Serological Investigation of Persistent Villous Atrophy in Celiac Disease

INTRODUCTION: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). METHODS: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. RESULTS: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group (P 5 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. DISCUSSION: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.