Beta-cell Specific Autoantibodies: Are they Just an Indicator of Type 1 Diabetes?

Background: Autoantibodies (AAbs) against islet autoantigens (AAgs) are used for type 1 diabetes (T1D) diagnosis and prediction. Islet-specific AAbs usually appear early in life and may fluctuate in terms of number and titer sometimes for over 20 years before T1D develops. Whereas their predictive power is high for pediatric subjects with high genetic risk who rapidly progress to multiple AAb positivity, they are less reliable for children with low genetic risk, single AAb positivity and slow disease progression. Objective: It is unknown how AAbs develop and whether they are involved in T1D pathogenesis. So far an increase in AAb number seems to only indicate AAg spreading and progression towards clinical T1D. The goal of this review is to shed light on the possible involvement of AAbs in T1D development. Method: We thoroughly review the current literature and discuss possible mechanisms of AAb development and the roles they may play in disease pathogenesis. Results: Genetic and environmental factors instigate changes at the molecular and cellular levels that promote AAb development. Although direct involvement of AAbs in T1D is less clear, autoreactive B cells are clearly involved in various immune and autoimmune responses via antigen presentation, immunoregulation and cytokine production. Conclusion: Our analysis suggests that understanding the mechanisms that lead to islet-specific AAb development and the diabetogenic processes that autoreactive B cells promote may uncover additional biomarkers and therapeutic targets.