Abstract
Risk of celiac disease (CD) is increased in relatives of CD patients due to genetic and possible environmental factors. We recently reported increased seropositivity to anti-Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (anti-I2) and Bacteroides caccae TonB-linked outer membrane protein (anti-OmpW) antibodies in CD. We hypothesized these markers also to be overrepresented in relatives. Seropositivity and levels of ASCA, anti-I2 and anti-OmpW were compared between 463 first-degree relatives, 58 untreated and 55 treated CD patients, and 80 controls. CD-associated human leukocyte antigen (HLA)-haplotypes and transglutaminase (tTGab) and endomysium (EmA) antibodies were determined. One or more of the microbial antibodies was present in 75% of relatives, 97% of untreated and 87% of treated CD patients and 44% of the controls. The relatives had higher median ASCA IgA (9.13 vs. 4.50 U/mL, p < 0.001), ASCA IgG (8.91 vs. 5.75 U/mL, p < 0.001) and anti-I2 (absorbance 0.74 vs. 0.32, p < 0.001) levels than controls. There was a weak, positive correlation between tTGab and ASCA (r = 0.31, p < 0.001). Seropositivity was not significantly associated with HLA. To conclude, seropositivity to microbial markers was more common and ASCA and anti-I2 levels higher in relatives of CD patients than controls. These findings were not associated with HLA, suggesting the role of other genetic and environmental factors.
Highlights
Celiac disease (CD) is an immune-mediated condition characterized by gluten-induced small-bowel enteropathy
The gender distribution was fairly equal among the relatives, whereas a majority of CD patients were women, and there were more men in the non-CD control group (Table 1)
The main finding of the present study was increased seroreactivity to microbial markers in the relatives of CD patients compared with controls even after the exclusion of CD autoantibody-positive individuals
Summary
Celiac disease (CD) is an immune-mediated condition characterized by gluten-induced small-bowel enteropathy. Almost all patients carry human leukocyte antigen (HLA) alleles encoding. DQ2 or DQ8 heterodimers [1] These alleles are present in up to 35% of the general population and do not fully explain the genetic risk [2]. Due to shared genetic predisposition, the relatives of patients. Nutrients 2020, 12, 1073 have an increased susceptibility to CD, the average prevalence among first-degree relatives being approximately 8% [5] compared with 1%–2% in the general population [6,7]. The prevalence may vary between adjacent countries with similar genetic backgrounds and gluten consumption [10], and retrospective measurements of stored samples indicate a rise in the true incidence [6,11,12]
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