Comparison of the intestinal and serum antibody response in patients with dermatitis herpetiformis

Abstract

Dermatitis herpetiformis (DH) is an intensely pruritic, blistering skin disease characterized by cutaneous IgA deposits and an associated, most often asymptomatic, glutensensitive enteropathy. When patients with DH are placed on a gluten-free diet both the intestinal abnormality and the cutaneous manifestations of the disease are controlled, suggesting that a mucosal immune response is important in the pathogenesis of DH. Although patients with DH continue to ingest gluten only 40–50% have evidence of an ongoing mucosal immune response in their serum. In order to investigate directly the mucosal immune response in patients with DH the antibody response to dietary antigens was analyzed in intestinal secretions and compared to that found in the serum. Intestinal secretions from six patients with DH and five normal subjects were collected using an intestinal lavage solution and analyzed for total IgA, IgG, IgM, and IgA subclasses, and for IgG, IgA, and IgM antibodies against the dietary antigens bovine β-lactoglobulin and gliadin. Intestinal secretions from patients with DH contained more IgA than those from normal subjects (mean total IgA: DH = 2.3 mg/ml; normal subjects (NL) = 0.143 mg/ml, P = 0.017). This increase in IgA in intestinal secretions from patients with DH was composed primarily of IgA 1 (intestinal IgA: 86% IgA 1, 14% IgA 2; NL gut secretions: IgA 1 = 54%; IgA 2 = 46%). Increased IgA antibodies directed against β-lactoglobulin and gliadin were detected in gut secretions of two of six patients with DH and in none of the normal subjects. Serum IgA antibodies against β-lactoglobulin and gliadin were detected only in the two subjects who had detectable IgA antibodies in their intestinal secretions. Serum and intestinal IgA anti-β-lactoglobulin antibodies had similar isoelectric spectrotypes (p I 5.0–6.5), IgA subclass composition, and antigenic reactivity by immunoblot analysis, demonstrating the close relationship between the serum and intestinal IgA antibodies. These data demonstrate that in patients with DH an ongoing mucosal immune response is present in the gut as evidenced by a significantly increased concentration of IgA, predominately IgA 1. The strong correlation between detectable serum and intestinal IgA antibodies against dietary antigens demonstrates that the lack of serum IgA antibodies against dietary antigens in some patients with DH is not due to the presence of “blocking” IgA anti-dietary antigen antibodies in intestinal secretions. The striking similarity of the serum and intestinal IgA antibodies when they are present suggests that serum IgA antibodies against dietary antigens found in patients with DH are of mucosal origin and that IgA of mucosal origin can persist in the sera of patients with DH.