Diagnostic Accuracy of IgA Anti‐Tissue Transglutaminase Antibody Assays in Celiac Disease Patients with Selective IgA Deficiency

Abstract

Clinical studies have estimated a 10- to 20-fold increased risk for celiac disease (CD) in patients with selective IgA deficiency (SIgAD). For this reason, screening for CD is mandatory in SIgAD patients, but it represents a special challenge since the specific IgA class antibodies against gliadin (AGA), endomysium (EMA), and tissue-transglutaminase (tTG) are not produced in patients with CD. IgG class counterparts of these antibodies may be informative; in particular IgG EMA has been demonstrated to be a valid marker for diagnosing CD in SIgAD cases, but it is not used much in clinical laboratories, because it is cumbersome and involves some technical difficulties. Even if it was widely used in clinical laboratories, the measuring of IgG AGA has shown a less-than-optimum diagnostic accuracy, so that now it tends to be substituted by tests for anti-tTG IgG, for which the few available studies have shown diagnostic performances superior to AGA. Since it is not known whether various available methods for measuring IgG anti-tTG antibodies offer similar diagnostic performances, we have compared the results obtained from nine second-generation commercial methods (D-tek, Phadia, Immco, Orgentec, Radim, Euroimmun, Inova, Aesku, Generic Assays), measuring IgG anti-tTG antibodies in 20 patients with CD and SIgAD and in 113 controls (9 patients with SIgAD without CD, 54 patients with chronic liver disease, and 50 healthy individuals). Diagnostic sensitivity, calculated by means of ROC plot analysis, ranged between 75% and 95%, and specificity ranged from 94% to 100%. In the same population, the diagnostic sensitivity and specificity of AGA IgG were 40% and 87%, respectively. Even though they perform differently, all IgG anti-tTG methods evaluated are reliable serological assays for the diagnosis of CD in SIgAD patients, with diagnostic accuracy superior to the AGA IgG method. The methods that use a mix of tTG and gliadin peptides as the antigenic preparation have a specificity slightly lower than that of the methods that use only tTG.

Linee guida per la diagnosi di laboratorio e istologica della malattia celiaca. Revisione 2015

“…Oltre alle IgA, per gli anti-tTg può essere dosata anche la classe IgG [91,92], ma ne è sconsigliata la determinazione nei pazienti con normali livelli di IgA totali; tale dosaggio è invece fondamentale, assieme agli anticorpi anti-DGP IgG, nei soggetti con deficit assoluto di IgA [93,94].…”

Serum autoantibodies directed against transglutaminase-2 have a low avidity compared with alloantibodies against gliadin in coeliac disease

“…The frequency of IgA deficiency in CD patients is approximately 10%, compared with 1% in the normal population [16,17]. In these patients, IgG instead of IgA antibodies are used for diagnostic purposes and followup.…”

Hematological manifestations of celiac disease

“…First of all, patients with CD are more prone to gastrointestinal infections, which tend to be more severe since microorganisms are more likely to rapidly invade a damaged intestinal mucosa. The second implication lies in the fact that these patients may have a negative serology since specific IgA-class antibodies against gliadin, endomysium, and tissue transglutaminase are not produced in IgA-deficient patients, and IgA-secreting plasma cells are absent in intestinal biopsy specimens [69,71].…”