Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?
AbstractIn the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association. View Full-Text
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Giorgio, F.; Principi, M.; Losurdo, G.; Piscitelli, D.; Iannone, A.; Barone, M.; Amoruso, A.; Ierardi, E.; Di Leo, A. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg? Nutrients 2015, 7, 7486-7504.
Giorgio F, Principi M, Losurdo G, Piscitelli D, Iannone A, Barone M, Amoruso A, Ierardi E, Di Leo A. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg? Nutrients. 2015; 7(9):7486-7504.Chicago/Turabian Style
Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Iannone, Andrea; Barone, Michele; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo. 2015. "Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?" Nutrients 7, no. 9: 7486-7504.