The importance of determining antinuclear antibodies
DOI:
https://doi.org/10.13112/pc.1072Keywords:
ANTIBODIES, ANTINUCLEAR; CLINICAL LABORATORY TECHNIQUES; CONNECTIVE TISSUE DISEASES; ARTHRITIS, JUVENILEAbstract
Antinuclear antibodies are a large group of autoantibodies directed against various intracellular autoantigens and are primarily associated with systemic autoimmune diseases characterized by a specific autoantibody profile. Antinuclear antibodies are also an important factor in the diagnosis of juvenile idiopathic arthritis, autoimmune hepatitis 1, and primary biliary cholangitis.
Detection of antinuclear antibodies in serum facilitates the diagnosis of systemic autoimmune diseases and may be important in assessing disease activity, prognosis, and differential diagnosis.
The gold standard and the first-line test for the detection of antinuclear antibodies is indirect immunofluorescence using HEp-2 cells (human laryngeal epidermoid carcinoma cell line type 2) substrate, followed by detection of specific autoantibodies by confirmatory methods.
References
1. Sciascia S, Bizzaro N, Meroni PL, et al. Autoantibodies testing in autoimmunity: Diagnostic, prognostic and classification value. Autoimmun Rev. 2023;22:103356. doi:10.1016/j.autrev.2023.103356.
2. Agmon-Levin N, Damoiseaux J, Kallenberg C, 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. doi:10.1136/annrheumdis-2013-203863.
3. Chan EKL, Damoiseaux J, Carballo OG, et al. Report of the first international consensus on standardized nomenclature of antinuclear antibody HEp-2 cell patterns 2014–2015. Front Immunol. 2015;6:412. doi:10.3389/fimmu.2015.00412.
4. Bossuyt X, De Langhe E, Borghi MO, Meroni PL. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol. 2020;16:715-726. doi:10.1038/s41584-020-00523-z.
5. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145-172. doi:10.1016/j.jhep.2017.03.022.
6. Martini A, Ravelli A, Avcin T, et al. Toward new classification criteria for juvenile idiopathic arthritis: First steps, Pediatric Rheumatology International Trials Organization international consensus. J Rheumatol. 2019;46:190-197. doi:10.3899/jrheum.180168.
7. Meroni PL, Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis. 2010;69:1420-1422. doi:10.1136/ard.2009.127100.
8. Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res. 2014;2014:315179. doi:10.1155/2014/315179.
9. Andrade LEC, Klotz W, Herold M, et al. Reflecting on a decade of the international consensus on ANA patterns (ICAP): Accomplishments and challenges from the perspective of the 7th ICAP workshop. Autoimmun Rev. 2024;23:103608. doi:10.1016/j.autrev.2024.103608.
10. International consensus on ANA patterns (ICAP). 2021 [accessed 2025 January 10]. Available from: https://www.anapatterns.org/trees-2021.php
11. Bonroy C, Vercammen M, Fierz W, et al. Detection of antinuclear antibodies: Recommendations from EFLM, EASI and ICAP. Clin Chem Lab Med. 2023;61:1167-1198. doi:10.1515/cclm-2023-0456.
12. Andrade LEC, Damoiseaux J, Vergani D, Fritzler MJ. Antinuclear antibodies (ANA) as a criterion for classification and diagnosis of systemic autoimmune diseases. J Transl Autoimmun. 2022;5:100145. doi:10.1016/j.jtauto.2022.100145.
13. Storwick JA, Brett AC, Buhler K, et al. Prevalence and titres of antinuclear antibodies in juvenile idiopathic arthritis: A systematic review and meta-analysis. Autoimmun Rev. 2022;21:103086. doi:10.1016/j.autrev.2022.103086.
14. Aksu G, Gulez N, Azarsiz E, et al. Determination of cut-off titers and agreement between immunofluorescence and immunoblotting methods for detecting antinuclear antibodies in children. J Clin Lab Anal. 2010;24:230-236. doi:10.1002/jcla.20390.
15. Tešija Kuna A, Đerek L, Drvar V, et al. Assessment of antinuclear antibodies (ANA): National recommendations on behalf of the Croatian society of medical biochemistry and laboratory medicine. Biochem Med (Zagreb). 2021;31:020502. doi:10.11613/BM.2021.020502.
16. Hoffman IEA, Peene I, Veys EM, De Keyser F. Detection of specific antinuclear reactivities in patients with negative anti-nuclear antibody immunofluorescence screening tests. Clin Chem. 2002;48:2171–6. doi:10.1093/clinchem/48.12.2171
17. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725-34. doi:10.1002/art.1780400928
18. Tozzoli R, Bizzaro N, Tonutti E, 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. doi:10.1309/5N1M-595L-8X9Y-3X9F
19. Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med. 2000;124:71-81. doi:10.5858/2000-124-0071-GFCUOT
20. Pisetsky DS. Anti-DNA antibodies — quintessential biomarkers of SLE. Nat Rev Rheumatol. 2016;12:102-10. doi:10.1038/nrrheum.2015.151
21. Tonutti E, Bizzaro N, Morozzi G, et al. The ANA-reflex test as a model for improving clinical appropriateness in autoimmune diagnostics. Auto Immun Highlights. 2016;7:9. doi:10.1007/s13317-016-0080-0
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