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

Journal name:
Nature Reviews Rheumatology
Year published:
Published online


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.


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Author information


  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


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.

Competing interests statement

The authors declare no competing interests.

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Author details

  • Pier Luigi Meroni

    Pier Luigi Meroni is a Professor of Rheumatology at the University of Milan, Italy, and head of the Division of Rheumatology of the Department of Clinical Sciences and Community Health. His clinical and scientific work focuses on autoimmune and rheumatic diseases, particularly on the pathogenic role of serum autoantibodies. He has organized and chaired several international meetings on autoimmunity, published widely, and in 1997 received the Roussel Prize (Rome) for studies on age-associated immune-deficiencies, and in 2005 the EULAR Prize (Vienna) for research on the infectious aetiology of antiphospholipid syndrome.

  • Martina Biggioggero

    Martina Biggioggero is Specialist Registrar in Rheumatology and assistant Researcher at the Department of Clinical Sciences and Community Health, University of Milan, Italy. Her clinical main interests include connective tissue diseases and pregnancy in rheumatic conditions.

  • Silvia S. Pierangeli

    Silvia S. Pierangeli was Professor of Medicine, Microbiology and Pathology, and Director of a research and clinical laboratory at the University of Texas Medical branch, Galveston, TX, USA. She has been a leader on diagnostic and pathogenic aspects of APS. Her laboratory is certified by the College of American Pathologists as a reference centre for antiphospholipid antibodies.

  • Joanna Sheldon

    Joanna Sheldon is Director of the Supraregional Protein Reference Unit at St George's Hospital, London, UK. Her work is focused on defining the highest standards of laboratory testing for analyses used in the diagnosis and management of patients with immunological diseases.

  • Ingrid Zegers

    Ingrid Zegers is a biochemist responsible for the development of reference materials for clinical measurements at the European Commission Joint Research Centre, Institute for Reference Materials and Measurements (IRMM), IRMM has produced reference materials for proteins such as albumin, C reactive protein and cystatin C.

  • Maria Orietta Borghi

    Maria Orietta Borghi, BS, PhD, is Deputy Director of the Experimental Laboratory of Immuno-Rheumatology and is in charge of the Cytometry Laboratory at the Istituto Auxologico Italiano. Her main research interests include autoantibody characterization and pathogenic mechanisms involved in systemic and organ-specific autoimmune diseases.

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