Skip to main content

Advertisement

SpringerLink
Log in

Autoimmune diagnostics: the technology, the strategy and the clinical governance

  • DIAGNOSTICS AND ENVIRONMENTAL FACTORS
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

In recent years, there has been a profound change in autoimmune diagnostics. From long, tiring and inaccurate manual methods, the art of diagnostics has turned to modern, rapid and automated technology. New antibody tests have been developed, and almost all autoimmune diseases now have some specific diagnostic markers. The current need to make the most of available economic and human resources has led to the production of diagnostic algorithms and guidelines designated for optimal strategic use of the tests and to increase the diagnostic appropriateness. An important role in this scenario was assumed by the laboratory autoimmunologist, whose task is not only to govern the analytical phase, but also to help clinicians in correctly choosing the most suitable test for each clinical situation and provide consultancy support. In this review, we summarize recent advances in technology, describe the diagnostic strategies and highlight the current role of the laboratory autoimmunologist in the clinical governance of autoimmune diagnostics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Nakamura RM, Bylund DJ. Factors influencing changes in the clinical immunology laboratory. Clin Chem. 1994;40:2193–204.

    CAS  PubMed  Google Scholar 

  2. Tozzoli R, Bizzaro N. The clinical autoimmunologist and the laboratory autoimmunologist: the two sides of the coin. Autoimmun Rev. 2012;11:766–70.

    Article  PubMed  Google Scholar 

  3. Tomar R. Total laboratory automation and diagnostic immunology. Clin Diagn Lab Immunol. 1999;6:293–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Bock JL. The new era of automated immunoassay. Am J Clin Pathol. 2000;113:628–46.

    Article  CAS  PubMed  Google Scholar 

  5. Wu AHB. A selected history and future of immunoassay development and applications in clinical chemistry. Clin Chim Acta. 2006;369:119–24.

    Article  CAS  PubMed  Google Scholar 

  6. Ekins RP. Ligand assays: from electrophoresis to miniaturized microarrays. Clin Chem. 1998;44:2015–30.

    CAS  PubMed  Google Scholar 

  7. Tozzoli R, Bonaguri C, Melegari A, Antico A, Bassetti D, Bizzaro N. Current state of diagnostic technologies in the autoimmunology laboratory. Clin Chem Lab Med. 2013;51:129–38.

    Article  CAS  PubMed  Google Scholar 

  8. Tozzoli R, Bizzaro N, Tonutti E, Villalta D, Bassetti D, Manoni F, et al. Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of autoimmune rheumatic diseases. Am J Clin Pathol. 2002;117:316–24.

    Article  PubMed  Google Scholar 

  9. Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis. 2010;69:1420–2.

    Article  CAS  PubMed  Google Scholar 

  10. Agmon-Levin N, Damoiseaux J, Kallenberg C, Sack U, Witte T, Herold M, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis. 2014;73:17–23.

    Article  CAS  PubMed  Google Scholar 

  11. Tozzoli R, Antico A, Porcelli B, Bassetti D. Automation in indirect immunofluorescence testing: a new step in the evolution of the autoimmunology laboratory. Autoimmun Highlights. 2012;3:59–65.

    Article  CAS  Google Scholar 

  12. Meroni PL, Bizzaro N, Cavazzana I, Borghi MO, Tincani A. Automated test of ANA immunofluorescence as throughput autoantibody detection technology: strengths and limitations. BMC Med. 2014;12:38.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Bizzaro N, Antico A, Platzgummer S, Tonutti E, Bassetti D, Pesente F, et al. Automated antinuclear immunofluorescence antibody screening: a comparative study of six computer-aided diagnostic systems. Autoimmun Rev. 2013;13:292–8.

    Article  PubMed  Google Scholar 

  14. Wang C, Wu J, Zong C, Xu J, Ju HX. Chemiluminescent immunoassay and its applications. Chin J Anal Chem. 2012;40:3–10.

