Anti-microbial antibodies in celiac disease: trick or treat?

Abstract

Aim: To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti-OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients.

Methods: 190 consecutive CD patients [M/F: 71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD).

Results: 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, anti-microbial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+: 3.13; 95% CI: 2.08-4.73) was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis (P = 0.019).

Conclusion: The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.

Figure 1

Anti-microbial antibody levels in 190 patients with celiac disease and in control groups. Individual values are shown by black spots. Mean values with standard error bars are indicated in gray. Cut-off values for positivity are pointed out by dotted line and 50, 100, 60, 90 and 25 U/mL for gASCA IgG, AMCA IgG, ALCA IgG, ACCA IgA and OMP IgA, respectively.

Figure 2

Clinical presentation of celiac disease according to serological response.

Figure 3

Individual anti-glycan and anti-OMP antibody titers at the time of the diagnosis and their variations after successful adherence of to the gluten-free diet (GFD). Mean follow up period of 49 [10-159] mo (n = 30). Dotted lines show cut-off values for positivity.