Shared and unique immune alterations in pre-clinical autoimmunity

•Autoantibody accrual, specificity, and epitope spreading precede disease transition.•Plasma cytokines first increase preclinically, before autoantibody seroconversion.•Type II IFN is linked to initial loss of self-tolerance in many autoimmune diseases.•Type I IFN signatures precede symptoms in a subset of patients.•Preclinical cytokine and autoantibody elevations likely reflect immune dysregulation in mucosa, tissues and/or lymphatics.