Studies on the pathogenesis of coeliac disease
Simpson, F. Graham
Results of the Leucocyte Migration Inhibition (LMI) test with gluten in adult coeliac disease are shown to be affected by the histocompatibility antigen HLA-B8. Normal subjects with B8 show greater immunity than those lacking B8 and give similar results to untreated coeliacs. B8 and non-B8 coeliacs give similar results. A gluten-free diet produces an early increase in immunity in coeliacs with a later decline. Production of migration inhibitory factors in blood and by jejunal mucosa are inversely correlated. Untreated coeliacs give positive responses in the LMI test to several dietary antigens similar in magnitude and prevalence to those seen with gluten. These responses are uninfluenced by HLA-B8 and do not increase after gluten exclusion. Results of the LMI test with gluten are unaffected by puromycin and results of the test performed with purified polymorphs are similar to and correlate with results of the standard test. Added T lymphocytes have no effect. These results contrast with those seen with PPD as antigen. Normal leucocytes can be sensitised to gluten by coeliac serum and this sensitisation can be blocked by IgG, suggesting that migration inhibition is mediated by cytophilic antibody and not T cell produced lvmphokines. Jejunal mucosal biopsies from treated coeliac patients are co-cultured with autologous blood mononuclear cells. These biopsies show no significant damage with gluten or lymphocytes alone but quantitative histology shows evidence of toxicity when biopsies are cultured with gluten and lymphocytes together. Phosphatidyl inositol turnover in cultured biopsies is measured to try and detect a lectin-like effect of gluten but shows no difference between coeliacs and controls. The findings are discussed and the relevant literature is reviewed.