Low-titer autoantibodies and overdiagnosis: impact on testing cascades.
DOI:
https://doi.org/10.70577/3j0hk355Keywords:
autoanticuerpos, baja titulación, sobrediagnóstico, cascadas diagnósticas, gobernanza diagnóstica, laboratorio clínico, sobreutilización, eficiencia diagnóstica.Abstract
The detection of low-titer autoantibodies in clinical practice represents an increasing challenge due to its association with overdiagnosis and the activation of diagnostic testing cascades that increase resource utilization, unnecessary medicalization, and prolonged care pathways without proportional clinical benefit. The objective of this study was to analyze the impact of low-titer autoantibodies on the generation of diagnostic cascades and to evaluate how modifications in interpretative thresholds and institutional governance of laboratory test demand influence confirmatory efficiency and the reduction of overutilization. The methodology followed a quantitative explanatory approach based on secondary data from governmental reports and national and international organizations, complemented by advanced statistical modeling using segmented time series regression and multilevel mixed-effects models to estimate institutional variability and the effect of structural interventions. The results showed that low titers account for the highest proportion of positive findings but exhibit limited confirmatory yield, whereas raising interpretative thresholds significantly reduces the volume of positives entering diagnostic pathways and improves predictive value. In addition, a substantial proportion of variability in cascade activation was attributable to organizational factors rather than clinical differences, particularly the absence of formal protocols, non-contextualized interpretation of results, and lack of repetition control. Overall, the findings indicate that low-titer positivity functions as a structural trigger of overutilization when not integrated with strict clinical criteria and institutional mechanisms regulating laboratory test demand.
Downloads
References
Akmatov, M. K., Röber, N., Ahrens, W., Flesch-Janys, D., Fricke, J., Greiser, H., et al. (2017). Anti-nuclear autoantibodies in the general German population: Prevalence and lack of association with selected cardiovascular and metabolic disorders. Arthritis Research & Therapy, 19(1), 127. https://doi.org/10.1186/s13075-017-1338-5 DOI: https://doi.org/10.1186/s13075-017-1338-5
Añel Rodríguez, R. M., Astier Peña, M. P., & Coll Benejam, T. (2023). ¿Por qué resulta cada vez más complicado “hacer lo que hay que hacer” y “dejar de hacer lo que no hay que hacer”? Estrategias para revertir las prácticas de bajo valor. Atención Primaria, 55(7), 102630. https://doi.org/10.1016/j.aprim.2023.102630 DOI: https://doi.org/10.1016/j.aprim.2023.102630
Aringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey-Goldman, R., et al. (2019). 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis & Rheumatology, 71(9), 1400–1412. https://doi.org/10.1002/art.40930 DOI: https://doi.org/10.1002/art.40930
Ballesteros Ugarte, E., & Trunzo, P. (2021). Prevención cuaternaria y prácticas de bajo valor. Salud, Ciencia y Tecnología, 1. https://doi.org/10.56294/saludcyt202127 DOI: https://doi.org/10.56294/saludcyt202127
Conrad, K., Röber, N., Andrade, L. E. C., & Mahler, M. (2017). The clinical relevance of anti-DFS70 autoantibodies. Clinical Reviews in Allergy & Immunology, 52(2), 202–216. https://doi.org/10.1007/s12016-016-8564-5 DOI: https://doi.org/10.1007/s12016-016-8564-5
Damoiseaux, J., Andrade, L. E. C., Carballo, O. G., Conrad, K., Francescantonio, P. L. C., Fritzler, M. J., et al. (2022). Clinical relevance of HEp-2 indirect immunofluorescent patterns: Updated perspectives for standardization and interpretation. Autoimmunity Reviews, 21(4), 103037. https://doi.org/10.1016/j.autrev.2022.103037 DOI: https://doi.org/10.1016/j.autrev.2022.103037
Dávila Muñoz, J. A., & Parrales Pincay, D. R. (2023). Indicadores de calidad y su relación con la gestión del laboratorio clínico. MQRInvestigar, 7(3), 2629–2647. https://doi.org/10.56048/mqr20225.7.3.2023.2629-2647 DOI: https://doi.org/10.56048/MQR20225.7.3.2023.528-542
Dinse, G. E., Parks, C. G., Weinberg, C. R., Co, C. A., Wilkerson, J., Zeldin, D. C., & Chan, E. K. L. (2020). Increasing prevalence of antinuclear antibodies in the United States. Arthritis & Rheumatology, 72(6), 1026–1035. https://doi.org/10.1002/art.41214 DOI: https://doi.org/10.1002/art.41214
