There is emerging evidence that autoantibodies directed against cytokines modulate the severity of autoimmune disease. Identification of cytokine-targeted autoantibodies in patients can be informative for diagnosis and predicting clinical outcome. In this issue of the JCI, Price and colleagues used a multiplex protein microarray to identify autoantibodies in serum from SLE patients. They found autoantibodies directed against the B cell-activating factor (BAFF) were associated with greater disease severity. This study highlights the contribution of cytokine-directed autoantibodies in disease and describes a valuable tool for identifying autoantibodies against serum antigens.