The association of
dermatitis herpetiformis (DH) with granular
IgA deposits at the dermal-epidermal junction and a
gluten sensitive enteropathy (GSE) suggests that a mucosal immune response may play an important role in the pathogenesis of DH. The degree of antigenic restriction, the
immunoglobulin class and subclass response to dietary
antigens, and the relationship of
antibodies against dietary
antigens to
IgA-containing circulating
immune complexes (CIC) in patients with DH, however, are not known. We have examined the serum of 33 patients with DH for
IgG and
IgA antibodies against
gliadin, and against 3
dietary proteins not thought to be related to GSE,
beta-lactoglobulin (beta-lacto), bovine
gamma globulin (BGG), and
casein. Eleven of 33 (33%) patients with DH had
IgA anti-
gliadin antibodies, whereas
IgA antibodies against beta-lacto were found in 11 of 33 patients (33%), against BGG in 15 of 32 (47%), and against
casein in 6 of 33 (18%); 17 of 32 (53%) patients had
IgA antibodies against one or more of these dietary
antigens. Significantly higher levels of
IgA antibodies were detected against beta-lacto (2,500 +/- 2,320 ng/ml, mean +/- SEM) and BGG (2,340 +/- 1,890 ng/ml) than
gliadin (1,250 +/- 851 ng/ml) in this group of antibody positive patients (p less than 0.05, Wilcoxon signed ranks test). Eleven of 17 patients with
IgA antibodies against dietary
antigens were found to have
IgA-containing CIC, whereas only one of the 15 antibody negative patients had
IgA-containing CIC (p = 0.0008, Fisher's exact test).
IgA anti-
gliadin antibodies were found to contain both
IgA1 and
IgA2 with a significantly increased proportion of
IgA2 when compared with the
IgA2 composition of the total serum
IgA (
IgA2: anti-
gliadin antibodies = 34 +/- 4.2%; total serum
IgA = 19 +/- 4.8%, p = 0.02, Students paired t test).
IgG antibodies against these
antigens were found to occur slightly more frequently in amounts not significantly greater than
IgA antibodies. This data demonstrates that a serum
IgA and
IgG antibody response to dietary
antigens occurs in approximately 50% of DH patients with a higher proportion of
IgA2 than total serum
IgA and does not appear to be restricted to
gliadin. This is significantly different from the pattern of cutaneous immunoreactants in patients with DH, and suggests that the deposition of
IgA in DH skin may be the result of an atypical mucosal immune response, a non-immunologic interaction of
IgA1 and DH skin, or arise from a non-mucosal source.