García de la Torre, I. (2022). Interpretación clínica de anticuerpos antinucleares y decisiones de confirmación serológica en sospecha de autoinmunidad sistémica. Reumatología Clínica, 18(6), 361–368. https://doi.org/10.1016/j.reuma.2022.01.004 DOI: https://doi.org/10.1016/j.reuma.2022.01.004
Loor, A. R., & Uzcanga, S. A. (2023). Anticuerpos antinucleares: Distribución de patrones y titulaciones en un laboratorio clínico de referencia (Ecuador). QhaliKay, Revista de Ciencias de la Salud, 7(1), 6–14. https://doi.org/10.33936/qkrcs.v7i1.5470
López, L., Paredes, C., & Zambrano, J. (2023). Gestión de la calidad en el laboratorio clínico: Estándares, control interno y seguridad del paciente. RECIAMUC, 7(1), 145–160. https://doi.org/10.26820/reciamuc/7.(1).enero.2023.145-160
Mahler, M., Parker, T., Peebles, C. L., Andrade, L. E. C., Swart, A., Carbone, Y., et al. (2012). Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. The Journal of Rheumatology, 39(11), 2104–2110. https://doi.org/10.3899/jrheum.120598 DOI: https://doi.org/10.3899/jrheum.120598
Masetti, R., Tiri, A., Tignanelli, A., Turrini, E., Argentiero, A., & Pession, A. (2021). Autoimmunity and cancer. Autoimmunity Reviews, 20(9), 102882. https://doi.org/10.1016/j.autrev.2021.102882 DOI: https://doi.org/10.1016/j.autrev.2021.102882
Minué Lorenzo, S., Astier Peña, M. P., & Coll Benejam, T. (2021). El error diagnóstico y sobrediagnóstico en atención primaria. Propuestas para la mejora de la práctica clínica en medicina de familia. Atención Primaria, 53(Supl. 1), 102227. https://doi.org/10.1016/j.aprim.2021.102227 DOI: https://doi.org/10.1016/j.aprim.2021.102227
Pashnina, I. A., Krivolapova, I. M., Fedotkina, T. V., Ryabkova, V. A., Chereshneva, M. V., Churilov, L. P., & Chereshnev, V. A. (2021). Antinuclear autoantibodies in health: Autoimmunity is not a synonym of autoimmune disease. Antibodies, 10(1), 9. https://doi.org/10.3390/antib10010009 DOI: https://doi.org/10.3390/antib10010009
Pitta Villasboa, G. M., Frontanilla, T., Servián, L., Ortiz, X., Henning, R., & Ortiz Galeano, I. (2022). Prevalencia de anticuerpos antinucleares en médicos residentes aparentemente sanos del Hospital de Clínicas, San Lorenzo. Revista Virtual de la Sociedad Paraguaya de Medicina Interna, 9(1), 71–80. https://doi.org/10.18004/rvspmi/2312-3893/2022.09.01.71 DOI: https://doi.org/10.18004/rvspmi/2312-3893/2022.09.01.71
Rojas Armadillo, H., Pantoja Gómez, L. V., & Mendoza Arauz, R. (2022). La prevención cuaternaria y su impacto en el sobrediagnóstico. Atención Primaria Práctica, 4, 100137. https://doi.org/10.1016/j.appr.2022.100137 DOI: https://doi.org/10.1016/j.appr.2022.100137
Salinas, M., López, I., Llopis, M. A., Martínez, M., Llopis, F., & García, M. (2024). Demand management in laboratory medicine: Reducing unnecessary testing and improving appropriateness. Advances in Laboratory Medicine, 5(3), 248–260. https://doi.org/10.1515/almed-2023-0146 DOI: https://doi.org/10.1515/almed-2023-0146
Velásquez, M. A. (2022). Aseguramiento de la calidad en laboratorio clínico: Enfoque ISO 15189 y trazabilidad analítica. Pentaciencias, 4(3), 28–37. https://doi.org/10.59169/pentaciencias.v4i3.182
Villavicencio, A., Cevallos, D., & Herrera, P. (2022). Errores preanalíticos en laboratorio clínico y su impacto en seguridad del paciente: Revisión y recomendaciones operativas. Revista Ecuatoriana de Salud Pública, 9(2), 55–66. https://doi.org/10.32468/resup.v9i2.215
von Mühlen, C. A., Garcia de la Torre, I., Infantino, M., Damoiseaux, J., Andrade, L. E. C., Carballo, O. G., et al. (2021). How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: Guidelines from the ICAP initiative. Immunologic Research, 69(6), 594–608. https://doi.org/10.1007/s12026-021-09233-0 DOI: https://doi.org/10.1007/s12026-021-09233-0
Yeo, A. L., Le, S., Ong, J., Connelly, K., Ojaimi, S., Nim, H., et al. (2020). Utility of repeated antinuclear antibody tests: A retrospective database study. The Lancet Rheumatology, 2(7), e412–e417. https://doi.org/10.1016/S2665-9913(20)30084-9 DOI: https://doi.org/10.1016/S2665-9913(20)30084-9
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Salud Medicina e Innovación

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.









