Review Article | Published:

Standardization of autoantibody testing: a paradigm for serology in rheumatic diseases

Nature Reviews Rheumatology volume 10, pages 3543 (2014) | Download Citation

Abstract

Autoantibody measurement is an excellent tool to confirm the diagnosis of rheumatic autoimmune diseases. Hence, reliability and harmonization of autoantibody testing are essential, but these issues are still a matter of debate. Intrinsic variability in analytes and reagents as well as heterogeneity of the techniques are the main reasons for discrepancies in inter-laboratory variations and reporting of test results. This lack of reliability might be responsible for wrong or missed diagnoses, as well as additional costs due to assay repetition, unnecessary use of confirmatory tests and/or consequent diagnostic investigations. To overcome such issues, the standardization of autoantibody testing requires efforts on all aspects of the assays, including the definition of the analyte, the pre-analytical stages, the calibration method and the reporting of results. As part of such efforts, the availability of suitable reference materials for calibration and quality control would enable the development of a reliable reference system. Strong-positive sera from patients have been used as reference materials in most of the autoantibody assays for rheumatic diseases; however, antigen-affinity-purified immunoglobulin fractions or in some cases reliable monoclonal antibody preparations offer more adequate tools for standardization. Systematic assessments of reference materials are currently underway, and preliminary results appear to be encouraging.

Key points

  • Autoantibody measurement is required for the adequate diagnosis and management of systemic autoimmune rheumatic diseases

  • The advent of new techniques, as well as the increasing number of autoimmune diagnostic laboratories, raises the issues of assay variability and reproducibility

  • As a consequence, harmonization of the available assays is becoming increasingly urgent

  • The availability of suitable reference material for calibration and quality control is emerging as a valuable tool for increasing assay reliability

  • Initiatives for harmonization of testing have been started by several international committees and organizations

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Acknowledgements

Silvia S. Pierangeli suddenly passed away last August during the revision of the present Review. All the authors do not forget her enthusiasm and great contribution and would like to dedicate the present paper to her memory.

Author information

Affiliations

  1. Department of Clinical Sciences and Community Health, Division of Rheumatology, Istituto G. Pini, University of Milan, Piazza C. Ferrari 1, 20122 Milan, Italy.

    • Pier Luigi Meroni
    •  & Martina Biggioggero
  2. Divisions of Rheumatology and Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-0883, USA.

    • Silvia S. Pierangeli
  3. Protein Reference Unit, St George's Hospital, Blackshaw Road, London SW17 0NH, UK.

    • Joanna Sheldon
  4. European Commission Joint Research Centre, Institute for Reference Materials and Measurements (IRMM), Retieseweg 111, B-2440 Geel, Belgium.

    • Ingrid Zegers
  5. Istituto Auxologico Italiano, Experimental Laboratory of Immune-Rheumatology, Via G. Zucchi 18, 20095 Cusano Milanino, Milan, Italy.

    • Maria Orietta Borghi

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Contributions

All authors made substantial contributions to writing the manuscript and reviewing/editing it before submission. In addition, P. L. Meroni, M. Biggioggero, J. Sheldon, I. Zegers and M. O. Borghi researched data for the article, and P. L. Meroni, S. S. Pierangeli, J. Sheldon, I. Zegers and M. O. Borghi made substantial contributions to discussions of article content.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Pier Luigi Meroni.

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DOI

https://doi.org/10.1038/nrrheum.2013.180

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