Abstract
BackgroundBlood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers.MethodsWe investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann–Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsCXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-κB complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone.ConclusionsThe CD markers identified in this study further emphasize the significance of components related to NF-κB regulation in relation to CD. However, the relevance of CXCL11, TNFSF13B, TNFRSF9, and other NF-κB interacting proteins recognized by pathway analysis, needs to be further investigated in relation to diagnosis and monitoring of CD.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-230X-14-176) contains supplementary material, which is available to authorized users.
Highlights
Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD)
In cases with active CD (Table 1, Active CD), significantly increased levels were observed for CXCL11 protein (p = 0.003, Figure 1, Additional file 2) and TNFSF13B
TNFSF13B messenger RNA (mRNA) levels were significantly elevated in cases with confirmed CD and normalized histology (Table 1; Normalized CD), in comparison to cases without a CD diagnosis (p = 0.001, Figure 1, Additional file 2)
Summary
Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). A strong genetic component is Current CD diagnostics primarily include antibody detection, mainly of Immunoglobulin A (IgA) autoantibodies against TG2 (anti-TG2), and confirmation of the diagnosis by histopathologic assessment of small intestinal biopsies [13]. Group on Coeliac Disease Diagnosis suggested in 2012 that children and adolescents with clear symptoms and anti-TG2 levels over 10 times the upper limit of normal (ULN), with a remission of symptoms on a gluten-free diet (GFD), could be diagnosed with CD without histopathologic assessment of an intestinal biopsy [14]. We have previously developed a discriminant analysis model based on gene expression data in duodenal biopsies This model can discriminate between biopsies with and without histopathologic alterations indicative of CD, and indicate the level of histologic damage as well as mucosal recovery on a GFD [15]. The identification of blood-based markers which could reinforce the diagnostic value of anti-TG2, and perhaps indicate the level of histologic damage and mucosal recovery on GFD, would further simplify CD diagnostics
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
