Evaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease

doi:10.1016/S0022-3476(84)80074-8

The Journal of Pediatrics

Volume 105, Issue 6, December 1984, Pages 901-905

https://doi.org/10.1016/S0022-3476(84)80074-8 Get rights and content

Serum IgA class reticulin antibody (RA) was found in 28 (97%) of 29 children with flat small bowel mucosa, and in low titer in four (2%) of 245 with normal or near normal mucosa on small intestinal biopsy. Thus the sensitivity of the IgA-RA fluorescent antibody test for screening of celiac disease was 97% and the specificity 98%. IgA-RA was superior to IgG-RA for the detection of celiac disease. During follow-up of patients receiving a gluten-free diet, the IgA-RA rapidly decreased and in most cases disappeared within a year, suggesting that the test may be useful for clinical follow-up of celiac disease as well.

References (26)

LebenthalE et al.
Childhood celiac disease: A reappraisal
J Pediatr
(1981)
Bürgin-WolffA et al.
A reliable screening test for childhood celiac disease: Fluorescent immunosorbent test for gliadin antibodies
J Pediatr
(1983)
CacciariE et al.
Short stature and celiac disease: A relationship to consider even in patients with no gastrointestinal tract symptoms
J Pediatr
(1983)
SeahPP et al.
Anti-reticulin antibodies in childhood coeliac disease
Lancet
(1971)
UnsworthDJ et al.
Gliadin and reticulin antibodies in childhood coeliac disease
Lancet
(1983)
VoltaU et al.
Gliadin antibodies in coeliac disease
Lancet
(1983)
SavilahtiE et al.
IgA antigliadin antibodies: A marker of mucosal damage in childhood coeliac disease
Lancet
(1983)
AlpMH et al.
Autoantibodies to reticulin in patients with idiopathic steatorrhoea, coeliac disease and Crohn's disease and their relation to immunoglobulins and dietary antibodies
Lancet
(1971)
LittlewoodJM et al.
Childhood coeliac disease is disappearing
Lancet
(1980)
DossetorJFB et al.
Childhood coeliac disease is disappearing
Lancet
(1981)

SwinsonCM et al.

Is coeliac disease underdiagnosed?

Br Med J

(1980)

StenhammarL

Transient gastrointestinal disorders during infancy and early childhood: A follow-up study with special reference to coeliac disease

Acta Paediatr Scand

(1981)

Von EssenR et al.

Reticulin antibody in children with malabsorption

Lancet

(1972)

Cited by (111)

