Autoantibody Reversion: Changing Risk Categories in Multiple-Autoantibody–Positive Individuals

OBJECTIVE Most individuals with two or more islet autoantibodies progress to clinical type 1 diabetes. However, in some individuals, autoantibodies are subsequently lost. Here, our objectives were to determine the frequency of autoantibody loss (reversion) in multiple-autoantibody–positive individuals and to determine the association between reversion and progression to clinical disease. RESEARCH DESIGN AND METHODS We analyzed multiple-autoantibody–positive individuals participating in TrialNet’s Pathway to Prevention Study for reversion and determined the effect of reversion on progression to clinical disease using a Cox regression analysis. RESULTS Of 3,284 multiple-autoantibody–positive subjects, reversion occurred in 134 (4.1%) and was associated with reduced incidence of clinical disease. Reversion occurred more frequently with older age, lower autoantibody titers, and fewer positive autoantibodies. CONCLUSIONS Although reversion of multiple-autoantibody positivity is rare, when it occurs, the risk of progressing to clinical disease is reduced. This suggests unknown mechanisms promoting immune remission in some individuals.