International Journal of Medical Sciences And Clinical Research
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VOLUME
Vol.05 Issue05 2025
PAGE NO.
1-5
Progression of celiac disease in children with antibodies
against tissue transglutaminase and normal duodenal
architecture
Marcio Fleites
Department of Pediatric Immunology, University of Madrid, Spain
Rico Linan
Department of Pediatrics, University Hospital, Valencia, Spain
Received:
03 March 2025;
Accepted:
02 April 2025;
Published:
01 May 2025
Abstract:
Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten ingestion in genetically
predisposed individuals. While the classic presentation involves intestinal damage, a subset of children presents
with positive celiac-specific antibodies, particularly against tissue transglutaminase (tTG), but have normal or
near-normal duodenal villous architecture upon biopsy. This condition is often referred to as potential celiac
disease (PCD). Understanding the natural history and factors influencing the progression from PCD to overt CD
(characterized by mucosal atrophy) is crucial for clinical management. This article synthesizes findings from recent
studies to explore the progression of CD in children with positive tTG antibodies and initially normal duodenal
architecture. It examines factors associated with progression, potential biomarkers, and current diagnostic and
management approaches for this specific pediatric population.
Keywords:
Celiac Disease, Tissue Transglutaminase Antibodies, Pediatric Gastroenterology, Duodenal
Architecture, Antidiv Testing, Pediatric Immunology, Gluten Sensitivity, Disease Progression, Gluten-Free Diet,
Children’s Health, Gastrointestinal Disorders, Intestinal Biopsy, Immune Response, Chronic Autoimmune Diseases,
Serology Markers, Early Diagnosis.
Introduction:
Celiac disease is a common condition
affecting both children and adults, characterized by an
immune response to gluten that leads to inflammation
and damage in the small intestine (Abadie et al., 2024)
[7]. The diagnosis typically relies on a combination of
positive celiac-specific antibodies, such as anti-tissue
transglutaminase (tTG) antibodies, and characteristic
histological changes in duodenal biopsies, including
villous atrophy (Marsh stage 3) (Auricchio et al., 2019)
[1]. However, a significant number of children are
identified with positive celiac serology but show no or
minimal damage to the intestinal mucosa (Marsh stage
0 or 1) upon initial biopsy (Auricchio et al., 2019) [1].
This clinical scenario is often termed potential celiac
disease (PCD) (Nemteanu et al., 2023) [6].
The trajectory of PCD in children is variable; some
children may remain stable with positive antibodies but
no mucosal damage, while others will progress to
develop the characteristic villous atrophy of overt CD
over time (Auricchio et al., 2019) [1]. The decision to
implement a gluten-free diet (GFD) in children with PCD
is a subject of ongoing debate and varies between
clinical guidelines (Nemteanu et al., 2023) [6].
Predicting which children with PCD will progress to
overt CD is a key challenge in pediatric
gastroenterology (Piccialli et al., 2021) [14]. This article
aims to review recent research on the progression of
CD in children presenting with positive tTG antibodies
and normal duodenal architecture, highlighting insights
into predictive factors, diagnostic strategies, and
potential future directions.
METHODS
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
This article is based on a narrative review and synthesis
of the provided scientific literature focusing on the
progression of celiac disease in children, particularly
those with positive serology and normal duodenal
architecture. The included references consist of original
research articles, review articles, and conference
abstracts published between 2019 and 2024.
The approach involved reviewing each provided
reference to identify key findings, methodologies, and
conclusions related to:
1.
The definition and characteristics of potential
celiac disease in children.
2.
The rate and factors associated with the
progression from potential to overt celiac disease.
3.
The role of celiac-specific antibodies (especially
tTG) in predicting progression.
4.
The significance of duodenal histology in the
context of positive serology.
5.
The exploration of potential biomarkers for
predicting mucosal lesion progression.
6.
Diagnostic approaches and management
strategies for children with positive serology and
normal mucosa.
Information from these sources was synthesized to
provide an overview of the current understanding of CD
progression in this specific pediatric population. The
findings and discussion presented are directly derived
from the content of the provided references, with
numerical citations used throughout the text to
indicate the source of the information.
RESULTS
Studies have demonstrated that a substantial
proportion of children with positive tTG antibodies and
normal duodenal architecture at initial biopsy do
progress to overt celiac disease over time (Auricchio et
al., 2019) [1]. A retrospective cohort study observed
the progression from PCD to CD in pediatric patients
(Sakhuja & Holtz, 2021) [12]. The rate of progression
can vary, and identifying factors that predict this
progression is an active area of research.
Higher titers of tTG antibodies at diagnosis have been
consistently associated with an increased risk of
progression to mucosal atrophy (Auricchio et al., 2019)
[1]. The dynamics of autoantibodies, including tTG, in
pediatric CD and their relationship with age and disease
progression are being investigated (Trovato et al.,
2023) [8, 25].
While initial duodenal architecture is normal, subtle
changes or the presence of specific cellular markers in
the intestinal epithelium might precede overt villous
atrophy. Research is exploring intestinal cellular
biomarkers that could indicate mucosal lesion
progression in pediatric CD (Vitale et al., 2021) [9, 26].
