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Gastrointestinal (GI) disorders are present in 5–50 % of patients with primary immunodeficiencies. These manifestations mimic classic forms of disease (in the absence of immunodeficiency) such as celiac disease, food allergy, or inflammatory bowel disease, but they are often unresponsive to conventional therapies. Because GI disease may be the first presentation of an underlying immunodeficiency, it is crucial to consider immunodeficiency in any child with recurrent or chronic severe diarrhea, malabsorption, and failure to thrive resistant to conventional treatments. At the same time, routine evaluation of GI tract is useful for children with immunodeficiency, given the high incidence of GI disorders in these patients and considering that early evaluation and diagnosis can prevent potentially irreversible tissue damage. Primary immunodeficiencies are relatively common but likely underdiagnosed. A clinical history of recurrent, opportunistic, or unusual infections; histological features that do not fit the usual pattern of disease; and a poor response to conventional therapy should prompt the pediatrician to pursue further immunologic evaluation in collaboration with the immunologist.

AIM: Celiac disease (CD) is a multifactorial autoimmune disease induced by ingestion of gluten in genetically predisposed individuals. Despite technological progress, the diagnosis of CD is still based on duodenal biopsy as it was 50 years ago. In this study we analysed the expression of CD-associated genes in small bowel biopsies of patients and controls in order to explore the multivariate pathway of the expression profile of CD patients. Then, using multivariant discriminant analysis, we evaluated whether the expression profiles of these genes in peripheral blood monocytes (PBMs) differed between patients and controls. PARTICIPANTS: Thirty-seven patients with active and 11 with treated CD, 40 healthy controls and 9 disease controls (Crohn's disease patients) were enrolled. RESULTS: Several genes were differentially expressed in CD patients versus controls, but the analysis of each single gene did not provided a comprehensive picture. A multivariate discriminant analysis showed that the expression of 5 genes in intestinal mucosa accounted for 93% of the difference between CD patients and controls. We then applied the same approach to PBMs, on a training set of 20 samples. The discriminant equation obtained was validated on a testing cohort of 10 additional cases and controls, and we obtained a correct classification of all CD cases and of 91% of the control samples. We applied this equation to treated CD patients and to disease controls and obtained a discrimination of 100%. CONCLUSIONS: The combined expression of 4 genes allows one to discriminate between CD patients and controls, and between CD patients on a gluten-free diet and disease controls. Our results contribute to the understanding of the complex interactions among CD-associated genes, and they may represent a starting point for the development of a molecular diagnosis of celiac disease.