Influence of Age and Genetic Risk on Anti‐tissue Transglutaminase IgA Titers

Vécsei, Andreas; Arenz, Tina; Heilig, G; Arenz, Stefan; Bufler, Philip; Koletzko, Sibylle

doi:10.1097/mpg.0b013e31818c5ff6

Cited by 12 publications

(12 citation statements)

References 24 publications

(27 reference statements)

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“…Given clinical suspicion of CD without prior antibody test [7]–[9] prevalence ranges between 3 to 10%. Down to this prevalence, the diagnostic procedures presented here yield reliable results.…”

Section: Discussionmentioning

confidence: 99%

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Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

Wolf

Hasenclever

Petroff³

et al. 2014

PLoS ONE

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Diagnosis of coeliac disease (CD) relies on a combination of clinical, genetic, serological and duodenal morphological findings. The ESPGHAN suggested that biopsy may not be necessary in all cases. New guidelines include omission of biopsy if the concentration of CD-specific antibodies exceeds 10 times the upper limit of normal (10 ULN) and other criteria are met. We analysed the 10 ULN criterion and investigated multiple antibody-assays. Serum was collected from 1071 children with duodenal biopsy (376 CD patients, 695 disease-controls). IgA-antibodies to tissue transglutaminase (IgA-aTTG), IgG-antibodies to deamidated gliadin peptides (IgG-aDGL) and IgA-endomysium antibodies (IgA-EMA) were measured centrally. We considered 3 outcomes for antibody test procedures utilizing IgA-aTTG and/or IgG-aDGL: positive (≥10 ULN, recommend gluten-free diet), negative (<1 ULN, no gluten-free diet) or unclear (perform biopsy). Positive (PPV) and negative (NPV) predictive values were based on clear test results. We required that they and their lower confidence bounds (LCB) be simultaneously very high (LCB >90% and PPV/NPV >95%). These stringent conditions were met for appropriate antibody-procedures over a prevalence range of 9–57%. By combining IgG-aDGL with IgA-aTTG, one could do without assaying total IgA. The PPV of IgG-aDGL was estimated to be extremely high, although more studies are necessary to narrow down the LCB. The proportion of patients requiring a biopsy was <11%. The procedures were either equivalent or even better in children <2 years compared to older children. All 310 of the IgA-aTTG positive children were also IgA-EMA positive. Antibody-assays could render biopsies unnecessary in most children, if experienced paediatric gastroenterologists evaluate the case. This suggestion only applies to the kits used here and should be verified for other available assays. Confirming IgA-aTTG positivity (≥10 ULN) by EMA-testing is unnecessary if performed on the same blood sample. Prospective studies are needed.

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Section: Discussionmentioning

confidence: 99%

“…The studies cited above were based on very high prevalence of up to 100%. However, pre-test probability in symptomatic patients in clinical practice may be as low as 3 to 10% [7]–[9]. Studies on the performance of antibody assays at higher cut-offs in the diagnosis of CD in children are still rare.…”

Section: Introductionmentioning

confidence: 99%

Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

Wolf

Hasenclever

Petroff³

et al. 2014

PLoS ONE

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“…The same report showed the centralized hospital ELISA TG2-IgA in 11/15 studies to have a sensitivity of >90% and in 13/15 studies a specificity of >90%. ELISA testing for the presence of TG2-IgA seems to lead to false-positive results especially in individuals carrying a high risk of CD such as relatives of patients [31]. As reviewed by Husby et al [24], TG2-IgA positivity without CD is also seen in autoimmune disorders, in patients with infections, tumors, psoriasis and heart and liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Fingertip rapid point-of-care test in adult case-finding in coeliac disease

Popp

Jinga

Jurcuţ³

et al. 2013

BMC Gastroenterol

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BackgroundCoeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose.MethodsAs CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects.ResultsIn on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive.ConclusionThe fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.

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“…Etwa 25-35 % der Bevölkerung sind positiv für HLA-DQ2 oder -DQ8. Allerdings kann bei negativem Nachweis von HLA-DQ2 und -DQ8 eine Zöliakie weitgehend (zu etwa 95-100 %) ausgeschlossen werden [15,29]. Bei den neuesten ESPGHAN-Diagnosekriterien haben sie einen größeren Stellenwert ( [15]; .…”

Section: Humane Leukozytenantigeneunclassified

Aspekte der Zöliakie im Kindes- und Jugendalter

Keller

2015

Gastroenterologe

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Influence of Age and Genetic Risk on Anti‐tissue Transglutaminase IgA Titers

Abstract: The influence of age and genetic predisposition/risk has to be taken into account when interpreting tTG results.

Cited by 12 publications

References 24 publications

Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls

Fingertip rapid point-of-care test in adult case-finding in coeliac disease

Aspekte der Zöliakie im Kindes- und Jugendalter

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