Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

Nutrients

Floriana Giorgio¹  Mariabeatrice Principi¹  Giuseppe Losurdo¹  Domenico Piscitelli²  Andrea Iannone¹  Michele Barone¹  Annacinzia Amoruso¹  Enzo Ierardi¹ 

[1] Section of Gastroenterology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; E-Mails:;Section of Pathology, University Hospital Policlinico, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; E-Mail:

关键词: seronegative celiac disease;    tissue-transglutaminase mRNA;    common variable immunodeficiency;    selective IgA deficiency;    selective IgM deficiency;    gluten-free diet;   

DOI  :  10.3390/nu7095350

来源: mdpi

【 摘 要 】

In 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.