Abstract
Introduction and Objective: In TrialNet's Pathway to Prevention (PTP) study, SAB positive (SAB+) individuals develop stage 3 T1D at a rate of ~3%/year. Limited data on SAB reversion to negative (SAB-) in a non-birth cohort exists. Here, we aimed to identify the features and risk of progression to clinical T1D of SAB who revert. Methods: We grouped PTP participants with confirmed SAB+ (i.e., those who tested positive for the same antibody [Ab] on 2 consecutive visits) into reverters (tested negative on 2 subsequent, consecutive visits) or maintainers (had a subsequent SAB+ for the same SAB+). Glucose tolerance data were available for 84% of SAB+ and 81% of SAB-. Comparisons used Chi-square and T-tests. Results: Compared to SAB+ maintainers, SAB- reverters were younger (16.9±13.8 vs. 21.1±13.9, p<0.001); more likely to be Hispanic/Latino (16.7 vs 11.2%, p=0.012); less likely to be GADA+ (55.7 vs 72.9%, p<0.001), and more likely to be IA2A+ (7.6 vs 2.5%, p<0.001) or MIAA+ (36.7 vs 24.3%, p<0.001), Table 1. On follow-up, SAB- reverters did not progress to stage 3 T1D while 3.7% of SAB+ maintainers did (p=0.003); reverters were also less likely to progress to multiple Ab positivity. Conclusion: SAB- reverters have reduced risk of progression to stage 3 T1D compared to SAB+. Future work should aim to identify immunologic and metabolic protective mechanisms driving reversion.