Combination testing for antibodies in the diagnosis of coeliac disease: Comparison of multiplex immunoassay and ELISA methods

Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Alimentary Pharmacology & Therapeutics (Impact Factor: 5.73). 09/2008; 28(6):805-13. DOI: 10.1111/j.1365-2036.2008.03797.x
Source: PubMed


Tissue transglutaminase (TTG) antibodies and newly developed deamidated gliadin peptide (DGP) antibodies have better accuracy than native gliadin antibodies. Multiplex immunoassay (MIA) measures multiple antibodies simultaneously providing a complete antibody phenotype with reduced turnaround time and cost.
To evaluate the agreement between MIA and enzyme-linked immunosorbent assay (ELISA) test results for coeliac autibodies in biopsy-proven coeliac patients and controls and to model the diagnostic utility of combination testing.
We compared the sensitivity, specificity and accuracy of MIA and ELISA methods for TTG and DGP antibodies in mainly adult untreated coeliac patients (n = 92) and controls (n = 124).
There was excellent agreement and a significant correlation between the results of MIA and ELISA methods (k > 0.8, r > 0.7) for all tests, except IgG. Diagnostic indices of individual and combination tests measured by the MIA method did not differ significantly from those measured by ELISA. The combination tests slightly increased sensitivity (if any test was positive) and specificity (if all tests were positive) compared to the individual tests.
Multiplex immunoassay testing for antibodies is as accurate as ELISA for coeliac disease diagnosis and has practical advantages over ELISA method. Rational combination testing can help identify patients who need intestinal biopsy and may reduce unnecessary biopsies.

