No abstract

In a previous study of the role of immunological processes in the pathogenesis of gluten-sensitive enteropathy, we demonstrated that the intestinal mucosa of patients with this disorder responds to gluten challenge in vivo with a striking increase in IgA and IgM synthesis (Loeb, Strober, Falchuk, and Laster, 1971). If this increase were causally related to the lesion of gluten-sensitive enteropathy, we might expect a certain portion of the post-challenge immunoglobulin to have antigliadin activity. In the present investigation, we have evaluated this possibility by first measuring jejunal immunoglobulin (IgA and IgM)synthesis inbiopsy specimens obtained from patients with gluten-sensitive enteropathy before and after a gluten challenge, and then measuring the fraction of this increase due to the synthesis of antigliadin antibody. The results indicate that biopsies from patients in remission do not produce antigliadin antibody, whereas biopsies from the same patients in exacerbation produce increased quantities of immunoglobulins, a large portion of which are antigliadin antibodies. 'Presented in part at the national meeting of the American

A B S T R A C T Histocompatibility antigen HL-A8 was found in 58% of 26 patients with dermatitis herpetiformis (DH) compared to 24% of a normal group. This difference in antigen frequency is significant at the P < 0.003 level. In a previous study, the frequency of this same genetic xnarker was found to be significantly increased in patients with gluten-sensitive enteropathy (GSE) (88% in patients vs. 22% in controls). The finding of an increased incidence of the HL-A8 antigen in both DH and GSE supports the concept that these diseases are related and provides a genetic basis for the association between the two.

Immunologic abnormalities have been described recently in patients with cystic fibrosis (CF). We have evaluated local IgA production by jejunal mucosa in vitro in seven patients with CF, seven patients with hereditary pancreatitis (HP), and 29 normal subjects. IgA synthesis in biopsy specimens was assessed by measuring 14C-L-leucine incorporation into IgA. Pancreatic enzymes were absent in all CF patients, and in two of seven HP patients; in four HP patients enzyme levels were reduced to 20% of normal. The mean IgA incorporation value in CF patients was 20,373 ± 9,244 cpm/mg protein (mean ± SD), and in HP patients was 11,403 ± 4,585, both values significantly greater than normal (6,688 ± 2,449) (p µ 0.001). In addition, the mean IgA incorporation value in CF patients was greater than the value in HP patients. (p µ 0.05). Within each patient group there was no correlation between IgA incorporation values and serum IgA levels, age, Shwachman score, severity of lung disease, type of bacteria in sputum cultures, or roentgenographic abnormalities of the small bowel. The most reasonable explanation for the findings is that patients with CF and HP are under an increased local antigenic stimulus, perhaps due to an altered gastrointestinal environment which leads to increased local IgA production.