Palabras clave
Citometría de flujo
Subpoblaciones de linfocitos
Marcadores diagnósticos
Resumen
Objetivo: Evaluar la asociación entre el perfil linfoide ampliado y los errores innatos de la inmunidad mediante citometría de flujo.
Métodos: Estudio observacional y transversal, de casos y controles, llevado a cabo en pacientes con diagnóstico o sospecha clínica de errores innatos de la inmunidad, atendidos en el Hospital de Niños de la Santísima Trinidad de Córdoba, Argentina, de agosto de 2021 a noviembre de 2022. Se recolectaron los datos clínicos y se obtuvieron muestras de sangre periférica para el análisis por citometría de flujo, mediante el tubo PIDOT, para identificar subpoblaciones de linfocitos alteradas. Para el análisis estadístico se utilizó la prueba exacta de Fisher, razón de momios y modelo de regresión logística binaria.
Resultados: Se analizaron 40 casos y 20 controles. Las subpoblaciones de linfocitos más frecuentemente alteradas fueron: CD4+ n (63%), Mem c/s (60%) y Mem s/s (55%). Se encontró asociación estadísticamente significativa entre varias subpoblaciones de linfocitos y el estado de salud-enfermedad. La regresión logística binaria reportó Mem s/s y CD4+n como las subpoblaciones de linfocitos alteradas con mayor probabilidad de padecer errores innatos de la inmunidad.
Conclusión: Este estudio contribuye a mejorar la comprensión de los errores innatos de la inmunidad, y demuestra una sólida asociación con los perfiles de subpoblaciones de linfocitos alteradas. Los Mem s/s y CD4+n emergen como biomarcadores relevantes para su diagnóstico. La heterogeneidad en diferentes enfermedades y en la citometría de flujo subraya la importancia de evaluar a cada paciente individualmente, para mejorar el diagnóstico y tratamiento.
Palabras Clave: Errores innatos de la inmunidad; Citometría de flujo; Subpoblaciones de linfocitos; marcadores diagnósticos.
Referencias
Gonzalez de la Calle V, Pérez-Andrés M, Puig Morón N. Inmunodeficiencias primarias. Med - Programa Form Médica Contin Acreditado. 2016; 12 (21): 1191-1200. doi: 10.1016/j.med.2016.10.010
Picard C, Gaspar BH, Al-Herz W, et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 2018; 38 (1): 96-128. doi: 10.1007/s10875-017-0464-9
Knight V. The utility of flow cytometry for the diagnosis of primary immunodeficiencies. Int J Lab Hematol 2019; 41 (S1): 63-72. doi: 10.1111/ijlh.13010
Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol 2018; 38 (1): 129-143. doi: 10.1007/s10875-017-0465-8
Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022: 1-35. doi: 10.1007/s10875-022-01289-3
Bousfiha A, Moundir A, Tangye SG, et al. The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity. J Clin Immunol 2022; 42 (7): 1508-1520. doi: 10.1007/s10875-022-01352-z
Kanegane H, Hoshino A, Okano T, et al. Flow cytometry-based diagnosis of primary immunodeficiency diseases. Allergol Int 2018; 67 (1): 43-54. doi: 10.1016/j.alit.2017.06.003
Conley ME, Notarangelo LD, Etzioni A. Diagnostic Criteria for Primary Immunodeficiencies. Clin Immunol 1999; 93 (3): 190-197. doi:10.1006/clim.1999.4799
van Dongen JJM, van der Burg M, Kalina T, et al. EuroFlow-Based Flowcytometric Diagnostic Screening and Classification of Primary Immunodeficiencies of the Lymphoid System. Front Immunol 2019; 10. https://www.frontiersin.org/articles/10.3389/fimmu.2019.01271
van der Burg M, Kalina T, Perez-Andres M, et al. The EuroFlow PID Orientation Tube for Flow Cytometric Diagnostic Screening of Primary Immunodeficiencies of the Lymphoid System. Front Immunol 2019. doi: 10.3389/fimmu.2019.00246
Edwards ESJ, Bosco JJ, Aui PM, et al. Predominantly Antibody-Deficient Patients with Non-infectious Complications Have Reduced Naive B, Treg, Th17, and Tfh17 Cells. Front Immunol. 2019; 10. https://www.frontiersin.org/articles/10.3389/fimmu.2019.02593