    Article  Google Scholar 

  15. Tozzoli R, Villalta D. Autoantibody profiling of patients with antiphospholipid syndrome using an automated multiplexed immunoassay system. Autoimmun Rev. 2014;13:59–63.

    Article  CAS  PubMed  Google Scholar 

  16. Bizzaro N, Tozzoli R, Shoenfeld Y. Are we at a stage to predict autoimmune rheumatic diseases? Arthritis Rheum. 2007;56:1736–44.

    Article  CAS  PubMed  Google Scholar 

  17. Kostantinov KN, Tzamaloukas A, Rubin RL. Detection of autoantibodies in a point-of-care rheumatology setting. Autoimmun Highlights. 2013;4:55–61.

    Article  Google Scholar 

  18. Schünemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R, Vist GE, et al. GRADE: grading quality of evidence and strengths of recommendations for diagnostic tests and strategy. Br Med J. 2008;336:1106–10.

    Article  Google Scholar 

  19. Bizzaro N, Wiik A. Appropriateness in anti-nuclear antibody testing: from clinical request to strategic laboratory practice. Clin Exp Rheumatol. 2004;22:349–55.

    CAS  PubMed  Google Scholar 

  20. Solomon DH, Kavanaugh AJ, Schur PH, American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum. 2002;47:434–44.

    Article  PubMed  Google Scholar 

  21. Tampoia M, Brescia V, Fontana A, Zucano A, Morrone LF, Pansini N. Application of a combined protocol for rational request and utilization of antibody assays improves clinical diagnostic efficiency in autoimmune rheumatic disease. Arch Pathol Lab Med. 2007;131:112–6.

    CAS  PubMed  Google Scholar 

  22. Huizinga TW, Amos CI, van der Helm-van Mil AH, Chen W, van Gaalen FA, Jawaheer D, et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA–DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum. 2005;52:3433–8.

    Article  CAS  PubMed  Google Scholar 

  23. Irigoyen P, Lee AT, Wener MH, Li W, Kern M, Batliwalla F, et al. Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA–DR3 and the shared epitope alleles. Arthritis Rheum. 2005;52:3813–8.

    Article  CAS  PubMed  Google Scholar 

  24. Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GMC, van Veelen PA, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. PNAS. 2011;108:17372–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Lundberg K, Kinloch A, Fisher BA, Wegner N, Wait R, Charles P, et al. Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 2008;58:3009–19.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao J, Zhao Y, He J, Jia R, Li Z. Prevalence and significance of anti-peptidylarginine deiminase 4 antibodies in rheumatoid arthritis. J Rheumatol. 2008;35:969–74.

    CAS  PubMed  Google Scholar 

  27. Strollo R, Ponchel F, Malmström V, Rizzo P, Bombardieri M, Wenham CY, et al. Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis. Arthritis Rheum. 2013;65:1702–12.

    Article  CAS  PubMed  Google Scholar 

  28. Darrah E, Giles JT, Ols ML, Bull HG, Andrade F, Rosen A. Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity. Sci Transl Med. 2013;5:186ra65.

    PubMed Central  PubMed  Google Scholar 

  29. Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol. 1999;111:507–13.

    CAS  PubMed  Google Scholar 

  30. Savige J, Dimech W, Fritzler M, Goeken J, Hagen EC, Jennette JC, et al. Addendum to the international consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies. Am J Clin Pathol. 2003;120:312–8.

    Article  CAS  PubMed  Google Scholar 

  31. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.

    Article  CAS  PubMed  Google Scholar 

  32. Lakos G, Favaloro EJ, Harris EN, Meroni PL, Tincani A, Wong RC, Pierangeli SS. International consensus guidelines on anticardiolipin and anti-β2-glycoprotein I testing: report from the 13th international congress on antiphospholipid antibodies. Arthritis Rheum. 2012;64:1–10.

