Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermatitis herpetiformis (DH) is an intensely pruritic, blistering skin disease characterized by cutaneous IgA deposits and an associated, most often asymptomatic, gluten-sensitive 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 beta-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 IgA1 (intestinal IgA: 86% IgA1, 14% IgA2; NL gut secretions: IgA1 = 54%; IgA2 = 46%). Increased IgA antibodies directed against beta-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 beta-lactoglobulin and gliadin were detected only in the two subjects who had detectable IgA antibodies in their intestinal secretions. Serum and intestinal IgA anti-beta-lactoglobulin antibodies had similar isoelectric spectrotypes (pI 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 IgA1. 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.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of the intestinal and serum antibody response in patients with dermatitis herpetiformis. 172 78

Dermatitis herpetiformis (DH) is a pruritic papulovesicular skin disorder of unknown cause, characterized by granular IgA deposits in the dermis along the dermoepidermal junction. It is associated with gluten-sensitive enteropathy and increased IgA production by gut lymphoid tissue. We report four cases of immunologically documented DH studied by immunofluorescence technique. Monoclonal antibodies against the IgA subclasses IgA1 and IgA2 were used. IgA1 without IgA2 was found in the cutaneous deposits in each case. The IgA1 had both kappa and lambda light chains in approximately equal quantities. Because normal gut-associated lymphoid tissue produces 70% IgA1 and 30% IgA2, while circulating IgA is primarily IgA1, it could be concluded that the IgA in the skin of DH patients is not produced in the gut. However, the subclass restriction of the IgA produced by pathologic gut-associated lymphoid tissue is unknown. Alternatively, both IgA1 and IgA2 may be produced by the gut, but only IgA1 is involved in the production of cutaneous lesions.
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PMID:Dermatitis herpetiformis. Cutaneous deposition of polyclonal IgA1. 308 93

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.
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PMID:Characterization of the mucosal immune response to dietary antigens in patients with dermatitis herpetiformis. 325 98

Dermatitis herpetiformis (DH) is a chronic, blistering skin disease characterized in part by deposits of IgA at the dermal-epidermal junction. Eighty-five percent of DH patients have granular IgA deposits and have an associated gluten-sensitive enteropathy (GSE). In contrast, 15% of DH patients have a linear pattern of IgA deposits and no associated intestinal abnormality. Although circulating IgA antibodies against skin are not present in these patients, 40% of DH patients do have IgA-containing circulating immune complexes (IgA-CIC). The role and origin of the cutaneous IgA and the IgA-CIC in patients with DH are unknown; however, the association of GSE with the granular IgA deposits suggests that a mucosal immune response may be important in the pathogenesis of DH. We have characterized the IgA subclass composition of the cutaneous IgA deposits in patients with DH, and have isolated and characterized the IgA-CIC from these patients. Twenty-nine of 29 patients with DH and granular IgA deposits were found to have only IgA1 deposits. Ten of 11 patients with linear IgA deposits also had only IgA1 deposits; one of 11 had IgA2 deposits. Isolated IgA-CIC from the sera of eight patients with DH and granular IgA deposits were found to contain both IgA1 (58% +/- 5, mean percent of total IgA +/- SEM) and IgA2 (42% +/- 5), as were IgA-CIC from two patients with ordinary GSE without cutaneous IgA deposits. The IgA subclass composition of the isolated immune complexes was significantly different from the serum IgA1 and IgA2 composition (serum IgA1 = 76% +/- 6; IgA2 = 24% +/- 5, p less than 0.025, Student's t-test), and suggests that the IgA-CIC may arise from gut-associated lymphoid tissue (GALT). Sequential anti-IgA1 absorption of serum which contained IgA-CIC did not remove all the IgA-CIC, suggesting that the complexes circulate as separate IgA1 and IgA2 complexes. The finding of IgA1 alone in the skin of patients with DH suggests that the cutaneous IgA may not arise from GALT, or that IgA1, possibly arising in GALT, is preferentially bound to DH skin. Because IgA-containing CIC which contain both IgA1 and IgA2 were found in the serum of patients with DH and with ordinary GSE, it seems unlikely that IgA-containing CIC are responsible for the cutaneous IgA deposits seen in DH.
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PMID:Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. 402 Jan 33

Dermatitis herpetiformis (DH) or Duhring-Brocq disease is a chronic bullous disease characterized by intense itching and burning sensation in the erythematous papules and urticarial plaques, grouped vesicles with centrifuge growth, and tense blisters. There is an association with the genotypes HLA DR3, HLA DQw2, found in 80-90% of cases. It is an IgA-mediated cutaneous disease, with immunoglobulin A deposits appearing in a granular pattern at the top of the dermal papilla in the sublamina densa area of the basement membrane, which is present both in affected skin and healthy skin. The same protein IgA1 with J chain is found in the small intestinal mucosa in patients with adult celiac disease, suggesting a strong association with DH. Specific antibodies such as antiendomysium, antireticulina, antigliadin and, recently identified, the epidermal and tissue transglutaminase subtypes, as well as increased zonulin production, are common to both conditions, along with gluten-sensitive enteropathy and DH. Autoimmune diseases present higher levels of prevalence, such as thyroid (5-11%), pernicious anemia (1-3%), type 1 diabetes (1-2%) and collagen tissue disease. The chosen treatment is dapsone and a gluten-free diet.
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PMID:Review: dermatitis herpetiformis. 2406 31