Predominantly Antibody Deficiency and the Association with Celiac Disease in Sweden: A Nationwide Case-Control Study.

BACKGROUND: Predominantly antibody deficiency (PAD) is associated with non-infectious inflammatory gastrointestinal (GI) disease. Population estimates of celiac disease (CeD) risk in those with PAD are limited.

OBJECTIVE: Estimate population risk of PAD in individuals with CeD.

METHODS: We conducted a nationwide case-control study of Swedish individuals who received a diagnosis of CeD between 1997 and 2017 (n=34,980), matched to population comparators by age, sex, calendar year, and county. CeD was confirmed through the Epidemiology Strengthened by histopathology Reports in Sweden (ESPRESSO) study, which provided information on biopsy specimens from each of Sweden's pathology departments. PAD was identified using International Classification of Diseases (ICD) 10th Revision coding and categorized according to the International Union of Immunologic Societies (IUIS). Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

RESULTS: PAD was more prevalent in CeD as compared to population controls (n=105 (0.3%) vs n=57 (0.033%), respectively). This translated to an aOR of 8.23 (95%CI 5.95-11.48). The association was strongest with common variable immunodeficiency (CVID) (aOR 17.25; 95%CI 6.86-52.40), and slightly lower in other PAD (aOR 8.39; 95%CI 5.79-12.32). The risk of CeD remained increased ≥ 5 years after diagnosis of PAD (aOR 4.79; 95%CI 2.89-7.97, p-heterogeneity <0.001).

CONCLUSION: PAD was associated with an increased risk of CeD. A particularly strong association was seen in those with CVID, although should be interpreted cautiously given the limited understanding of the mechanisms of histopathologic changes in these patients.