    Article  PubMed  Google Scholar 

  33. Pengo V, Banzato A, Denas G, Jose SP, Bison E, Hoxha A, Ruffatti A. Correct laboratory approach to APS diagnosis and monitoring. Autoimmun Rev. 2013;12:832–4.

    Article  CAS  PubMed  Google Scholar 

  34. Liu H, Norman GL, Shums Z, Worman HJ, Krawitt EL, Bizzaro N, et al. PBC screen: an IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J Autoimmun. 2010;35:436–42.

    Article  CAS  PubMed  Google Scholar 

  35. Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, et al. Overcoming a “probable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol. 2012;42:288–97.

    Article  CAS  PubMed  Google Scholar 

  36. Tonutti E, Visentini D, Picierno A, Bizzaro N, Villalta D, Tozzoli R, et al. Diagnostic efficacy of the ELISA test for the detection of deamidated anti-gliadin peptide antibodies in the diagnosis and monitoring of celiac disease. J Clin Lab Anal. 2009;23:165–71.

    Article  CAS  PubMed  Google Scholar 

  37. Tonutti E, Bizzaro N. Diagnosis and classification of celiac disease and gluten sensitivity. Autoimmun Rev. 2014;13:472–6.

    Article  CAS  PubMed  Google Scholar 

  38. Maglio M, Tosco A, Paparo F, Auricchio R, Granata V, Colicchio B, et al. Serum and intestinal celiac disease-associated antibodies in children with celiac disease younger than 2 years of age. J Pediatr Gastroenterol Nutr. 2010;50:43–8.

    Article  CAS  PubMed  Google Scholar 

  39. Volta U, Fabbri A, Parisi C. Deamidated gliadin peptide antibodies as a routine test for celiac disease: a prospective analysis. J Clin Gastroenterol. 2010;44:186–90.

    Article  PubMed  Google Scholar 

  40. Brusca I, Carroccio A, Tonutti E, Villalta D, Tozzoli R, Barrale M, et al. The old and new tests for celiac disease: which is the best test combination to diagnose celiac disease in pediatric patients? Clin Chem Lab Med. 2011;50:111–7.

    PubMed  Google Scholar 

  41. Bizzaro N, Tozzoli R, Villalta D, Fabris M, Tonutti E. Cutting-edge issues in celiac disease and in gluten intolerance. Clin Rev Allergy Immunol. 2012;42:279–87.

    Article  CAS  PubMed  Google Scholar 

  42. Villalta D, Alessio MG, Tampoia M, Tonutti E, Brusca I, Bagnasco M, et al. Diagnostic accuracy of IgA anti-tissue transglutaminase antibody assays in celiac disease patients with selective IgA deficiency. Ann N Y Acad Sci. 2007;1109:212–20.

    Article  CAS  PubMed  Google Scholar 

  43. Villalta D, Tonutti E, Prause C, Koletzko S, Uhlig HH, Vermeersch P, et al. IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency. Clin Chem. 2010;56:464–8.

    Article  CAS  PubMed  Google Scholar 

  44. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–60.

    Article  CAS  PubMed  Google Scholar 

  45. Department of Health. The new NHS: modern, dependable. London: Stationery Office; 1997.

    Google Scholar 

  46. Trenti T, Canali C, Scognamiglio A. Clinical governance and evidence-based laboratory medicine. Clin Chem Lab Med. 2006;44:724–32.

    Article  CAS  PubMed  Google Scholar 

  47. Lippi G. Governance of preanalytical variability: travelling the right path to the bright side of the moon? Chim Clin Acta. 2009;404:32–6.

    Article  CAS  Google Scholar 

  48. Wiik AS. Appropriateness of autoantibody testing in clinical medicine. Clin Chim Acta. 2003;333:177–80.

    Article  CAS  PubMed  Google Scholar 

  49. Wiik AS, Bizzaro N. Missing links in high quality diagnostics of inflammatory systemic rheumatic diseases. Autoimmun Highlights. 2012;3:35–49.