New intraepithelial γδ T
-lymphocyte markers are being
investigated for their potential in classifying CD in
duodenal biopsies (Popp et al., 2021) [24]. Molecular
biomarkers are also being explored for their role in the
past, present, and future diagnosis and understanding
of CD (Ramírez-Sánchez et al., 2020) [17, 31].
Diagnostic approaches for children with positive
serology and normal mucosa are evolving. While
duodenal biopsy remains a key diagnostic tool,
particularly in cases with high-titer serology, there are
ongoing discussions and variations in biopsy policies
between regions like Europe and North America
(Badizadegan et al., 2020) [19]. Novel diagnostic tests,
such as intestinal and blood lymphograms, are being
explored (Roy et al., 2023) [4, 28]. Dual sugar
absorption tests, using monosaccharides like rhamnose
and mannitol, are also being evaluated for their utility
in treatment-naïve children with CD (Holtz et al., 2022)
[3, 27].
The management of children with PCD, specifically
regarding the initiation of a GFD, remains a clinical
challenge (Trovato et al., 2019) [15, 21]. The question
of whether and when to implement a GFD in PCD is
actively debated (Nemteanu et al., 2023) [6].
Research is also exploring the genetic and
environmental factors that might influence the
development and progression of CD autoimmunity.
Studies are investigating associations between CD
autoimmunity and factors like maternal tuberculosis
and pediatric Helicobacter pylori infections in
genetically predisposed birth cohorts (Gudeta et al.,
2022) [10, 11]. The complex interplay of genes, gluten,
and the immunopathogenesis of CD is a subject of
ongoing research (Abadie et al., 2024) [7].
Predictive modeling, including the use of machine
learning, is being explored to predict the outcome of
potential celiac disease (Piccialli et al., 2021) [14].
Recent progress and recommendations on CD from
working groups are contributing to a better
understanding and management of the disease (Scherf
et al., 2020) [16, 22]. The broader context of becoming
and being celiac, with special considerations for
childhood and adolescence, is also being addressed in
recent reviews (Chang et al., 2022) [5, 29].
DISCUSSION
The progression of celiac disease in children with
positive tTG antibodies and normal duodenal
architecture represents a complex clinical scenario that
requires careful consideration. The findings from the
reviewed literature underscore that this group is at a
significant risk of developing overt mucosal damage
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
over time (Auricchio et al., 2019) [1]. The variability in
progression highlights the need for better predictive
markers and individualized management strategies.
High tTG antidiv titers appear to be a consistent
indicator of increased risk of progression (Auricchio et
al., 2019) [1]. However, relying solely on antidiv levels
may not be sufficient for accurate prediction,
emphasizing the need for additional markers. The
investigation into intestinal cellular biomarkers (Vitale
et al., 2021) [9, 26] and new intraepithelial lymphocyte
markers (Popp et al., 2021) [24] holds promise for
identifying subtle changes in the duodenal mucosa that
precede overt atrophy. These efforts align with the
broader search for molecular biomarkers in CD
(Ramírez-Sánchez et al., 2020) [17, 31].
The role of duodenal biopsy in children with positive
serology but normal mucosa remains a point of
discussion and clinical variation (Badizadegan et al.,
2020) [19]. While some guidelines may advocate for
biopsy in certain cases, the invasive nature of the
procedure necessitates the exploration of less invasive
or more accurate predictive tools. Novel diagnostic
tests, such as lymphograms (Roy et al., 2023) [4, 28])
and refined absorption tests (Holtz et al., 2022) [3, 27],
could potentially contribute to a more nuanced
diagnostic approach in the future.
Fig. Celiac Disease: Diagnostic Standards and Dilemmas
The decision to initiate a GFD in children with PCD is
challenging, balancing the potential benefits of
preventing mucosal damage against the burden and
social implications of a strict diet (Nemteanu et al.,
2023) [6]; (Trovato et al., 2019) [15, 21]. More research
is needed to determine the optimal management
strategy for this group, potentially guided by improved
predictive tools.
Understanding the interplay of genetic predisposition,
environmental factors (Gudeta et al., 2022) [10, 11],
and the immune response to gluten (Abadie et al.,
2024) [7] is crucial for comprehending the mechanisms
driving progression. Advances in precision medicine
and machine learning offer exciting possibilities for
integrating various data points to predict individual
outcomes in PCD (Piccialli et al., 2021) [14].
CONCLUSION
In conclusion, the progression of celiac disease in
children with positive tTG antibodies and normal
duodenal architecture is a dynamic process. While
serology provides an initial indication, predicting
progression requires a deeper understanding of
underlying
biological
mechanisms
and
the
development of more precise biomarkers. Continued
research into intestinal cellular changes, novel
diagnostic methods, and predictive modeling is
essential to refine diagnostic strategies and guide
clinical management for this specific pediatric
population, ultimately aiming to optimize outcomes
and potentially prevent the development of overt
celiac disease.
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