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2020, Número 1

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Rev cubana med 2020; 59 (1)


Inmunocomplejos circulantes en el lupus eritematoso sistémico

Kokuin E, Milian OY, Tamargo BTO, Chico CA, Estevez TM, Andux VJL

Idioma: Español
Referencias bibliográficas: 39
Paginas: 1-15
Archivo PDF: 389.50 Kb.


RESUMEN

Introducción: Los biomarcadores son claves en el diagnóstico y pronóstico del lupus eritematoso sistémico en el cual las manifestaciones clínicas son extremadamente complejas y heterogéneas.
Objetivo: Determinar el valor clínico de los inmunocomplejos circulantes en pacientes con lupus eritematosos sistémico.
Métodos: Se determinaron los niveles séricos de inmunocomplejos fijadores del C1q y de los anticuerpos anti-ácido desoxirribonucleico de doble cadena (anti-ADNdc), antinucleosoma (anti-Nuc) y anti-proteínas ribosomales (anti-RibP) por el ensayo inmunoadsorbente ligado a enzima (ELISA) en 93 pacientes con diagnóstico de lupus eritematosos sistémico. Se utilizaron exámenes no paramétricos para probar la asociación entre los inmunocomplejos y los auto-anticuerpos. La frecuencia de nefritis lupica en los grupos de pacientes positivos y negativos de inmunocomplejos circulantes se comparó mediante Chi cuadrado.
Resultados: Los inmunocomplejos se encontraron en 24 (25,8 %) pacientes con lupus eritematosos sistémico. Los pacientes que presentaron los títulos más altos de inmunocomplejos fueron los positivos a los tres auto-anticuerpos usados (p=0,044). Se encontró correlación directa entre los niveles de anti-RibP y los inmunocomplejos (Rho=0,303, p=0,003) y entre los anti-ADNdc y anti-Nuc (Rho=0,449, p=0,001). La nefritis lúpica se presentó en 58,3 % de pacientes con inmunocomplejos, y 31,9 % pacientes negativos de inmunocomplejos (p=0,213).
Conclusiones: Los inmunocomplejos circulantes caracterizaron una fracción menor de pacientes con lupus eritematosos sistémico. La presencia de estos no se asoció a los anticuerpos anti-ADNdc ni a la nefritis lupica.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Koffler D, Agnello V, Thoburn R, Kunkel HG. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971;134:169-79.

  2. Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56:481-90.

  3. Isenberg DA, Manson JJ, Ehrenstein MR, Rahman A. Fifty years of anti-ds DNA antibodies: are we approaching journey’s end? Rheumatology. 2007;46:1052-6.

  4. Hochberg MC. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

  5. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677-86.

  6. Romero Díaz J, Isenberg D, Ramsey Goldman R. Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI- 2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Arthritis Care Res (Hoboken). 2011;63(Suppl 11):37- 46.

  7. Förger F, Matthias T, Oppermann M, Becker H, Helmke K. Clinical significance of antidsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus. 2004;14:36-44.

  8. 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.

  9. Li T, Prokopec SD, Morrison S, Lou W, Reich H, Gladman D, et al. Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus. Rheumatology (Oxford). 2014 Sep 5. pii: keu326. [Epub ahead of print].

  10. Shi ZR, Cao CX, Tan GZ, Wang L. The association of serum anti-ribosomal P antibody with clinical and serological disorders in systemic lupus erythematosus: a systematic review and meta-analysis. Lupus. 2015;24:588-96. https://doi.org/10.1177/0961203314560003

  11. Choi MY, Fitz Patrick RD, Buhler K, Mahler M, Fritzler MJ. A review and metaanalysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Autoimmun Rev. 2020;19. doi.org/10.1016/j.autrev.2020.102463

  12. Kokuina E, Estévez M, Gutiérrez A, Ortiz A, Sánchez Y, Pérez D, et al. Anticuerpos anti-nucleosoma frente a marcadores inmunológicos convencionales en el diagnóstico de la actividad del lupus eritematoso sistémico. Rev Cubana Med. 2014;53(4). Disponible en: https://www.revimedicina.sld.cu/index.php/med/login?source=%2Findex.php%2Fmed%2Fe ditor%2Fsubmission%2F1318

  13. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. 2012;64:797- 808. doi 10.1002/acr.21664.

  14. Gauthier VJ, Mannik M. A small proportion of cationic antibodies in immune complexes is sufficient to mediate their deposition in glomeruli. J Immunol. 1990;145:3348-52.

  15. Mannik M, Merrill CE, Stamps LD, Wener MH. Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus. J Rheumatol. 2003;30:1495-504.

  16. Schifferli JA, Taylor RP. Physiological and pathological aspects of circulating immune complexes. Kidney Int. 1989;35:993-1003.

  17. Jarvis JN, Diebold MM, Chadwell MK, Iobidze M, Moore HT. Composition and biological behavior of immune complexes isolated from synovial fluid of patients with juvenile rheumatoid arthritis (JRA). Clin Exp Immunol. 1995;100:514-8.

  18. Sekita K, Doi T, Muso E, Yoshida H, Kanatsu K, Hamashima Y. Correlation of C3d fixing circulating immune complexes with disease activity and clinical parameters in patients with systemic lupus erythematosus. Clin. exp. Immunol. 1984;55:487-94.

