Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Technology Insight: can autoantibody profiling improve clinical practice?

Abstract

A hallmark of autoimmune diseases is the production of high titers of highly specific autoantibodies, which are routinely measured to guide clinical decision-making. Multiplex antigen microarrays are powerful tools that can provide profiles of the autoantibodies found in blood and other biological fluids. This high-throughput technology allows for rapid identification of antibody and antigen biomarker sets, which is sorely needed in the clinic to improve diagnosis, predictions of prognosis, and selection of targeted therapies. In this article we will describe the antigen microarray technologies that are currently available, and those that are in development. We highlight recent applications for antibody profiling, as well as the challenges that need to be faced before such technologies enter the clinic.

Key Points

  • Antigen arrays are available for rapid detection of multiple autoantibodies in microliter volumes of biological fluids

  • Multiplex antigen arrays are invaluable tools for identifying disease-specific autoantibody signatures

  • Autoantibody profiles can be followed over time as markers of disease remission or relapse

  • Novel antigens can be identified by testing reactivity of autoimmune sera to candidate antigens

  • Antigen-array technologies and the tools necessary for data interpretation are developing at an unprecedented rate

  • Individual autoantibody signatures can form the basis for patient-specific therapies

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A schematic diagram that illustrates the steps involved in content generation, processing and data analysis for antigen microarrays.
Figure 2: Protein microarray for connective tissue diseases.

Similar content being viewed by others

References

  1. von Mühlen CA and Tan EM (1995) Autoantibodies in the diagnosis of systemic rheumatic diseases. Semin Arthritis Rheum 24: 323–358

    Article  Google Scholar 

  2. Anderson AC et al. (2000) High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: mechanisms of selection of the self-reactive repertoire. J Exp Med 191: 761–770

    Article  CAS  Google Scholar 

  3. Altman JD et al. (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94–96

    Article  CAS  Google Scholar 

  4. Steinman L (1996) A few autoreactive cells in an autoimmune infiltrate control a vast population of nonspecific cells: a tale of smart bombs and the infantry. Proc Natl Acad Sci USA 93: 2253–2256

    Article  CAS  Google Scholar 

  5. Graham KL et al. (2004) High-throughput methods for measuring autoantibodies in systemic lupus erythematosus and other autoimmune diseases. Autoimmunity 37: 269–272

    Article  CAS  Google Scholar 

  6. Schena M et al. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467–470

    Article  CAS  Google Scholar 

  7. Mattoon D et al. (2005) Biomarker discovery using protein microarray technology platforms: antibody–antigen complex profiling. Expert Rev Proteomics 2: 879–889

    Article  CAS  Google Scholar 

  8. Kersten B et al. (2005) Multiplex approaches in protein microarray technology. Expert Rev Proteomics 2: 499–510

    Article  CAS  Google Scholar 

  9. Robinson WH et al. (2002) Autoantigen microarrays for multiplex characterization of autoantibody responses. Nat Med 8: 295–301

    Article  CAS  Google Scholar 

  10. Hueber W et al. (2005) Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis Rheum 52: 2645–2655

    Article  CAS  Google Scholar 

  11. Zhen QL et al. (2005) Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays. J Clin Invest 115: 3428–3349

    Article  CAS  Google Scholar 

  12. Lueking A et al. (2005) Profiling of alopecia areata autoantigens based on protein microarray technology. Mol Cell Proteomics 4: 1382–1390

    Article  CAS  Google Scholar 

  13. Robinson WH et al. (2003) Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat Biotechnol 21: 1033–1039

    Article  CAS  Google Scholar 

  14. Kanter JL et al. (2006) Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 12: 138–143

    Article  CAS  Google Scholar 

  15. Quintana FJ et al. (2004) Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes. Proc Natl Acad Sci USA 101 (Suppl 2): 14615–14621

    Article  CAS  Google Scholar 

  16. Hiller R et al. (2002) Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 16: 414–416

    Article  CAS  Google Scholar 

  17. Wiltshire S et al. (2000) Detection of multiple allergen-specific IgEs on microarrays by immunoassay with rolling circle amplification. Clin Chem 46: 1990–1993

    CAS  PubMed  Google Scholar 

  18. Tong M et al. (2005) A multiplexed and miniaturized serological tuberculosis assay identifies antigens that discriminate maximally between TB and non-TB sera. J Immunol Methods 301: 154–163

    Article  CAS  Google Scholar 

  19. Neuman de Vegvar HE et al. (2003) Microarray profiling of antibody responses against simian–human immunodeficiency virus: postchallenge convergence of reactivities independent of host histocompatibility type and vaccine regimen. J Virol 77: 11125–11138

    Article  CAS  Google Scholar 

  20. Steller S et al. (2005) Bacterial protein microarrays for identification of new potential diagnostic markers for Neisseria meningitidis infections. Proteomics 5: 2048–2055

    Article  CAS  Google Scholar 

  21. Thirumalapura NR et al. (2005) Lipopolysaccharide microarrays for the detection of antibodies. J Immunol Methods 298: 73–81

    Article  CAS  Google Scholar 

  22. Davies DH et al. (2005) Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci USA 102: 547–552

    Article  CAS  Google Scholar 

  23. Li B et al. (2005) Protein microarray for profiling antibody responses to Yersinia pestis live vaccine. Infect Immun 73: 3734–3739

