Secretion of celiac disease autoantibodies after in vitro gliadin challenge is dependent on small-bowel mucosal transglutaminase 2-specific IgA deposits

Abstract

Background: In celiac disease gluten, the disease-inducing toxic component in wheat, induces the secretion of autoantibodies which are targeted against transglutaminase 2 (TG2). These autoantibodies are produced in the smallintestinal mucosa, where they can be found deposited extracellularly below the epithelial basement membrane and around mucosal blood vessels. In addition, during gluten consumption these autoantibodies can also be detected in patients' serum but disappear from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The toxicity of gluten and the secretion of the disease-specific autoantibodies have been widely studied in organ culture of small-intestinal biopsy samples, but results hitherto have been contradictory. Since the mucosal autoantibodies disappear slowly after a gluten-free diet, our aim was to establish whether autoantibody secretion to organ culture supernatants in treated celiac disease patient biopsies is related to the duration of the diet and further to the preexistence of mucosal TG2-specific IgA deposits in the cultured biopsy samples.

Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease

“…More recently, similar data have been obtained measuring IgA anti-TG2 antibodies in supernatants of cultured biopsies from CD patients untreated and on a gluten-free diet [15][16][17]. This test has been proposed for diagnostic purposes, particularly in patients with normal mucosa.…”

“…Detection of anti-endomysium antibodies (EMA) and anti-TG2 IgA antibodies in faecal supernatants from CD patients was determined to be unreliable as a diagnostic test [25]. The search for anti-TG2 antibodies in culture supernatants of intestinal biopsy from CD patients by ELISA was proposed in particular to improve the accuracy of CD diagnosis in subjects with mild enteropathy and in patients negative for serum antibodies [15][16][17]. More recently, using immunofluorescence, Korponay-Szabo et al [7] showed that IgA deposited in the intestine of CD patients are directed against TG2.…”

“…Therefore, it is particularly important to find the most suitable assay to detect and measure these antibodies. In the last 20 years different assays have been used: measurement in faeces [23] or in intestinal fluids [24], search in supernatants of cultured biopsy fragments [11][12][13][14][15][16][17] or detection in the same biopsies of deposited antibodies [16], or expression in phage libraries of RNA, obtained from biopsies, coding for the antibodies [6,22]. Detection of anti-endomysium antibodies (EMA) and anti-TG2 IgA antibodies in faecal supernatants from CD patients was determined to be unreliable as a diagnostic test [25].…”

A Silent or Hypo-symptomatic Disease Can Erupt: Acute Presentations of Celiac Disease

“…We know nowadays that gluten or gliadin, when incubated with primary cultures of CD patients on glutenfree diet,induces morphological as well as immunological aberrations. Cytokine release, autoantibodies secretions, increased CD25+ cell density, MHC class 1chain-related gene A expression were reported [43,44]. Applying genetic bioinformatics, it was shown that important dysfunction of pathogenic networks related to cell to cell communications, intracellular signaling, ubiquitin-proteasome system, cell cycle and apoptosis and extracellular matrix modulation resulted from acute gliadin effects on mucosal biopsies of CD patients, while on gluten withdrawal [45].…”

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: Anti- Transglutaminase 2 Autoantibodies: Friends or Enemies

“…In IgA-deficient patients, these mucosal autoantibodies appear in the IgM-class instead. Their secretion in vitro on gliadin challenge is dependent on their mucosal deposits [16]. The measurement of ABs secreted into intestinal biopsies cultured supernatants has higher sensitivity and specificity than the detection of mucosal deposits and they can predict evolution towards mucosal atrophy [17].…”