Genetic, morphometric and immunohistochemical markers of latent coeliac disease

It is recognized that coeliac disease may exist in a latent form characterized by HLA-DR3 and increased counts of intra-epithelial lymphocytes (IELs) and gamma/delta T cells in jejunal biopsies. To determine whether subjects with persistent serological markers 4 and 13 years after a population screening survey have the HLA constitution of coeliac disease and/or minor morphometric abnormalities of the small intestine, including raised gamma/delta T-cell counts, as possible indicators of latent coeliac disease.

Participants with positive serology detected by the Belfast MONICA Project surveys (1983 and 1991) were subdivided into those with persistently positive serology (persistent serology), negative serology at follow-up (transient serology) and those with enteropathy (coeliac disease). Morphometric features were compared with MONICA controls who had negative serology and HLA antigen frequencies were compared with blood donor controls.

Subjects were followed up in 1994-1996 and were re-tested for IgA antibodies to gliadin, endomysium and reticulin. HLA typing was carried out and IELs and gamma/delta T-cell counts were assessed in jejunal biopsies in subjects who gave consent.

Persistent serology mainly concerned antigliadin (AGA) and antireticulin (ARA) antibodies but one patient had positive antiendomysial antibody (EMA) and ARA in 1983, which became negative at follow-up, at which time they were positive for AGA. No significant differences were observed between IELs or gamma/delta T-cell counts when the persistent and transient groups were compared in turn with the MONICA controls. HLA-DR2 was expressed in 11 of 16 in the persistent group compared to 47 of 150 blood donor controls (P = 0.013). HLA-DR3 occurred in 15 of 17 coeliac patients compared to 37 of 150 blood donors (P = 0.00001).

Persistent serological markers following population screening do not appear to indicate latent coeliac disease.