Lúpus eritematoso sistêmico com fator antinuclear (FAN) negativo: um desafio no diagnóstico
DOI:
https://doi.org/10.34119/bjhrv6n1-089Keywords:
lúpus eritematoso sistêmico, anticorpos antinucleares, diagnósticoAbstract
O lúpus eritematoso sistêmico (LES) é uma doença auto-imune que afeta 20 a 150 pessoas por 100.000 habitantes, caracterizada pela produção de auto-anticorpos, sendo os principais anticorpos envolvidos na patofisiologia desta doença os anticorpos antinucleares conhecidos como fator antinúcleo (FAN). O FAN positivo é agora considerado o critério de entrada para a classificação dos pacientes com FAN negativo, o que representa um desafio diagnóstico para aqueles com FAN negativo, uma entidade clínica descrita desde 1976 com uma prevalência de 2-20%. Apesar dos avanços nas técnicas de identificação do FAN, há vários fatores do paciente como idade, atividade da doença, uso de glicocorticóides, proteinúria, infecção e/ou sepse, que levam à negatividade de anticorpos no diagnóstico; assim como diferentes fatores técnicos ao processar o FAN por imunofluorescência indireta (IFI). Esta revisão aborda critérios de classificação do LES, técnicas de identificação do FAN, causas de negatividade e outros métodos de diagnóstico para aqueles pacientes com anticorpos antinucleares negativo e LES clínico, com o objetivo de fornecer informações aos profissionais de saúde que permitam o diagnóstico e tratamento oportuno dos pacientes com esta patologia, melhorando assim seu prognóstico e qualidade de vida.
References
Manson JJ, Isenberg DA. The pathogenesis of systemic lupus erythematosus. Neth J Med. 2003;61(11):343-6.
Calderón JMS, Rivera CMM, Rivera DMM, Idrovo CAI. Lupus eritematoso sistémico, manifestaciones clínicas, diagnóstico y tratamiento. Anatomía Digit. 2021;4(1):244-61.
Kariburyo F, Xie L, Sah J, Li N, Lofland JH. Real-world medication use and economic outcomes in incident systemic lupus erythematosus patients in the United States. J Med Econ. 2020;23(1):1-9.
Kunz M. Lupus erythematosus. Part I: epidemiology, genetics and immunology. JDDG J Dtsch Dermatol Ges. 2013;11(8):709-20.
Scolnik M. Epidemiology of Lupus in Latin America. 2016;1(2):3.
Bossuyt X, De Langhe E, Borghi MO, Meroni PL. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol. 2020;16(12):715-26.
Soares C, Viana K, Moraes-Santos F, Vieira C, Lamarão F, Iglesias-Rodriguez M. PSY17 - Mortality Rate and Premature Mortality Due to Systemic Erythematosus Lupus (Sle) in Latin America, Us and England and Wales. Value Health. 2015;18(7):805-881.
Pons-Estel BA, Bonfa E, Soriano ER, Cardiel MH, Izcovich A, Popoff F, et al. First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR). Ann Rheum Dis. 2018;77(11):1549-57.
Jiang M, Near AM, Desta B, Wang X, Hammond ER. Disease and economic burden increase with systemic lupus erythematosus severity 1 year before and after diagnosis: a real-world cohort study, United States, 2004–2015. Lupus Sci Med. 2021;8(1):e000503.
Fortuna G, Brennan MT. Systemic Lupus Erythematosus: Epidemiology, Pathophysiology, Manifestations, and Management. Dent Clin North Am. 2013;57(4):631-55.
Gergianaki I, Bortoluzzi A, Bertsias G. Update on the epidemiology, risk factors, and disease outcomes of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2018;32(2):188-205.
Ugarte-Gil MF, González LA, Alarcón GS. Lupus: the new epidemic. Lupus. 2019;28(9):1031-50.
Petri M, Magder L. Classification criteria for systemic lupus erythematosus: a review. Lupus. 2004;13(11):829-37.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271-7.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and Validation of Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheum. 2012;64(8):2677-86.
Oku K, Atsumi T. Systemic lupus erythematosus: nothing stale her infinite variety. Mod Rheumatol. 2018;28(5):758-65.
Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151-9.
Kiriakidou M, Ching CL. Systemic Lupus Erythematosus. Ann Intern Med. 2020;172(11):81-96.
Hartman EAR, van Royen-Kerkhof A, Jacobs JWG, Welsing PMJ, Fritsch-Stork RDE. Performance of the 2012 Systemic Lupus International Collaborating Clinics classification criteria versus the 1997 American College of Rheumatology classification criteria in adult and juvenile systemic lupus erythematosus. A systematic review and meta-analysis. Autoimmun Rev. 2018;17(3):316-22.
Selvananda S, Kan SL. Performance of the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus in a multiethnic Malaysian cohort. Int J Rheum Dis. 2022;25(2):131-9.
Cheng S, Ding H, Xue H, Cao L. Evaluation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in children and adults. Clin Rheumatol. 2022;41(10):2995-3003.