    Article  CAS  Google Scholar 

  24. Davies DH et al. (2005) Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice. J Virol 79: 11724–11733

    Article  CAS  Google Scholar 

  25. Wang D et al. (2002) Carbohydrate microarrays for the recognition of cross-reactive molecular markers of microbes and host cells. Nat Biotechnol 20: 275–281

    Article  CAS  Google Scholar 

  26. Lawrie CH et al. (2006) Cancer-associated carbohydrate identification in Hodgkin's lymphoma by carbohydrate array profiling. Int J Cancer 118: 3161–3166

    Article  CAS  Google Scholar 

  27. Chatterjee M et al. (2006) Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. Cancer Res 66: 1181–1190

    Article  CAS  Google Scholar 

  28. Joos TO et al. (2000) A microarray enzyme-linked immunosorbent assay for autoimmune diagnostics. Electrophoresis 21: 2641–2650

    Article  CAS  Google Scholar 

  29. Horn S et al. (2006) Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease-associated protein chip. Proteomics 6: 605–613

    Article  CAS  Google Scholar 

  30. Subramanian S et al. (2006) A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci USA 103: 9970–9975

    Article  CAS  Google Scholar 

  31. Kattah MG et al. (2006) A new two-color Fab labeling method for autoantigen protein microarrays. Nat Methods 3: 745–751

    Article  CAS  Google Scholar 

  32. Sekine H et al. (2006) Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus. J Immunol 177: 7423–7434

    Article  CAS  Google Scholar 

  33. Arbuckle MR et al. (1999) Shared early autoantibody recognition events in the development of anti-Sm B/B' in human lupus. Scand J Immunol 50: 447–455

    Article  CAS  Google Scholar 

  34. Li N et al. (2003) The role of intramolecular epitope spreading in the pathogenesis of endemic pemphigus foliaceus (fogo selvagem). J Exp Med 197: 1501–1510

    Article  CAS  Google Scholar 

  35. Nimmerjahn F and Ravetch JV (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310: 1510–1512

    Article  CAS  Google Scholar 

  36. Graham KL et al. (2006) Autoantigen arrays for multiplex analysis of antibody isotypes. Proteomics 6: 5720–5724

    Article  CAS  Google Scholar 

  37. Fontoura P et al. (2005) Antigen-specific therapies in multiple sclerosis: going beyond proteins and peptides. Int Rev Immunol 24: 415–446

    Article  CAS  Google Scholar 

  38. Albani S and Prakken B (2006) T cell epitope-specific immune therapy for rheumatic diseases. Arthritis Rheum 54: 19–25

    Article  CAS  Google Scholar 

  39. Fathman CG et al. (2005) An array of possibilities for the study of autoimmunity. Nature 435: 605–611

    Article  CAS  Google Scholar 

  40. Uchida T et al. (2002) Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. J Proteome Res 1: 495–499

    Article  CAS  Google Scholar 

  41. Robinson WH (2006) Antigen arrays for antibody profiling. Curr Opin Chem Biol 10: 67–72

    Article  CAS  Google Scholar 

  42. Fritzler MJ (2006) Advances and applications of multiplexed diagnostic technologies in autoimmune diseases. Lupus 15: 422–427

    Article  CAS  Google Scholar 

  43. Angenendt P (2005) Progress in protein and antibody microarray technology. Drug Discov Today 10: 503–511

    Article  CAS  Google Scholar 

  44. Guilleaume B et al. (2005) Systematic comparison of surface coatings for protein microarrays. Proteomics 5: 4705–4712

    Article  CAS  Google Scholar 

  45. Binder SR (2006) Autoantibody detection using multiplex technologies. Lupus 15: 412–421

    Article  CAS  Google Scholar 

  46. Balboni I et al. (2006) Multiplexed protein array platforms for analysis of autoimmune diseases. Annu Rev Immunol 24: 391–418

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank members of the laboratories of PJ Utz, William H Robinson and Larry Steinman for the development of some of the technologies described in this article. V Sharp was funded by an NIH grant. PJ Utz is the recipient of a Donald E and Delia B Baxter Foundation Career Development Award, and was supported by the Dana Foundation, the Floren Family Trust, the Northern California Chapter of the Arthritis Foundation, NIH grants, and a proteomics contract from the National Heart, Lung, and Blood Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Veronika Sharp.

Ethics declarations

Competing interests

PJ Utz states the following conflict of interest disclosures: that in the past 3 years he has served as a consultant at Centocor (Horsham, PA), Biogen Idec (Cambridge, MA), and Genentech, Inc (South San Francisco, CA), and Avanir, Inc (La Jolla, CA); he is a member of the Scientific Advisory Board of Monogram Biosciences (South San Francisco, CA) and XDx, Inc (South San Francisco, CA), and is a co-founder of and consultant to Bayhill Therapeutics (Palo Alto, CA).

V Sharp declared no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharp, V., Utz, P. Technology Insight: can autoantibody profiling improve clinical practice?. Nat Rev Rheumatol 3, 96–103 (2007). https://doi.org/10.1038/ncprheum0404

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0404

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing