Background Gastrointestinal manifestations are frequent in patients with common variable immunodeficiency (CVID), and present with celiac-like features in a subgroup of these patients. On the other hand diagnosing bona fide/authentic celiac disease (CD) in CVID is challenging, as serology and small intestine histopathology cannot reliably discriminate between true CD and a celiac-like disease phenotype in these individuals. In CD a special HLA haplotype involving the loci DQA1* and DQB1* and encoding two different HLA DQ heterodimers is the prerequisite for disease development.
Objectives We aim 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, concurrent autoimmune diseases, and routine laboratory values were collected. CVID patients were classified by phenotyping of their peripheral B-lymphocytes. HLA-DQA1* and HLA-DQB1* genes were analyzed to determine the frequency of CD associated heterodimers.
Results 20 out of 250 CVID patients presented with a clinical phenotype resembling celiac disease. 5 (25%) 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 2 out of 5 patients with HLA high-risk alleles for CD. The response could not be assessed in the remaining 3 patients, as these patients did not adhere sufficiently long to GFD. The percentage of autoimmune manifestations other then 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 negativity for the HLA-DQ markers predisposing to CD, an alternative pathogenesis of gastrointestinal manifestations should be favoured. This has important implications for further diagnostics and therapy of these patients.
Disclosure of Interest None Declared