Attardi E, Di Cesare S, Amodio D, et al. Phenotypical T Cell Differentiation Analysis: A Diagnostic and Predictive Tool in the Study of Primary Immunodeficiencies. Front Immunol 2019; 10. https://www.frontiersin.org/articles/10.3389/fimmu.2019.02735
Ma CS, Tangye SG. Flow Cytometric-Based Analysis of Defects in Lymphocyte Differentiation and Function Due to Inborn Errors of Immunity. Front Immunol 2019; 10. https://www.frontiersin.org/articles/10.3389/fimmu.2019.02108
Yaakoubi R, Mekki N, Ben-Mustapha I, et al. Diagnostic challenge in a series of eleven patients with hyper IgE syndromes. Front Immunol 2023; 13. https://www.frontiersin.org/articles/10.3389/fimmu.2022.1057679
Ahmed A, Lippner E, Khanolkar A. Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future. Cells 2022; 11 (21): 3353. doi: 10.3390/cells11213353
Kalina T, Bakardjieva M, Blom M, et al. EuroFlow Standardized Approach to Diagnostic Immunopheneotyping of Severe PID in Newborns and Young Children. Front Immunol. 2020; 11. https://www.frontiersin.org/articles/10.3389/fimmu.2020.00371
Locke BA, Dasu T, Verbsky JW. Laboratory Diagnosis of Primary Immunodeficiencies. Clin Rev Allergy Immunol 2014; 46 (2): 154-168. doi: 10.1007/s12016-014-8412-4
Frugoni F, Dobbs K, Felgentreff K, et al. A novel mutation in the POLE2 gene causing combined immunodeficiency. J Allergy Clin Immunol 2016; 137 (2): 635-638.e1. doi: 10.1016/j.jaci.2015.06.049
Giraldo-Ocampo S, Bonelo A, Zea-Vera AF. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv Respir Med 2022; 90 (4): 254-266. doi: 10.3390/arm90040035
Álvarez-Álvarez JA, Duque AG, Vásquez-Echeverri E, et al. Application of the diagnostic criteria for Common Variable Immunodeficiency in resource-limited settings. Allergol Immunopathol (Madr) 2022; 50 (4): 129-136. doi: 10.15586/aei.v50i4.496
Seidel MG, Kindle G, Gathmann B, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract 2019; 7 (6): 1763-1770. doi: 10.1016/j.jaip.2019.02.004
Martelius T, Seppänen MRJ, Warnatz K. Editorial: Updates on the pathogenesis of common variable immunodeficiency (CVID). Front Immunol 2023; 13. https://www.frontiersin.org/articles/10.3389/fimmu.2022.1130418
Fekrvand S, Khanmohammadi S, Abolhassani H, et al. B- and T-Cell Subset Abnormalities in Monogenic Common Variable Immunodeficiency. Front Immunol 2022; 13. https://www.frontiersin.org/articles/10.3389/fimmu.2022.912826
Ameratunga R, Brewerton M, Slade C, et al. Comparison of Diagnostic Criteria for Common Variable Immunodeficiency Disorder. Front Immunol 2014; 5. https://www.frontiersin.org/articles/10.3389/fimmu.2014.00415
Bonilla FA, Barlan I, Chapel H, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract 2016; 4 (1): 38-59. doi: 10.1016/j.jaip.2015.07.025
Stuchlý J, Kanderová V, Vlková M, et al. Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia. Sci Rep 2017; 7 (1): 39710. doi: 10.1038/srep39710
Szczawinska-Poplonyk A, Schwartzmann E, Bukowska-Olech E, et al. The pediatric common variable immunodeficiency — from genetics to therapy: a review. Eur J Pediatr. 2022; 181 (4): 1371-1383. doi: 10.1007/s00431-021-04287-6
Jhamnani RD, Nunes-Santos CJ, Bergerson J, Rosenzweig SD. Class-Switch Recombination (CSR)/Hyper-IgM (HIGM) Syndromes and Phosphoinositide 3-Kinase (PI3K) Defects. Front Immunol 2018; 9: 2172. doi: 10.3389/fimmu.2018.02172
Cabral-Marques O, Schimke LF, de Oliveira EB, et al. Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation. Front Immunol 2019; 10. https://www.frontiersin.org/articles/10.3389/fimmu.2019.02742
Habibi S, Zaki-Dizaji M, Rafiemanesh H, et al. Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review. J Allergy Clin Immunol Pract 2019; 7 (7): 2379-2386.e5. doi: 10.1016/j.jaip.2019.04.011
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