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Review
. 2023 Aug;71(4):516-527.
doi: 10.1007/s12026-023-09362-8. Epub 2023 Jan 24.

Human antibody profiling technologies for autoimmune disease

Affiliations
Review

Human antibody profiling technologies for autoimmune disease

Lauren H Carlton et al. Immunol Res. 2023 Aug.

Abstract

Autoimmune diseases are caused by the break-down in self-tolerance mechanisms and can result in the generation of autoantibodies specific to human antigens. Human autoantigen profiling technologies such as solid surface arrays and display technologies are powerful high-throughput technologies utilised to discover and map novel autoantigens associated with disease. This review compares human autoantigen profiling technologies including the application of these approaches in chronic and post-infectious autoimmune disease. Each technology has advantages and limitations that should be considered when designing new projects to profile autoantibodies. Recent studies that have utilised these technologies across a range of diseases have highlighted marked heterogeneity in autoantibody specificity between individuals as a frequent feature. This individual heterogeneity suggests that epitope spreading maybe an important mechanism in the pathogenesis of autoimmune disease in general and likely contributes to inflammatory tissue damage and symptoms. Studies focused on identifying autoantibody biomarkers for diagnosis should use targeted data analysis to identify the rarer public epitopes and antigens, common between individuals. Thus, utilisation of human autoantigen profiling technology, combined with different analysis approaches, can illuminate both pathogenesis and biomarker discovery.

Keywords: Autoantigens; Autoimmune disease; Biomarker discovery; Epitope spreading; PhIP-Seq; Protein array.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart depicting the process of autoantigen discovery using human autoantigen profiling technologies. Autoimmune patient and healthy control sera are used in the autoantigen profiling technology in the Autoantigen Discovery phase. Complex bioinformatics is required, including targeted data analysis to filter for public epitopes and antigens for novel biomarker discovery. Detected antigens are then orthogonally validated on an immunoassay such as ELISA or Luminex bead-based assays with a larger sample cohort to confirm novel findings and inform new insights into disease pathogenesis. Figure created with Biorender.com

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