Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×–5.1× in the clinical cohort and 1.3×–4.9× in the family cohort, respectively. Using the assays’ own cut-offs (1×ULN) the PPVs ranged 84–100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower

Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×–5.1× in the clinical cohort and 1.3×–4.9× in the family cohort, respectively. Using the assays’ own cut-offs (1×ULN) the PPVs ranged 84–100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower

Serological diagnosis of celiac disease is accurate with different commercial tests

Uusi Käypä hoito -suositus mahdollistaa keliakiadiagnoosin asettamisen ilman ohutsuolen koepaloja kudostransglutaminaasivasta-aineiden ollessa >10x kynnysarvon (upper limit of normal, ULN) yhdessä positiivisten endomysiumvasta-aineiden (EmA) kanssa. Haasteena on markkinoilla olevilta useilta kaupallisilta testeiltä puuttuva standardisointi. Tutkimme, miten luotettavia erilaiset kaupalliset testit ovat serologiaan perustuvassa keliakiadiagnostiikassa aikuisilla. Tutkimuskohortti muodostui kahdesta keliakian ennakkotodennäköisyydeltään eroavasta ryhmästä. Korkean riskin tutkittavilla (n=239) potilailla oli vahva kliininen epäily ja kohtalaisen riskin ryhmässä (n=597) sukuriski keliakialle. Seeruminäytteet testattiin neljällä kaupallisella vasta-ainetestillä (Celikey, Orgentec, Eurospital ja Inova). Diagnoosit varmistettiin ohutsuolibiopsialla ja joissakin tapauksissa erikoistutkimuksilla. Lisäksi kaikilta määritettiin keliakiaan liittyvä HLA-DQ2/8 genotyyppi sekä EmA. Kliinisessä ryhmässä kaikkiaan 137 (57%) ja perheryhmässä 85 (14%) tutkimushenkilöä saivat keliakiadiagnoosin. Positiivinen ennustearvo (PPV) oli 100% (95% luottamusväli 78.1% – 100%) kaikille neljälle vasta-ainetestille molemmissa ryhmissä käytettäessä raja-arvoa 10x ULN. Ensimmäiset negatiiviset keliakialöydökset positiivisilla testituloksilla ilmaantuivat testistä riippuen kliinisessä ryhmässä välillä 1.0x – 5.1x ULN ja perheryhmässä välillä 1.3x – 4.9x ULN. Käyttämällä testien omia raja-arvoja (1x ULN) PPV vaihteli välillä 83.6 – 100%. Tutkimus osoitti kaikkien neljän vasta-ainetestin olevan varsin luotettavia käytettäessä nykyistä 10x ULN kriteeriä, mikä tukee uudistetun Käypä hoito -suosituksen toimivuutta keliakian diagnostiikassa. Etenkin osa testeistä toimi hyvin myös selvästi matalammilla ULN -kertoimilla. Mikäli löydös varmistetaan, se mahdollistaisi tähystystutkimusten vähentämisen entuudestaan.Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10× ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×–5.1× in the clinical cohort and 1.3×–4.9× in the family cohort, respectively. Using the assays’ own cut-offs (1×ULN) the PPVs ranged 84–100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10× ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower