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
Diabetes Care 2015;38:e188 | DOI: 10.2337/dc15-1208
We read with interest the data reported
by Castellaneta et al. (1) about the spon-
taneous 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 phenome-
non could be related to a state of tempo-
rary positivity of celiac serology in children
with T1DM. They concluded that a gluten-
free diet should be delayed in the
absence of clinical signs of CD and that
these subjects should be carefully fol-
lowed up with serological and histolog-
ical tests for a con fi rmation of the
diagnosis.
We partially agree with the authors’
conclusions, and we would like to share
our experience about the association of
T1DM and CD, highlighting some differ-
ences previously reported. We investi-
gated the prevalence of CD in a cohort
of 331 newly diagnosed subjects with
T1DM (2) over an 18-year follow-up
based on anti-endomysial antibody
(EmA) screening. We found that 7 of
29 subjects (24%) showed positivity for
EmA detected at T1DM onset or during
routine follow-up. The laboratory find-
ings were confirmed by subsequent
evaluations. Three of them underwent
biopsy before normalization and a nor-
mal mucosa was found. In all of these
subjects, EmA spontaneously serocon-
verted and became negative during a
follow-up of 2–8 years. Castellaneta
et al. cited another study (3) on EmA
screening in subjects with T1DM that
reported that 30% of EmA-positive chil-
dren were already found negative at the
second assay. 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. A different interpreta-
tion may be that this is not related to
gluten consumption (all the children
who normalized CD-related antibodies
follow a gluten-containing diet), but it is
simply an epiphenomenon of the autoim-
mune activation shown in subjects with
T1DM. In fact, Waisbourd-Zinman et al.
(4) also reported a study on spontaneous
normalization of tTG in subjects with
T1DM; the data showed that up to one-
third of subjects with positive tTG levels
seroconverted within 1 year of follow-up.
Surprisingly, they found that sometimes
EmA did not normalize accordingly to tTG:
in fact, 3 of 10 subjects with EmA- and
tTG-positive levels not on a gluten-free
diet showed only tTG normalization dur-
ing the follow-up period. Therefore, the
association between CD and T1DM still
remains a fascinating field of study with
many aspects still to be clearly under-
stood. In subjects with a predisposition
for autoimmune diseases, autoanti-
bodies can appear even at a low titer,
and their meaning needs to be carefully
interpreted.
Duality of Interest. No potential conflicts of
interest relevant to this article were reported.
References
1. Castellaneta S, Piccinno E, Oliva M, et al. High
rate of spontaneous normalization of celiac se-
rology in a cohort of 446 children with type 1
diabetes: a prospective study. Diabetes Care
2015;38:760–766
2. Salardi S, Volta U, Zucchini S, et al. Preva-
lence of celiac disease in children with type 1
diabetes mellitus increased in the mid-1990 s:
an 18-year longitudinal study based on anti-
endomysial antibodies. J Pediatr Gastroenterol
Nutr 2008;46:612–614
3. Barera G, Bonfanti R, Viscardi M, et al. Oc-
currence of celiac disease after onset of type 1
diabetes: a 6-year prospective longitudinal
study. Pediatrics 2002;109:833–838
4. Waisbourd-Zinman O, Hojsak I, Rosenbach Y,
et al. Spontaneous normalization of anti-tissue
transglutaminase antibody levels is common in
children with type 1 diabetes mellitus. Dig Dis
Sci 2012;57:1314–1320
Department of Pediatrics, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
Corresponding author: Giulio Maltoni, giulio.maltoni2@unibo.it.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,
and the work is not altered.
Giulio Maltoni, Silvana Salardi, and
Stefano Zucchini
e188 Diabetes Care Volume 38, November 2015
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