SP0075 Autoantibodies – not always what they seem. (12th June 2018)

• Record Type: Journal Article
• Authors: Meroni, P.L.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 20
• Page End: 20
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.7789
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Autoantibodies (autoAbs) are the most popular and used biomarkers for systemic rheumatic diseases (SRD). AutoAbs are becoming more and more important for: i) classification (including identification of disease subtypes), ii) diagnosis, iii) prognosis, iv) monitoring activity/organ-tissue damages as well as v) response to therapy. Moreover, autoAbs have been recently used as inclusion criteria in clinical trials and their presence is a formal requisite for prescribing some new drugs. The advent of new techniques, as well as the increasing number of autoimmune diagnostic laboratories, raise the issues of assay variability and reproducibility. In addition, the new techniques need to be validated versus the standard ones in order to determine and possibly improve the correct interpretation of their results. Harmonisation of the assays for autoAbs is becoming increasingly urgent and the availability of suitable reference material for calibration and quality control is emerging as a valuable tool for increasing assay reliability. Several international committees are joining their efforts in order to improve harmonisation and at the same time to avoid misdiagnosis, unnecessary repetition of tests and ultimately to optimise patient care and costs. On the other hand, the correct interpretation of the results depends on the technique used for detecting a given autoantibody and on its own characteristics (Meroni et al. Nat Rev Rheumato.l 10:35–43; 2014). The best example is the screening tests for antinuclear antibodies (ANA). Indirect immunofluorescence (IF) ANA testing has been suggested to be the golden standard technique for ANA screening by the American College Rheumatology task force in 2010 (Meroni and Schur Ann Rheum Dis . 69:1420–2; 2010). While the sensitivity of IF ANA is high, its specificity is low as well as its post-test probability. So, the strength of a positive ANA should be evaluated in the clinical context to avoid mistakes (Mahler et al J Immunl Res . 2014:315179 2014). In addition, the isolated ANA positivity with specific staining pattern (i.e. dense fine speckled 79 – DFS70) does not support the diagnosis of a SARD and should not be taken into consideration for both classification and inclusion criteria (Mahler et al. Autoimmun Rev. 15:198–01; 2016). IF offered advantages in comparison with the screening solid phase assays (SPA) available at the moment of the ACR position paper; however the improvement of the solid phase assays in the last years changed the situation in a substantial way. Advantages and disadvantages of the two techniques have been reviewed and discussed by several groups and none of the two tests appears to satisfy completely our needs. However, the combination of IF and SPA that include the main nuclear (cytoplasmic) antigens diagnostic for SARD, has been reported to display higher specificity and post-test probability than the use of the single tests (Bossuyt et la Ann Rheum Dis . 73:e10; 2014). New tests that employ a panel of autoantigens specific for a given subset of SARD (e.g. lupus-like, scleroderma, myositis, anti-phospholipid syndrome) are now available or are going to be launched soon increasing their specificity/post-test probability in a significant manner. For example, the combination of IF and SPA for ANA screening could decrease the risk of "false positive or negative" results, while the use of one screening assay and the new ANA profiles in the context of a specific clinical setting might increase the diagnostic power. In conclusion, our strategy to autoAb testing is changing and we should take advantage of the combination of the new serological tools for better understanding the meaning of a given positive result. The combination of the new tests will be pivotal for addressing the need for a Personalised Medicine in rheumatology. Disclosure of Interest: P. L. Meroni Speakers bureau: Pfizer, Abbvie, INOVA Diagnostics