Serological Diagnosis of Celiac Disease –Moving Beyond the Tip of the Iceberg

Abstract

The majority of celiac disease affected patients are undiagnosed. Since the epidemiology and phenotype of CD is constantly changing towards latent, hyposymptomatic or asymptomatic behavior and since there is an increased risk of complications, early diagnosis and subsequent adherence to gluten-free diet is highly recommended. Multiple serological tests are on the market and the most frequently used test is IgA-tTG. This is not sensitive enough to be used alone, and combined tests enhance detection. Several combinations have been studied but not accurately compared to each other. The most frequently used combination is anti IgG-DGP with IgA-tTG, however, increasingly the new generation of anti neo-epitope DGP+tTG IgG+IgA is being used. At present, there is insufficient information to demonstrate that screening general populations definitely results in clinical benefit. However, asymptomatic individuals in high-prevalence groups should be screened.

Comparison of the Reliability of 17 Celiac Disease Associated Bio-Markers to Reflect Intestinal Damage

“…Our own experience [16,18,19] and that of many others [1] favors combination tests to screen for CD. The main single antigen ELISA kit candidates are anti-tTg IgA and anti-DGP IgG, competing with the new CeliCheck combination of IgA and IgG thus omitting screening for IgA deficiency [16,[18][19][20][21].…”

“…The majority of patients are still under-diagnosed, but increasing awareness and improved serological performances, raise the diagnostic yield. In contrast, in high-risk populations the average risk of CD can reach 5-10% [1]. In the last decades CD frequency is increasing, joining the surge in autoimmune disease incidence and prevalence worldwide [2,3].…”

“…All these changes make reliance on symptomatology more remote and therefore diagnosis of the disease more difficult [6]. Recent, major improvements in serological markers performance, with sensitivities and specificities above 90%, are an additional reason why serological screening of CD has achieved prime importance [1].…”

“…There are multiple serological tests on the market: IgA anti-endomysial antibody (EMA), IgA and/or IgG tissue transglutaminase (tTg), IgA and/or IgG deamidated gliadin peptide (DGP), whereby IgA-tTg is the most frequently used and ESPGHAN's recommended one. Several combination tests are available too: DGP IgA+G, tTg IgA+G, Gliadin IgA+G (check), CeliCheck IgA, IgG or IgA+IgG (autoantibodies against the cross-linked complex of tTg and gliadin peptides (tTg neo-epitope) and the recently described IgG and/ or IgA or IgG+IgA combined mTg neo-epitope and mTg (AESKULISA® mTg neo-epitope and mTg, RUO) [1]. Being a new serological biomarker of CD mTg neo-epitope deserves some background information.…”

GUT-the Trojan Horse in Remote Organs’ Autoimmunity

“…The result is neo-epitopes of gliadin docked on the tTg, inducing anti-tTg or anti neo-epitope tTg autoantibodies. These are the well-known serological markers of CD [21,22]. More recently, a family member of tTg, the microbial Tg that is heavily used in the food industry, has been shown to induce specific antibodies in CD patients [3,4,23].…”