Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus.
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.
Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Jung-Rok
JR
Lee
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.
D James
DJ
Haddon
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.
Hannah E
HE
Wand
Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, California, USA.
Jordan V
JV
Price
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.
Vivian K
VK
Diep
Department of Electrical and Computer Engineering, University of California, San Diego, California, USA.
Drew A
DA
Hall
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Michelle
M
Petri
Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Emily C
EC
Baechler
Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, California, USA.
Imelda M
IM
Balboni
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, USA.|Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA.
Paul J
PJ
Utz
Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.|Department of Electrical Engineering, Stanford School of Engineering, Stanford, California, USA.
Shan X
SX
Wang
D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015374:Biosensing Techniques / Q000379:methods*; D016022:Case-Control Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007372:Interferons / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D040081:Protein Array Analysis / Q000379:methods*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; D007372:Interferons