Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

Abstract

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.

Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis

“…Sensitive and accurate biosensing systems for these biomarkers can not only significantly aid in the early diagnosis and clinical management of AIDs but also help to establish therapeutic strategies [ 4 ]. Biosensors for the detection of autoantibodies specific to AIDs, including antiphospholipid syndrome (APS) [ 91 , 92 , 93 , 94 ], rheumatoid arthritis (RA) [ 95 , 96 , 97 , 98 , 99 ], systemic lupus erythematosus (SLE) [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ], multiple sclerosis (MS) [ 108 , 109 , 110 , 111 ], and celiac disease (CD) [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ], are now constructed based on diverse techniques with many advantages, including high sensitivity and easy operation.…”

“…Other techniques such as giant magnetoresistive (GMR) biosensor microarrays have been designed to analyze serum samples from SLE patients and have also been shown to be capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice [ 101 ].…”

Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors

“…We have developed magneto-nanosensors capable of monitoring multiple proteins at femtomolar sensitivities with a large dynamic range 16 , 17 . The magneto-nanosensors have been demonstrated for the detection of radiation biomarkers 18 , autoantibodies 19 , 20 , and small molecules 21 as well as for monitoring protein-protein interactions 22 , 23 . Here, we present a method using magneto-nanosensors with 6-plex cytokine assays to measure longitudinal protein profiles in response to cyclophosphamide treatment in mouse lymphoma models.…”

Giant magnetoresistive biosensors for real-time quantitative detection of protease activity

“…Second, the GMR sensors can be arrayed for multiplexed detection in a single assay without the need for optical scanning. Third, magnetic sensors are insensitive to the sample matrix, allowing them to be used with a wide variety of samples with minimal sample preparation 39 , making then convenient for use in point-of-care (POC) or point-of-use (POU) settings 40 . Lastly, the sensors continuously quantify the local magnetic field changes enabling real-time monitoring of the assay.…”