indicated are numbers and percent of papers in which the corresponding storage is mentioned.

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