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Biomedical subjects

Z M Falchuk

Publications and source records attributed to Z M Falchuk.

45 records · Page 3Linked to original sources

Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy.

HL-A phenotypes were determined in 24 unrelated patients with gluten-sensitive enteropathy (GSE) using a lymphocyte microcytotoxicity test. 21 of the 24 patients had HL-A8 in the second segregant series, a frequency of 0.875. In contrast, the HL-A8 frequency in 200 normal individuals was 0.215 (difference significant at P < 0.002), and in 6 patients with villous atrophy due to tropical sprue or hypogammaglobulinemia the HL-A8 frequency was 0.17 (difference from normal not significant). The HL-A types in the families of three HL-A8 positive patients with GSE indicated that the HL-A8 antigen was inherited as an autosomal dominant. Frequencies of the other HL-A antigens in the GSE group did not differ significantly from that of the normal group. These findings are compatible with the hypothesis that GSE is due to the presence of an abnormal "immune response (Ir) gene," leading to the production of pathogenic antigluten antibody or, alternatively, to the presence of a particular membrane configuration leading to the binding of gluten to epithelial cells with subsequent tissue damage.

Agammaglobulinemia↗

HL-A8: a genetic link between dermatitis herpetiformis and gluten-sensitive enteropathy.

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 marker 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.

Adult↗

Incorporation of L-leucine-14C into immunoglobulins by jejunal biopsies of patients with celiac sprue and other gastrointestinal diseases.

Incorporation of L-leucine-(14)C into proteins and immunoglobulins in vitro was determined in jejunal biopsy specimens from normal volunteers, patients with celiac sprue before and after introduction of gluten into the diet, patients with Whipple's disease in remission, and patients with immune deficiency states. Values for incorporation of L-leucine-(14)C into total and soluble protein by biopsies from five celiac sprue patients on a gluten-free diet were within, or slightly above, the 95% confidence limits for control data. One patient with celiac sprue and with normal intestinal histology had a normal value for incorporation into IgA; the other four patients with flat mucosas had elevated values. In Whipple's disease in remission, values for incorporation into total protein and IgA were within the control limits, whereas incorporation into soluble protein was increased. Patients with hypogammaglobulinemia or IgA deficiency had normal or elevated values for incorporation into total and soluble proteins; in these cases, however, no incorporation into IgA was detected. Biopsies from the four celiac sprue patients studied revealed that with introduction of gluten into the diet (a) incorporation into total protein, soluble protein, or both, increased; (b) incorporation into IgA increased in all patients, and in two instances the increase was greater than the increase in incorporation into total protein; and (c) incorporation into IgM increased in all patients. The changes during gluten administration usually occurred before changes in gastrointestinal absorptive function or in concentration of IgA in serum could be detected. These results indicate that gluten challenge stimulates increased local intestinal synthesis of immunoglobulins in patients with celiac sprue. The reaction occurs within days and it is possible that it plays a primary role in the pathogenesis of the disease.

Adult↗