Presymptomatic Diagnosis of Celiac Disease in Predisposed Children: The Role of Gene Expression Profile
Objective:
The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at-risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at-risk infants long time before any symptom or production of antibodies.Methods:
We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at-risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4–19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten-free diet. At similar age points, controls were also evaluated. Results:
Three genes (KIAA, TAGAP [T-cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G-protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of patients. Conclusions:
The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.
The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at-risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at-risk infants long time before any symptom or production of antibodies.
We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at-risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4–19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten-free diet. At similar age points, controls were also evaluated.
Three genes (KIAA, TAGAP [T-cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G-protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of patients.
The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.
Keywords: celiac disease; celiac disease first-degree relatives; gene expression; presymptomatic diagnosis; risk factors
Document Type: Research Article
Affiliations: 1: Department of Translational Medical Science, University of Naples Federico II, Naples, Italy, European Laboratory for Food-Induced Disease (ELFID), University of Naples Federico II, Naples, Italy 2: Department of Translational Medical Science, University of Naples Federico II, Naples, Italy 3: Pediatric Unit, University Hospital of Salerno, Cava de’ Tirreni 4: European Laboratory for Food-Induced Disease (ELFID), University of Naples Federico II, Naples, Italy, Institute of Protein Biochemistry-CNR, Naples, Italy.
Publication date: 01 September 2017
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