Clinical usefulness of serum antibodies as biomarkers of gastrointestinal and liver diseases
2017, Digestive and Liver Disease
Citation Excerpt :
They were detected by standard indirect immunofluorescence on cryostat section of rodent tissues, stomach, liver and kidney. Although some authors reported remarkably good levels of sensitivity and specificity [33], in everyday clinical practice the results were more disappointing and they never became a test used world-wide. The era of coeliac serology kicked off in the early 1980s with the discovery of ELISA anti-gliadin antibodies (AGA) and immunofluorescent anti-endomysial antibodies (EMA) [34,35].
The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases – coeliac disease and autoimmune atrophic gastritis – they have radically changed gastroenterologists’ diagnostic ability, while in others – autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis – their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits.
Celiac disease diagnosis in 2008
2008, Archives de Pediatrie
La mise au point et l’utilisation généralisée, depuis les années 1990, de tests sérologiques de plus en plus spécifiques et sensibles ont complètement transformé les conditions du diagnostic de la maladie cœliaque (MC) dont la forme active, symptomatique, n’est plus que le sommet émergé de l’iceberg qui la représente. Cliniquement, la maladie est soit évoquée devant des symptômes digestifs mineurs à l’âge habituel, soit dépistée dans la fratrie d’un cas index ou chez un enfant à risque (diabétique par exemple) à un âge plus avancé grâce à l’utilisation des anticorps anti-endomysium et antitransglutaminase tissulaire d’isotype IgA dont la sensibilité et la spécificité dépassent 90 %. Dans certains cas, le typage HLA apporte une aide au diagnostic en excluant un malade qui n’est ni DQ2 ni DQ8. L’« étalon or » du diagnostic demeure la biopsie intestinale qui le confirme en mettant en évidence l’atrophie villositaire de moins en moins souvent sévère, en particulier chez les malades dépistés. La confrontation des données cliniques, biologiques et histologiques est alors nécessaire pour affirmer la MC. Une fois le diagnostic établi, la maladie pourra être classée en MC active, silencieuse (sérologies positives et lésions histologiques isolées) ou latente (sérologies positives mais histologie normale) et l’attitude thérapeutique adaptée.
Since the 1990's, the widespread use of very sensitive and specific serological tests has completely changed the conditions of the diagnosis of celiac disease (CD). The active form of the disease is now only the tip of the iceberg representing it. Currently, CD is evoked either in front of mild digestive symptoms at the usual age or in the course of screening in siblings of an index case or in patients at risk (insulin dependent diabetes for example) at a later age using IgA anti-endomysium or anti-tissue transglutaminase antibodies, the sensitivities and specificities of which exceed 90%. In some cases, HLA typing is helpful in allowing to exclude a patient who is neither DQ2 nor DQ8. The intestinal biopsy remains the “gold standard” of the diagnosis showing villous atrophy; the latter, however, is less and less often severe as the disease is milder and milder. The diagnosis of CD then rests on the confrontation of the clinical, biological and histological data. Once CD has been diagnosed, it can be classified either as active or silent (positive serology with isolated villous atrophy), or latent (positive serology with a normal mucosa) and the appropriate therapeutic decision can be taken.
IL-15 drives the specific migration of CD94+ and TCR-γδ+ intraepithelial lymphocytes in organ cultures of treated celiac patients
2001, American Journal of Gastroenterology
Citation Excerpt :
This pathology is characterized by specific changes at the level of the small intestine with characteristic villus atrophy (2), intraepithelial lymphocytes infiltration (2), and production of anti-endomysium antibodies (4, 5). The antiendomysium antibodies have been considered to be a specific marker for disease (4–8) and reported to recognize tissue transglutaminase (9). Because gluten drives CD, simple gluten-free diet controls all the signs of this pathology.
OBJECTIVES:
Celiac disease (CD) is an under-diagnosed but extremely frequent disease, triggered by the ingestion of gliadin. The pathogenic mechanisms of CD are still poorly understood, but intraepithelial lymphocytes are considered to have a key role. We intended to define the subsets of T lymphocytes migrating upon gliadin challenge in organ cultures of treated celiac patients and establish the type of factor(s) driving such an infiltration.
METHODS:
Duodenum biopsies from 10 treated celiacs and 7 controls were cultured in vitro with/without gliadin digest (1 mg/ml) or interleukin (IL)-15 (10 ng/ml). In 7 treated celiacs IL-7, IL-4, and IL-2 were similarly tested. Intraepithelial CD3, CD8, TCR-γδ, and CD94 were detected by immunohistochemistry and numbered per mm epithelium.
RESULTS:
IL-15 but not IL-7, IL-4, or IL-2 induced intraepithelial increase of CD3+ and CD8+ cells in celiac and control intestine (p < 0.001 vs cultures with medium). IL-15 induced increases in the number of intraepithelial TCR-γδ+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was also effective in increasing intraepithelial TCR-γδ+ (but not CD94+) cells in celiac biopsies (p < 0.001). Gliadin induced intraepithelial migration of CD3+, CD8+ (p < 0.001), and CD94+ (p < 0.05) cells in celiacs, but not in controls.
