IgA Immune Response Patterns to Gliadin in Serum

Abstract

The incidence, titer and molecular size of anti-gliadin (GL) IgA were analyzed in sera from children with celiac disease (CD, n = 66), hospitalized control children (n = 64) and children with other malabsorption disorders (n = 103). Anti-GL IgA was assessed by solid-phase radioimmunoassay, and its molecular size was analyzed by sucrose density gradient ultracentrifugation. The median anti-GL IgA titer was significantly higher in untreated CD than in the other groups, with some overlap. Whereas 57% of anti-GL IgA were polymeric IgA (pIgA) in acute CD, only 17% were pIgA in children with other malabsorption disorders. These anti-GL pIgA consisted mainly of dimers with in some children, a low proportion of anti-GL secretory IgA (SIgA). A large proportion of anti-GL pIgA was associated with high total serum IgA. After the onset of a gluten-free diet (GFD), anti-GL pIgA disappeared more quickly from serum than mlgA. During the gluten challenge test, anti-GL IgA comprised 20% pIgA when they reappeared in serum, but 59% pIgA at the end of the test. The presence of anti-GL pIgA in serum seems related to chronic exposure to gluten of CD patients with a flat intestinal mucosa. These serum pIgA antibodies could result from a spillover from the intestinal mucosal synthesis into the circulation.

The changing immunological paradigm in coeliac disease

“…7, left) apparently explains most of the commonly increased serum IgA concentration characteristic of untreated or gluten-challenged patients [47]; a strong positive correlation exists between the serum level of IgA antibodies to gluten/gliadin and the number of jejunal IgA + PCs per tissue unit [34]. The fact that 57-61% of the circulating IgA antibodies are dimers in untreated patients [54,74], in addition to a substantial enrichment of the IgA2 antibody fraction [75], further attests to a significant mucosal origin. Alternatively, gluten/gliadin antibodies may be secreted in peripheral blood from circulating IgA + plasmablasts on their way from inductive gut-associated lymphoid tissue to seed the lamina propria [76].…”

Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.

“…There was no detectable secretion of pIgA unlinked to secretory component as shown by sucrose density gradient ultracentrifugation. Secretory component in perfusate samples of coeliac disease sedimented mainly with pIgA, but 14-4% (range 7-27) was excreted as free secretory component compared to 6-9% (range[4][5][6][7][8][9][10][11][12][13][14][15][16][17] in controls (p=0 05). The albumin and IgG secretion rates were similar in patients and control subjects.…”

Early impairment of gut mucosal immunity in HIV-1-infected children

“…[17]. Polymeric IgA and secretory IgA to gliadin have been described in this disease [18], and the IgAl isotype is predominant [19,20]. However, it was demonstrated that serum levels of antibodies to other dietary antigens are often increased in these patients [21].…”

“…The origin of serum secretory IgA antibodies and of IgA to dietary antigens has yet to be elucidated. They may represent antibodies produced locally in the gut mucosa spilling over into the circulation [18], but the preferential increase of IgAl suggests that they are produced in the bone marrow and in extraintestinal lymphoid tissue as the result of migration of locally stimulated lymphocytes [34] or of uptake of luminal antigens into the blood [35].…”