Avidity progression of dietary antibodies in healthy and coeliac children

Abstract

SUMMARYIn most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. b -lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against b -lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against b -lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-b -lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

Affinity maturation of immunoglobulin A anti-tissue transglutaminase autoantibodies during development of coeliac disease

“…Saalman et al [29] also observed that the avidity of IgG-AGA was preserved during remission on a gluten-free diet, despite a marked decrease in serum antibody concentration. Upon gluten challenge, most children showed a further increase in antibody avidity together with an elevated IgG-AGA level.…”

“…In type 1 diabetes, affinity maturation seems to be dependent on the antigen specificity of the autoantibodies [28]. Also in CD, there is evidence of avidity maturation of diseaseassociated antibodies, as Saalman et al [29] showed that IgG antibodies to gliadin (IgG-AGA) and b-lactoglobulin in children with untreated CD were of higher avidity than corresponding antibodies from healthy children. In addition, Vainio et al [30] have reported significantly increased amounts of high-avidity IgA gliadin antibodies (IgA-AGA) during prolonged experience of the CD-associated condition dermatitis herpetiformis.…”

“…We studied previously the avidity maturation of autoantibodies against the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes, but were not able to distinguish genetically predisposed prediabetic children from high-risk children remaining healthy on the basis of autoantibody avidity [28]. To our knowledge, investigations of affinity maturation of CD-associated antibodies have been focused hitherto on antibodies to dietary gliadin [29]. In this report, we studied the avidity maturation of autoantibodies against tissue transglutaminase, both in children progressing to CD and in subjects remaining healthy despite occasional presentation of IgA-TGA.…”

“…Saalman et al [29] investigated the avidity maturation of IgG class antibodies to gliadin (IgG-AGA) and b-lactoglobulin during early childhood using a thiocyanate elution assay, and found that the avidities of these two dietary antibodies increased with age both in healthy children as well as in children with untreated CD. The process seemed to be accelerated in the latter group, as gliadin and b-lactoglobulin antibodies in children with untreated CD showed significantly higher avidities than those of healthy children of the same age.…”

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

“…The elution method with the chaotropic agent sodium thiocyanate (NaSCN) has been described in previous publications [12][13][14]. For determination of antibody avidity, the serum dilution giving 50% of the maximum signal was determined by means of serial dilutions, as described above, and was used in a subsequent ELISA to determine avidity.…”