CONCLUSIONS:
The results we describe in this report indicate that IL-15 might have a key role in modulating and driving intraepithelial infiltration and ultimately in the pathogenesis of CD.
Anti-endomysium, anti-reticulin and anti-gliadin antibodies and their use in the diagnosis of cœliac disease in the child
2001, Pathologie Biologie
Les anticorps anti-endomysium de classe IgA (AAE-IgA), les anticorps antiréticuline de classe IgA (AAR-IgA) et les anticorps antigliadine de classe IgA (AAG-IgA) ont été recherchés dans 120 sérums provenant de 120 enfants répartis en deux groupes : 60 enfants atteints de maladie cœliaque et 60 enfants n'ayant pas d'atrophie villositaire totale ayant servi de groupe contrôle. Les AAE sont recherchés par technique d'immunofluorescence indirecte (IFI) sur coupes de cordon ombilical humain. Les AAR sont recherchés par technique d'IFI sur coupes de rein foie et estomac de rat. Les AAG sont recherchés par technique immunoenzymatique ELISA. Chez les sujets ayant une MC, les sensibilités des AAE-IgA et AAR-IgA étaient de 86% et 76% respectivement. Leurs spécifités était de 100%. Quand l'âge du patient est strictement inférieur à deux ans, les sensibilités des AAE et AAR sont trop faibles, respectivement de 57% et 35%. Quand l'âge du patient est compris entre deux et 15 ans, la sensibilité était de 95% pour les AAE et 89% pour les AAR. Les AAG-IgA avaient une sensibilité et une spécificité de 86% et 83% respectivement. Ces résultats confirment, pour la population étudiée, que les AAE de classe IgA constituent un marqueur très intéressant pour le diagnostic de la MC de l'enfant et peuvent servir pour le dépistage de la MC dans la population à haut risque.
Coeliac disease is associated with gluten intolerance in genetically predisposed subjects. Environmental factors, particularly of viral origin, may also play a major role. In this study, the presence of IgA class anti-endomysium antibodies (AEA-IgA), IgA class anti-reticulin antibodies (ARA-IgA) and IgA class anti-gliadin antibodies (AGA-IgA) was investigated in 120 serum samples from 120 children (60 patients with coeliac disease and 60 control subjects). The AEA were detected by indirect immunofluorescence on sections of human umbilical cord. The ARA were also investigated by the same technique in rat kidney, liver and stomach. The AGA were determined by an enzyme-linked immunosorbent assay (ELISA). In the patients with coeliac disease, the sensitivity of AEA and ARA was 86% and 76% respectively. In both cases, the specificity was 100%. In children below two years of age, the sensitivity of AEA and ARA was too low, i.e., 57% and 35% respectively. In children aged between two and 15 years, the sensitivity of AEA and ARA was 95% and 89% respectively. The sensitivity of IgA class AGA was 86%, and their specificity was 83%. In this study population, these results show that IgA class AEA are interesting markers for the diagnosis of coeliac disease in the child, and could be used in screening for coeliac disease in a high-risk population.
The measurement of IgA and IgG transglutaminase antibodies in celiac disease: A comparison with current diagnostic methods
2000, Pathology
Celiac disease (CD) is an inflammatory disorder of the small intestine induced by cereal prolamins. The demonstration of IgA endomysial antibodies (EMA) is currently the most reliable serological screen for CD. The antigenic target is transglutaminase. The aim of this study was to develop an ELISA assay for the detection of antibodies to transglutaminase (TGA), and to assess the sensitivity and specificity of TGA for the detection of celiac disease against the benchmarks of jejunal biopsy, antigliadin antibodies (AGA) and EMA. Sera from 57 patients with celiac disease were tested for IgA and IgG TGA, IgA EMA, IgA and IgG AGA, and the total IgA level. The sensitivity, specificity, predictive value and concordance of AGA, EMA and TGA were assessed against the gold-standard biopsy result. IgG plus IgA TGA offered 100% sensitivity in CD patients for whom no dietary intervention had been commenced, with a specificity of 61%. The sensitivity of TGA dropped from 100 to 79% after dietary restriction. In patients on no gluten restriction, there was 100% agreement between TGA and EMA, and 100% agreement between TGA and AGA for the IgA isotype. The false-positive rate for TGA was 53% in Down’s syndrome patients and 25% in patients with systemic autoimmune disorders. We conclude that testing for TGA is a reliable diagnostic serology for celiac disease, with improved sensitivity compared with established methods. The results suggest that serial TGA measurements may be a more accurate marker for dietary compliance than AGA, but prospective studies are required.
Systematic review and meta-analysis: the incidence and prevalence of paediatric coeliac disease across Europe
2021, Alimentary Pharmacology and Therapeutics

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Original articleEvaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease

J Pediatr

J Pediatr

J Pediatr

Lancet

Lancet

Lancet

Lancet

Lancet

Lancet

Lancet

Is coeliac disease underdiagnosed?

Br Med J

Transient gastrointestinal disorders during infancy and early childhood: A follow-up study with special reference to coeliac disease

Acta Paediatr Scand

Reticulin antibody in children with malabsorption

Lancet

Original article
Evaluation of a serum IgA-class reticulin antibody test for the detection of childhood celiac disease