Guavita-Navarro D, Gallego-Cardona L, Arredondo AM, Cubides H, Cajamarca-Barón J, Ibáñez C, et al. Comparison of the sensitivity of the EULAR / ACR 2019 and SLICC 2012 classification criteria in a Colombian population with systemic lupus erythematosus. J Transl Autoimmun. 2021;4.
Kumar Y, Bhatia A, Minz RW. Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited. Diagn Pathol. 2009;4 (1).
Leuchten N, Hoyer A, Brinks R, Schoels M, Schneider M, Smolen J, et al. Performance of Antinuclear Antibodies for Classifying Systemic Lupus Erythematosus: A Systematic Literature Review and Meta-Regression of Diagnostic Data. Arthritis Care Res. 2018;70(3):428-38.
Choi MY, Clarke AE, St Pierre Y, Hanly JG, Urowitz MB, Romero-Diaz J, et al. Antinuclear Antibody-Negative Systemic Lupus Erythematosus in an International Inception Cohort. Arthritis Care Res. 2019;71(7):893-902.
Novak S. Clinical significance of antinuclear antibodies and other serological abnormalities in systemic lupus erythematosus (SLE). Reumatizam. 2009;56(2):22-5.
Pisetsky DS. Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification. Scand J Immunol. 2012;76(3):223-8.
Perez D, Gilburd B, Cabrera-Marante O, Martinez-Flores JA, Serrano M, Naranjo L, et al. Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies. Clin Chem Lab Med. 2018;56(10):1771-7.
Pisetsky DS, Lipsky PE. New insights into the role of antinuclear antibodies in systemic lupus erythematosus. Nat Rev Rheumatol. 2020;16(10):565-79.
Callado MRM, Barroso MN de A, Alves VM, Abreu MA de L, Muniz LMMM, Lima JRC. Antinuclear antibodies: two-step detection strategy. Immunol Invest. 2014;43(1):86-95.
Pisetsky DS, Bossuyt X, Meroni PL. ANA as an entry criterion for the classification of SLE. Autoimmun Rev. 2019;18(12):102400.
Li H, Zheng Y, Chen L, Lin S. High titers of antinuclear antibody and the presence of multiple autoantibodies are highly suggestive of systemic lupus erythematosus. Sci Rep. 2022;12(1).
Vasdev V, Patnaik SK, Bhakuni DS, Shanmuganandan K, Bhayana A, Mullick G, et al. Assessment of ideal serum dilution for screening of antinuclear antibodies by an indirect immunofluorescence method in diagnosis of autoimmune disorders. Med J Armed Forces India. 2022;78(1):54-60.
Choi MY, Clarke AE, Urowitz M, Hanly J, St-Pierre Y, Gordon C, et al. Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann Rheum Dis. 2022;81(8):1143-50.
Silva MJ, Dellavance A, Baldo DC, Rodrigues SH, Grecco M, Prado MS, et al. Interkit Reproducibility of the Indirect Immunofluorescence Assay on HEp-2 Cells Depends on the Immunofluorescence Reactivity Intensity and Pattern. Front Immunol. 2022;12.
Naides SJ, Genzen JR, Abel G, Bashleben C, Ansari MQ. Antinuclear Antibodies Testing Method Variability: A Survey of Participants in the College of American Pathologists’ Proficiency Testing Program. J Rheumatol. 2020;47(12):1768-73.
Yuan W, Cao H, Li W, Wu X, Zheng J. Comparison study of bead-based and line-blot multiplex ANA immunoassays in the diagnosis of systemic autoimmune rheumatic diseases. Clin Rheumatol. 2022;41(3):899-909.
Orme ME, Andalucia C, Sjölander S, Bossuyt X. A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases. Clin Chem Lab Med. 2021;59(3):547-61.
Song LJ, Ding F, Liu HX, Shu Q, Yu X, Li J, et al. Analysis of 15 patients with systemic lupus erythematosus manifesting with negative immunofluorescence anti-nuclear antibodies after treatment. 2012;21(8):919-24.
Pisetsky DS, Spencer DM, Lipsky PE, Rovin BH. Assay variation in the detection of antinuclear antibodies in the sera of patients with established SLE. Ann Rheum Dis. 2018;77(6):911-3.
Copple SS, Giles SR, Jaskowski TD, Gardiner AE, Wilson AM, Hill HR. Screening for IgG antinuclear autoantibodies by HEp-2 indirect fluorescent antibody assays and the need for standardization. Am J Clin Pathol. 2012;137(5):825-30.
Alexander RV, Rey DS, Conklin J, Domingues V, Ahmed M, Qureshi J, et al. A multianalyte assay panel with cell-bound complement activation products demonstrates clinical utility in systemic lupus erythematosus. Lupus Sci Med. 2021;8(1).
Jiang Z, Shao M, Dai X, Pan Z, Liu D. Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning. Front Genet. 2022;13.
Awang Kechik FNA, Abdullah M, Arip M, Hassan M, Mahayidin H. Clinical usefulness of anti-cell membrane DNA autoantibodies in serology negative systemic lupus erythematosus. Malays J Pathol. 2022;44(1):75-81.
