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      Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

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          Abstract

          Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

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          Most cited references45

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          Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients.

          Description of the various autoantibodies that can be detected in patients with systemic lupus erythematosus (SLE). A literature review, using the terms "autoantibody" and "systemic lupus erythematosus", was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity, or other clinical associations. One hundred sixteen autoantibodies were described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 116 autoantibodies. SLE is the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of polyclonal B cell activation, impaired apoptotic pathways, or the outcome of idiotypic network dysregulation.
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            Printing proteins as microarrays for high-throughput function determination.

            Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins. To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins. A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities. The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution. Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules.
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              Taming lupus-a new understanding of pathogenesis is leading to clinical advances.

              Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the loss of tolerance to nuclear self antigens, the production of pathogenic autoantibodies and damage to multiple organ systems. Over the years, patients with SLE have been managed largely with empiric immunosuppressive therapies, which are associated with substantial toxicities and do not always provide adequate control of the disease. The development of targeted therapies that specifically address disease pathogenesis or progression has lagged, largely because of the complex and heterogeneous nature of the disease, as well as difficulties in designing uniform outcome measures for clinical trials. Recent advances that could improve the treatment of SLE include the identification of genetic variations that influence the risk of developing the disease, an enhanced understanding of innate and adaptive immune activation and regulation of tolerance, dissection of immune cell activation and inflammatory pathways and elucidation of mechanisms and markers of tissue damage. These discoveries, together with improvements in clinical trial design, form a platform from which to launch the development of a new generation of lupus therapies.
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                Author and article information

                Contributors
                Journal
                Genomics Proteomics Bioinformatics
                Genomics Proteomics Bioinformatics
                Genomics, Proteomics & Bioinformatics
                Elsevier
                1672-0229
                2210-3244
                28 September 2015
                August 2015
                28 September 2015
                : 13
                : 4
                : 210-218
                Affiliations
                [1 ]Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China
                [2 ]Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
                Author notes
                [a]

                ORCID: 0000-0002-9322-5684.

                [b]

                ORCID: 0000-0001-5593-8563.

                [c]

                ORCID: 0000-0002-9509-2336.

                [d]

                ORCID: 0000-0002-3928-9660.

                [e]

                ORCID: 0000-0002-7257-0489.

                Article
                S1672-0229(15)00109-6
                10.1016/j.gpb.2015.09.001
                4610965
                26415621
                f84122e1-af8d-4e0e-b30c-936659303d55
                © 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 August 2015
                : 21 September 2015
                : 23 September 2015
                Categories
                Review

                systemic lupus erythematosus (sle),autoantibody profiling,proteomic microarray,biomarker,high-throughput assay

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