2018, Number 4
<< Back Next >>
Rev cubana med 2018; 57 (4)
Optimization of the diagnostic algorithm of antinuclear antibodies
Kokuina E, González YF, Marrero-Hernandez D, Peńa CY, Estévez TM
Language: Spanish
References: 25
Page: 1-14
PDF size: 313.23 Kb.
ABSTRACT
Introduction: The antinuclear antibody test is a powerful tool for diagnosing rheumatic diseases. Antinuclear antibodies are determined in the laboratory by an algorithm or sequence that starts with a screening test and continues with the identification of the most common antinuclear specificities. But how to interpret the discordant results between the two levels of study of antinuclear antibodies?
Objective: To determine the less frequent antinuclear specificities in positive patients of ANA screening and negative of the most common specificities.
Methods: A prospective study was done on 88 consecutive patients referred for the routine ANA screening with a positive result of screening by enzyme-linked immunosorbent assay (ELISA) but negative for anti-double-stranded DNA (dc, IgG) and common extractable anti-nuclear antigens (ENAc). The corresponding serum samples were evaluated by indirect immunofluorescence on human laryngeal epidermoid carcinoma cells (IFI-HEp-2) and by ELISA for the individual detection of specific ANA.
Results: The ANA test by IFI / HEp-2 was positive in 56/88 (63.6 %) and the antinuclear specificities were detected in 57/88 (64.8 %) samples, in decreasing Anti-Nucs order: 16/88 (18.2 %); anti-centromere (CENP-B): 15/88 (17.0 %); -histona: 15/88 (17 %); -PM/Scl: 13/88 (14.8 %); -ADNsc: 11/88 (12.5 %) and -ENAc individual: 8/88 (9.1 %). The sensitivity of IFI-HEp-2 for antinuclear specificities was 0.83 (95 % CI: 0.72-0.93). No history of rheumatic disease associated with ANA was read in (26/31) 83.9 % patients with negative subserology.
Conclusions: The majority of patients with discordant results between the first and second level of ANA were positive of less common antinuclear specificities, but of recognized diagnostic value.
REFERENCES
Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA, American College of Pathologists. 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.
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.
Mahler M, Fritzler MJ. Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci. 2010;1183:267-87.
Ho CH, Chauhan K. Lupus Erythematosus, Drug-Induced. StatPearls. Treasure Island (FL): StatPearls Publishing; 2017.
Tonuttia E, Bassetti D, Piazza A, Visentini D, Poletto M, Bassetto F, et al. Diagnostic accuracy of ELISA methods as an alternative screening test to indirect immunofluorescence for the detection of antinuclear antibodies: evaluation of five commercial kits. Autoimmunity. 2004;37:171-6.
Fenger M, Wiik A, Hřier-Madsen M, Lykkegaard JJ, Rozenfeld T, Hansen MS, et al. Detection of antinuclear antibodies by solid-phase immunoassays and immunofluorescence analysis. Clin Chem. 2004;50:2141-7.
de Almeida Brito F, Maria Elói Santos S, Aparecida Ferreira G, Pedrosa W, Gradisse J, Cristina Costa L, et al. Diagnostic evaluation of ELISA and chemiluminescent assays as alternative screening tests to indirect immunofluorescence for the detection of antibodies to cellular antigens. Am J Clin Pathology. 2016 [acceso: 04/12/2018];145:323-31. Disponible en: https://doi.org/10.1093/ajcp/aqv083
Bizzaro N, Villalta D, Giavarina D, Tozzoli R. Are anti-nucleosome antibodies a better diagnostic marker than anti-dsDNA antibodies for systemic lupus erythematosus? A systematic review and a study of metanalysis. Autoimmun Rev. 2012;12:97-106.
Van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2734-47.
Koenig M, Dieude M, Senecal JL. Predictive value of antinuclear autoantibodies: the lessons of the systemic sclerosis autoantibodies. Autoimmun Rev. 2008;7:588-93.
Coghlan JG, Denton CP, Grünig E, Bonderman D, Distler O, Khanna D, et al. DETECT study group: Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73:1340-9.
Vasoo S. Drug-induced lupus: an update. Lupus. 2006;15:757-61.
Niklas K, Niklas AA, Majewski D, Puszczewicz M. Rheumatic diseases induced by drugs and environmental factors the state of the art part one. Reumatologia. 2016;54(3):122-7.
Sui M, Lin Q, Xu Z, Han X, Xie R, Jia X, et al. Simultaneous positivity for anti-DNA, anti-nucleosome and anti-histone antibodies is a marker for more severe lupus nephritis. J Clin Immunol. 2013;33:378-87.
Reimer G, Scheer U, Peters JM, Tan EM. Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/ /scleroderma overlap syndromes. J Immunol. 1986;137:3802-8.
Kuwana M. Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting. J Nippon Med Sch. 2017;84:56-63.
Ignat GP, Rat AC, Sychra JJ, Vo J, Varga J, Teodorescu M. Information on diagnosis and management of systemic lupus erythematosus derived from the routine measurement of 8 nuclear autoantibodies. J Rheumatol. 2003;30:1761-9.
M Pavlovic R, Chen A, M Kats. Highly specific novel method for isolation and purification of lupus anti-DNA antibody via oligo-(dT) magnetic beads. Ann NY Acad Sci. 2007;1108:203-17.
Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test. Am J Med. 2013;126:342-8.
Myckatyn SO, Russell AS. Outcome of positive anti-nuclear antibodies in individuals without connective tissue disease. J Rheumatol. 2003;30:736-9.
Fritzler MJ. Autoantibody assays: performance, interpretation, and standardization. En: Rose NR, Mackay IR. (Eds.), The Autoimmune Diseases, 5 ed. Elsevier Academic Press; 2014, p. 1161-75.
Satoh M, Chan EK, Ho LA, Rose KM, Parks CG, Cohn RD, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 2012;64:2319-27.
Guyomard S, Salles G, Coudurier M, Rousset H, Coiffier B, Bienvenu J, et al. Prevalence and pattern of antinuclear antibodies in 347 patients with non-Hodgkin’s lymphoma. Br J Haematol. 2003;123:90-9.
Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526-33.
Ma WT, Chang C, Gershwin ME, Lian ZX. Development of autoantibodies precedes clinical manifestations of autoimmune diseases: a comprehensive review. J Autoimmun. 2017;83:95-112.