High Rate of Spontaneous Normalization of Celiac Serology in a Cohort of 446 Children With Type 1 Diabetes: A Prospective Study

Abstract

OBJECTIVEIn children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome. RESEARCH DESIGN AND METHODSAll children referred from 2002 to 2012 were screened for celiac disease (CD) at diabetes onset and at specific intervals. In the presence of a high anti-tTG titer or clinical symptoms, children were offered endoscopy, and asymptomatic patients with a low anti-tTG titer were invited to a second serological test after 6 months of eating a gluten-containing diet. RESULTSThe study included 446 children. Of these, 65 (14.5%) became positive for celiac serology: 38 (58%) had a persistently elevated anti-tTG titer and 27 (41%) fluctuating anti-tTG titer; 18 (28%) became negative. The prevalence of positive CD autoimmunity and overt CD was 14.3% (95% CI 11-17) and 8.5% (95% CI 5-10), 15-and 8-times higher than the general pediatric population, respectively. Asymptomatic children older than 9.1 years at T1DM onset had the lowest risk to develop CD. CONCLUSIONSSerum anti-tTG levels decreased spontaneously in 40% of children with T1DM and became negative in 20%, despite gluten consumption. This finding supports the hypothesis of a state of temporary positivity of celiac serology in children with diabetes. In absence of clinical symptoms or signs of CD, histological confirmation of the disease and the gluten-free diet should be postponed to avoid unnecessary procedures and reduce an additional psychological burden.

Comment on Castellaneta et al. High Rate of Spontaneous Normalization of Celiac Serology in a Cohort of 446 Children With Type 1 Diabetes: A Prospective Study. Diabetes Care 2015;38:760–766

“…However, the authors confirmed that all these subjects had a weak EmA reactivity. In the study by Castellaneta et al (1), the median time for tTG normalization was shorter than in our study, 1.3 years. We think it is unlikely that EmA can have a longer time for normalization than tTG, as the authors affirmed that they did not find any cases that were both EmA positive and tTG negative.…”

“…We read with interest the data reported by Castellaneta et al (1) about the spontaneous normalization of autoantibody markers for celiac disease (CD) in a wide population of children and adolescents with type 1 diabetes mellitus (T1DM). The authors hypothesized that this phenomenon could be related to a state of temporary positivity of celiac serology in children with T1DM.…”

High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes

“…Such transient autoantibodies may limit public acceptance of universal screening[15][38]. Others have also observed fluctuating tTGA[15] and transient tTGA antibodies in children with serial testing[39–41]. Continued long term follow-up will identify whether the autoimmunity in these subjects truly abates and tolerance develops, or if CDA will recur in time, possibly in response to additional stimulating events.…”

Coeliac disease and autoimmune disease—genetic overlap and screening

“…7,87 Spontaneous positive to negative sero conversion has been observed, which indicates that, at least in children, coeliac autoimmunity might be tran sient. [88][89][90] However, the same phenomenon occurs very rarely in adults. As coeliac disease remains undiagnosed in 60-80% of cases and 1-2% of individuals are at risk of coeliac disease, screening tools that do not depend on the patient's clinical presentation are needed.…”