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    • "In the present study, the sensitivity and the specificity of IgA a-DGP was similar to that of IgG a-DGP (97% vs 94% and 92% vs 93.6%). This results concord with those found by other authors [15] [17] [19] [22] [36], hence, the combination of both tests was interesting. In fact, a prospective study demonstrated that the combination of AtTG and IgG a-DGP gives the best results both in the screening and in the diagnostic of CD [28]. "
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    ABSTRACT: OBJECTIVES: To assess the usefulness of anti-deamidated gliadin peptides antibodies (a-DGP), in the diagnostic of celiac disease (CD). PATIENTS AND METHODS: One hundred and three untreated CD patients (67 children and 36 adults) and 36 celiac patients under gluten-free diet were studied. Two hundred and seventy-four subjects served as controls (114 healthy blood donors, 80 healthy children and 80 patients with primary biliary cirrhosis). a-DGP (IgG and IgA) and anti-tissue transglutaminase antibodies (AtTG) were detected by enzyme-linked immunosorbent assay (Elisa). Anti-endomysium antibodies (AEA) were detected by indirect immunofluorescence on human umbilical cord. RESULTS: The sensitivitiy of IgG and IgA a-DGP were 94% and 97% respectively, compared to 96% for AEA and AtTG. The specificity of a-DGP was 93.6% for IgG and 92% for IgA. The specificity of AEA and AtTG were 100%. The frequency of IgG and IgA a-DGP was significantly higher in patients with CD than in control group (94% vs. 4.4%, P<10(-7); 97% vs. 8%, P<10(-7)). The frequency of IgG a-DGP was the same in children and adult (94%). The frequency of IgA a-DGP were similar in children and adults (95.5% vs. 100%). CONCLUSION: Our study shows that a-DGP increases neither the sensitivity nor the specificity of AEA and AtTG.
    Full-text · Article · Mar 2012 · Gastroentérologie Clinique et Biologique
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    • "ARA or gliadin antibodies ( AGA ) are no longer used in clinical practice due to their low sensitivity and specificity . However , the new deamidated gliadin peptide ( DGP ) antibodies might in future prove to give reliable results ( Kaukinen et al 2007 ; Rashtak et al 2008 ) "
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    ABSTRACT: The purpose of this study was to evaluate subjective food-related gastrointestinal symptoms and their relation to cow’s milk by determining the genotype of adult-type hypolactasia, measuring antibodies against milk protein, and screening the most common cause for secondary hypolactasia, namely coeliac disease. The whole study group comprised 1900 adults who gave a blood sample for the study when they attended a health care centre laboratory for various reasons. Of these 1885 (99%) completed a questionnaire on food-related gastrointestinal symptoms. Study No. I evaluated the prevalence of adult-type hypolactasia and its correlation to self-reported milk induced gastrointestinal symptoms. The testing for hypolactasia was done by determination of the C/T-13910 genotypes of the study subjects. The results show that patients with the C/C-13910 genotype associated with adult type hypolactasia consume less milk than those with C/T-13910 and T/T-13910 genotypes. Study No. II evaluated the prevalence and clinical characteristics of undiagnosed coeliac disease in the whole study population with transglutaminase and endomysium antibodies and their correlation with gastrointestinal symptoms. The prevalence of coeliac disease was 2 %, which is surprisingly high. Serum transglutaminase and endomysium antibodies are valuable tools for recognising an undiagnosed coeliac disease in outpatient clinics. In the study No. III the evaluation of milk protein IgE related hypersensitivity was carried out by stratifying all 756 study subjects with milk related problems and randomly choosing 100 age and sex matched controls with no such symptoms from the rest of the original study group. In the study No. IV 400 serum samples were randomly selected for analyzing milk protein related IgA and IgG antibodies and their correlation to milk related GI-symptoms. The measurement of milk protein IgA, IgE or IgG (studies No. III and IV) did not correlate clearly to milk induced symptoms and gave no clinically significant information; hence their measurement is not encouraged in outpatient clinics. In conclusion, adult type hypolactasia is often considered the reason for gastrointestinal symptoms in adults and determination of the C/T-13910 genotypes is a practical way of diagnosing adult type hypolactasia in an outpatient setting. Undiagnosed coeliac disease, should be actively screened and diagnosed in order to apply a gluten free diet and avoid the GI-symptoms and nutritional deficiencies. Cow’s milk hypersensitivity in the adult population is difficult to diagnose since the mechanism in which it is mediated is still unclear. Measuring of cow’s milk protein specific antibodies IgE, IgA or IgG do not correlate with subjective milk-related GI-symptoms. Väitöskirjatyössä tarkasteltiin työikäisen väestön maidon käyttöön liitettyjä vatsavaivoja. Tutkimukseen osallistui 1900 pääkaupunkiseudun terveyskeskusten laboratorioissa asioinutta henkilöä, jotka antoivat tutkimustarkoitukseen verinäytteen. Heistä 1885 ( 99%) täytti kyselykaavakkeen ruokaan ja erityisesti maitoon liittyvistä vatsavaivoista. Tutkimuskokonaisuus koostui neljästä osiosta, joista ensimmäisessä tarkasteltiin aikuistyypin hypolaktasian diagnostiikassa käytettävän geenitestin korrelaatiota maidosta koettuihin vatsaoireisiin sekä maidon käyttöön. Toisessa osiossa tarkasteltiin keliakian, tavallisimman sekundaarisen aikuistyypin hypolaktasian aiheuttajan, esiintyvyyttä ja korrelaatiota noninvasiivisiin laboratoriotesteihin. Kolmannessa osiossa tarkasteltiin maitoproteiini IgE:n välittämän yliherkkyyden mahdollista osuutta maidosta koettuihin vatsaoireisiin aikuisilla ja neljännessä osiossa maitoproteiini IgA:n ja IgG:n korrelaatiota maidosta koettuihin vatsaoireisiin. Tutkimustuloksena oli, että ruokaan ja erityisesti maitoon liitetyt vatsaoireet olivat varsin yleisiä aikuisilla. Aikuistyypin hypolaktasiaan liittyvän C/C-13910 genotyypin omaavat käyttivät merkitsevästi vähemmän maitoa kuin C/T-13910 ja T/T-13910 genotyypin omaavat (korkea laktaasi aktiviteetti). Keliakian esiintyvyys oli 2 %, joka oli selkeästi korkea aiemmin todettuihin esiintyvyyksiin verrattuna. Keliakian dignosoimiseen käytetyt endomysium- ja kudostransglutaminaasivasta-ainemääritykset olivat luotettavia menetelmiä ko. taudin selvittämiseksi, jatkotutkimusten ohjelmoimiseksi ja edelleen gluteiinittoman ruokavalion aloittamiseksi. Maitoproteiini IgA, IgE ja IgG eivät korreloineet maidosta koettuihin vatsavaivoihin. Aikuisten maitoon liittyvien vatsaoireiden selvittelyyn ja seulontaan avohoidossa tulisi käyttää aikuistyypin hypolaktasian geenitestiä, kudostransglutaminaasi- tai endomysiumvasta-aineita keliakian poissulkemiseksi sekä maidotonta koedieettiä. Maitoproteiinispesifisistä immunoglobuliini A, E tai G määrityksistä ei sen sijaan ole tutkimuksen mukaan aikuisväestössä hyötyä, eikä niitä tulisi turhaan tehdä.
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