High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health Physical Science Oncology Center (U54CA143907), the Center for Cancer Nanotechnology Excellence (U54CA151459), a Sanofi BioSTAR seed grant (through Stanford Bio-X program), and the Autoimmunity Center of Excellence (ACE, 1U19AI110491) at Stanford. Dr. Utz is the recipient of a Donald E. and Delia B. Baxter Foundation Career Development Award, gifts from the Floren Family Trust and Ben May Charitable Trust, and support from the NHLBI (Proteomics Contract 268201000034C), NIH (grant numbers T32GM007365, U19-AI082719, U19-AI110491, UH2-AR067676, UM2-AR067678, UM1-AI110498, and U19-AI090019), and the Alliance for Lupus Research (grant number 21858). The Hopkins Lupus Cohort was funded by the NIH (RO-1 AR43727). This work was also supported in part by NIAMS (N01-AR-1-2256), the NIH (AR-43727), and a grant from the Lupus Research Institute. Dr. Haddon was funded by the Canadian Institutes for Health Research (CIHR Fellowship). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261382.