    Article  CAS  Google Scholar 

  50. Wiik AS, Gordon TP, Kavanaugh AF, Lahita RG, Reeves W, van Venrooij WJ, et al. Cutting edge diagnostics in rheumatology: the role of patients, clinicians, and laboratory scientists in optimizing the use of autoimmune serology. Arthritis Rheum. 2004;51:291–8.

    Article  PubMed  Google Scholar 

  51. Srivastava R, Bartlett WA, Kennedy IM, Hiney A, Fletcher C, Murphy MJ. Reflex and reflective testing: efficiency and effectiveness of adding on laboratory tests. Ann Clin Biochem. 2010;47:223–7.

    Article  CAS  PubMed  Google Scholar 

  52. Stinton LM, Fritzler MJ. A Clinical approach to autoantibody testing in systemic autoimmune rheumatic disorders. Autoimmun Rev. 2007;7:77–84.

    Article  CAS  PubMed  Google Scholar 

  53. Sciacovelli L, Secchiero S, Zardo L, Zaninotto M, Plebani M. External quality assessment: an effective tool for clinical governance in laboratory medicine. Clin Chem Lab Med. 2006;44:740–9.

    Article  CAS  PubMed  Google Scholar 

  54. Plebani M. Harmonization in laboratory medicine: the complete picture. Clin Chem Lab Med. 2013;51:741–5.

    CAS  PubMed  Google Scholar 

  55. Kairisto V, Hanninen KP, Leino A, Pulkki K, Peltola O, Nanto V, et al. Generation of reference values for cardiac enzymes from hospital admission laboratory data. Eur J Clin Chem Clin Biochem. 1994;32:789–96.

    CAS  PubMed  Google Scholar 

  56. Tozzoli R, Giavarina D, Villalta D, Soffiati G, Bizzaro N. Definition of reference limits for autoantibodies to thyroid peroxidase and thyroglobulin in a large population of outpatients using an indirect method based on current data. Arch Pathol Lab Med. 2008;132:1924–8.

    PubMed  Google Scholar 

  57. Bossuyt X. Clinical performance characteristics of a laboratory test. A practical approach in the autoimmune laboratory. Autoimmun Rev. 2009;8:543–8.

    Article  CAS  PubMed  Google Scholar 

  58. Bizzaro N, Morozzi G. A proposed model for effective collaboration between rheumatologists and clinical pathologists for the diagnosis of autoimmune rheumatic diseases. Rheumatol Int. 2009;29:849–51.

    Article  PubMed  Google Scholar 

  59. Barth JH. The role of clinical audit. In: Price CP, Christenson RH, editors. Evidence-based laboratory medicine. Washington, DC: AACC Press; 2003. p. 209–24.

    Google Scholar 

  60. Fritzler MJ. Toward a new autoantibody diagnostic orthodoxy: understanding the bad, good and indifferent. Autoimmun Highlights. 2012;3:51–8.

    Article  CAS  Google Scholar 

  61. Plebani M. Appropriateness in program for continuous quality improvement in clinical laboratories. Clin Chim Acta. 2003;333:131–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio di Patologia Clinica, Ospedale San Antonio, Via Morgagni, 18, 33028, Tolmezzo, UD, Italy

    Nicola Bizzaro

  2. Laboratorio di Patologia Clinica, A.O. S. Maria degli Angeli, Pordenone, Italy

    Renato Tozzoli

  3. Allergologia e Immunologia Clinica, A.O. S. Maria degli Angeli, Pordenone, Italy

    Danilo Villalta

Authors
  1. Nicola Bizzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renato Tozzoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danilo Villalta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicola Bizzaro.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bizzaro, N., Tozzoli, R. & Villalta, D. Autoimmune diagnostics: the technology, the strategy and the clinical governance. Immunol Res 61, 126–134 (2015). https://doi.org/10.1007/s12026-014-8587-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-014-8587-z

Keywords

Search

Navigation