Natural history of celiac disease autoimmunity in a USA cohort followed since 1974

Background. The natural history and the possible changes of celiac disease (CD) prevalence over time are still unclear. Objectives. 1) To establish whether loss of tolerance to gluten may occur at any age; 2) to investigate possible changes of CD prevalence over time; and 3) to investigate CD-related co-morbidities. Methods. We analyzed 3,511 subjects with matched samples from 1974 (CLUE I) and 1989 (CLUE II). To avoid a selection bias regarding survival, we also screened 840 CLUE I participants who deceased after the 1974 survey. Outcome measure. CD autoimmunity (positivity to auto-antibodies) over time. Results. CD autoimmunity was detected in seven subjects in 1974 (prevalence 1:501) and in an additional nine subjects in 1989 (prevalence 1:219). Two cases of CD autoimmunity were found among the 840 subjects deceased after CLUE I. Compared to controls, untreated CD subjects showed increased incidence of osteoporosis and associated autoimmune disorders, but they did not reach statistical significance. Conclusions. During a 15-year period CD prevalence increased 2-fold in the CLUE cohort and 5-fold overall in the US since 1974. The CLUE study demonstrated that this increase was due to an increasing number of subjects that lost the immunological tolerance to gluten in their adulthood.