Prediction of a clinical response to a therapy of a subject with an autoimmune disease based on B cell immune repertoire may include determining a plurality of clone frequencies in a biological sample from the subject, wherein the clone frequencies include: IgM, IgD, IgG3, IgG4, IgA, IgM with first somatic hypermutation (SHM) level, IgG1 with second SHM level. A plurality of decision criteria may be applied to features including the plurality of clone frequencies. Each decision criterion applies at least one threshold to a feature, wherein the plurality of decision criteria provides a plurality of output values. The plurality of output values may be summed and a sigmoid transformation may be applied to the summed value to form a prediction value. The prediction value may be compared to a final threshold to identify the subject as a likely responder or non-responder to an autoimmune disease therapy.