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Erschienen in: Journal of Clinical Immunology 5/2013

01.07.2013 | Original Research

The Role of HLA DQ2 and DQ8 in Dissecting Celiac-Like Disease in Common Variable Immunodeficiency

verfasst von: Nils Venhoff, Florian Emmerich, Michaela Neagu, Ulrich Salzer, Corinna Koehn, Sibyll Driever, Wolfgang Kreisel, Marta Rizzi, Nora M. Effelsberg, Florian Kollert, Sigune Goldacker, Reinhard E. Voll, Klaus Warnatz, Jens Thiel

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2013

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Abstract

Objectives

Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and some of the patients present with celiac-like features. Diagnosing celiac disease (CD) in CVID however is challenging, as autoantibody detection and histopathology of the small intestine cannot reliably discriminate between classic CD and a celiac-like disease in these individuals. For the development of classic gluten-sensitive CD a certain HLA haplotype involving the loci DQA1* and DQB1* and encoding two different HLA DQ heterodimers is the prerequisite. We aimed to determine the frequency of these haplotypes in CVID patients with suspected CD. Furthermore, we report on autoimmune manifestations and the lymphocyte phenotype in these patients.

Methods

By retrospective analysis data on gastrointestinal symptoms, diet, concurrent autoimmune diseases, and routine laboratory values were collected. CVID patients were classified according to their B-cell phenotype. Expression of HLA-DQA1* and HLA-DQB1* alleles were determined by genetic analysis.

Results

Twenty out of 250 CVID patients presented with a clinical phenotype resembling celiac disease. Four (20 %) out of these CVID patients carried the CD-associated HLA DQ2.5 or DQ8 heterodimer, while HLA DQ2.5 was present in 100 % of a CD control cohort. Gluten-free diet (GFD) resulted in a clinical and histological response in two out of four patients with HLA high-risk alleles for CD. The response could not be assessed in the remaining two patients, as these patients did not adhere sufficiently long to GFD. The percentage of autoimmune manifestations other than CD was high (50 %) in CVID patients presenting with a CD-like enteropathy, and most of these patients had an expansion of B-cells with low expression of CD21 (CD21low B-cells).

Conclusions

In CVID patients with suspected celiac disease typing of the HLA loci DQA1 and DQB1 can help to identify those that have a genetic susceptibility for CD. In CVID patients with a celiac-like phenotype but negative for CD-associated HLA-DQ markers, an autoimmune enteropathy (AIE) as part of an extended autoimmune dysregulation needs to be considered. This has important implications for further diagnostics and therapy of these patients.
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Metadaten
Titel
The Role of HLA DQ2 and DQ8 in Dissecting Celiac-Like Disease in Common Variable Immunodeficiency
verfasst von
Nils Venhoff
Florian Emmerich
Michaela Neagu
Ulrich Salzer
Corinna Koehn
Sibyll Driever
Wolfgang Kreisel
Marta Rizzi
Nora M. Effelsberg
Florian Kollert
Sigune Goldacker
Reinhard E. Voll
Klaus Warnatz
Jens Thiel
Publikationsdatum
01.07.2013
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 5/2013
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-013-9892-3

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