  19. Ahlin E, Mathsson L, Eloranta ML, Jonsdottir T, Gunnarsson I, Ronnblom L, et al. Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE. Lupus. 2012;21:586-95.

  20. Thanadetsuntorn C, Ngamjanyaporn P, Setthaudom C, Hodge K, Saengpiya N, Pisitkun P . The model of circulating immune complexes and interleukin-6 improves the prediction of disease activity in systemic lupus erythematosus. Scientific Reports. 2018;8:2620. https://doi:10.1038/s41598-018-20947-4

  21. Flores-Mendoza G, Sansón SP, Rodríguez-Castro S, Crispín JC, Rosetti F. Mechanisms of tissue injury in lupus nephritis. Trends Mol Med. 2018;24:364-78. https://doi.org/10.1016/j.molmed.2018.02.003

  22. Zabaleta-Lanz M, Vargas-Arenas RE, Tápanes F, Daboin I, Atahualpa Pinto J, Bianco NE, et al. Silent nephritis in systemic lupus erythematosus. Lupus. 2003;12:26-30.

  23. Hanly JG, O'Keeffe AG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology. 2016;55:252-62.

  24. Prechl J, Czirják L. The endothelial deprotection hypothesis for lupus pathogenesis: the dual role of C1q as a mediator of clearance and regulator of endothelial permeability. F1000Research. 2015;4:24. https://doi: 10.12688/f1000research.6075.2

  25. Cheung KF, Yung S, Chau MK, Yap DY, Chan KW, Lee CK, et al. Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations. Clin Sci (Lond). 2017;131:653-71. https://doi:10.1042/CS20160732

  26. Bruschi M, Galetti M, Sinico RA, Moroni G, Bonanni A, Radice A, et al. Glomerular autoimmune multicomponents of human lupus nephritis in vivo (2): planted antigens. J Am Soc Nephrol. 2015;26:1905-24. https://doi: 10.1681/ASN.2014050493

  27. Fenton K, Fismen S, Hedberg A, Seredkina N, Fenton C, Mortensen ES, et al. AntidsDNA antibodies promote initiation, and acquired loss of renal DNAse1 promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice. PLoS One. 2009;4:8474. https://doi: 10.1371/journal.pone.0008474

  28. Lefkowith, JB, Gilkeson, GS. Nephritogenic autoantibodies in lupus: current concepts and continuing controversies. Arthritis Rheum. 1996;39:894-903.

  29. Mayadas TN, Rosetti F, Ernandez T, Sethi S. Neutrophils: game changers in glomerulonephritis? Trends Mol Med. 2010;16:368-78. doi: https://10.1016/j.molmed.2010.06.002

  30. Yung S, Yap DY, Chan TM. Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis. F1000 Research. 2017;6(F1000 Faculty Rev):874. https://doi: 10.12688/f1000research.10445.1

  31. Soliman S, Mohan C. Lupus nephritis biomarkers. Clin Immunol. 2017;185:10-20. https://doi.org/10.1016/j.clim.2016.08.001

  32. Mathsson L, Ĺhlin E, Sjöwall C, Skogh T, Rönnelid J. Cytokine induction by circulating immune complexes and signs of in-vivo complement activation in systemic lupus erythematosus are associated with the occurrence of anti-Sjögren’s syndrome A antibodies. Clin Exp Immunol. 2007;147:513-520. https://doi:10.1111/j.1365-2249.2006.03313.x

  33. Ikebe K RC, Gupta RC, Tan EM. Characterization of DNA in polyethylene glycol precipitated immune complexes from sera of patients with systemic lupus erythematosus. Clin Exp Immunol. 1983;54:169-77.

  34. Nezlin R, Alarcón-Segovia D, Shoenfeld Y. Immunochemical determination of DNA in immune complexes present in the circulation of patients with systemic lupus erythematosus. J Autoimmun. 1998;11:489-93. https://doi.org/10.1006/jaut.1998.0231

  35. Abuaf N, Desgruelles C, Moumaris M, Boussa-Khettab F, Rostane H, Bellec E, et al. Detection by flow cytometry of anti-DNA autoantibodies and circulating DNA immune complexes in lupus erythematosus. J Immunol Res. 2019[acceso: 05/12/2019]. https://doi.org/10.1155/2019/6047085

  36. Tron F, Letarte J, Roque Antunes, Barreira MC, Lesavre P. Specific detection of circulating DNA: Anti-DNA immune complexes in human systemic lupus erythematosus sera using murine monoclonal anti-DNA antibody. Clin Exp Immunol. 1982;49:481-87.

  37. Sohrabian A, Ioannis Parodis I, Carlströmer-Berthén N, Frodlund M, Jönsen A, Zickert A, et al. Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus. Arthritis Res Ther. 2019;21:259. https://doi.org/10.1186/s13075-019-2056-y

  38. Abraham M, Derk CT. Anti‑ribosomal‑P antibodies in lupus nephritis, neuropsychiatric lupus, lupus hepatitis, and Chagas’ disease: promising yet limited in clinical utility. Rheumatol Int. 2015;35:27-33. https://doi 10.1007/s00296-014-3058-3

  39. Hsieh SC, Yu CL. Autoantibody profiling in systemic lupus erythematosus. Curr Biomarker Find. 2013;3:55-56. https://doi:10.2147/CBF. S34496




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