Amelogenin specific IgA and IgG in children with untreated coeliac disease

Abstract

Children with untreated coeliac disease (CD) may develop enamel defects. Moreover, children with untreated CD have increased serum levels of gliadin reactive IgG, which may cross-react to amelogenin. The aim of this study was to investigate reactivity of anti-gliadin IgA and IgG to amelogenin in children with untreated CD. Blood samples from patients with CD (n = 75) and from disease controls (n = 24) were analysed for IgA and IgG reactivities to amelogenin (Emdogain) and to gliadin by ELISA. Whereas children with CD had statistically significantly higher serum levels of anti-amelogenin IgA, only those with the most severe CD (Marsh 3c) had significantly higher anti-amelogenin IgG immune reactivity than the disease controls. Western blotting confirmed that the IgA and IgG immune reactivity was to the amelogenin-specific bands in Emdogain and to a 22-kDa human recombinant amelogenin. Cross-inhibition studies revealed that the anti-amelogenin immune reactivity was not only caused by anti-gliadin cross-reactivity but also included amelogenin selective immune reactivity. Some controls had high levels of anti-amelogenin IgA and IgG, similar to children with CD. Thus, anti-amelogenin IgA and IgG may not only be involved in the aetiology of CD-associated enamel defects but may also interfere with enamel maturation in non-coeliac children.

Epitope mapping of anti‐amelogenin IgA in coeliac disease

“…Blood samples were taken from these children when the diagnostic jejunal biopsy was performed. The serum levels of anti-gliadin IgA were significantly lower in the biopsy-negative controls than in the children with biopsy-proven CeD, as reported previously (5). Diagnosis of CeD was based on anti-TG2 IgA levels, HLA genotypes, and clinical, histopathological, and immunohistochemical examination of jejunal biopsy samples.…”

“…The anti‐AMEL IgA titre was apparently associated with disease activity as the selected patients from the second cohort and CeD patients in the first cohort with severe jejunal villous atrophy (Grade 3c, Marsh–Oberhüber classification) had the highest anti‐AMEL IgA–peptide reactivity. Although anti‐AMEL IgA reactivity was not CeD specific, the titres were considerably lower and only two of the six CeD‐negative controls with highest anti‐AMEL IgA reactivity had sufficiently high anti‐peptide reactivity to be considered as positive for any single peptide, in contrast to 26 of the 32 CeD patients examined.…”

“…Patients with CeD have increased IgG and IgA to gliadin, but the titres of serum anti‐gliadin IgA are more closely associated with gluten ingestion, and fall more rapidly on a gluten‐free diet, than the titres of serum anti‐gliadin IgG . Only the levels of anti‐AMEL IgA (Emdogain) were significantly increased in CeD children compared with those in whom CeD was suspected but not confirmed . Similarly to IgG , serum IgA from CeD children, but not from controls, detected AMEL in secretory ameloblasts in situ , supporting its functional potential.…”

“…Several aetiological mechanisms may induce developmental enamel damage ; however, AMEL‐reactive antibodies may be involved in CeD‐associated developmental enamel defects. Patients with CeD have increased IgG and IgA to gliadin, but the titres of serum anti‐gliadin IgA are more closely associated with gluten ingestion, and fall more rapidly on a gluten‐free diet, than the titres of serum anti‐gliadin IgG .…”

“…Development of normal enamel reoccurs following treatment of active disease with a gluten‐free diet . We and others have reported that IgG and IgA to gliadin cross‐react with amelogenin (AMEL) (the abbreviation ‘AMEL’ is used for both amelogenin X and Y isoforms in this paper, unless referring to the specific X isoform of amelogenin, in which case the abbreviation ‘AMELX’ is used) in adults and paediatric subjects with untreated CeD. Thus, anti‐gliadin cross‐reactive antibodies may interfere with normal enamel maturation and induce CeD‐associated developmental enamel defects.…”