Anticuerpos antirribosomales P, utilidad diagnóstica en el lupus eritematoso sistémico y asociación con nefritis lúpica

Elena Kokuina, Araceli Chico Capote, Miguel Estévez del Toro, Teddy Osmin Tamargo Barbeito, Ana Arguelles Zayas, Yeniset Sánchez Bruzón

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Resumen

Introducción: Los anticuerpos antirribosomales P (anti-RibP) son marcadores serológicos del lupus eritematoso sistémico (LES). Su papel en la nefritis lúpica (NL) está sometido a debate.

Objetivo: Determinar la prevalencia de los anti-RibP en pacientes cubanos con LES y examinar su asociación con la nefritis lúpica.

Métodos: Se determinaron los niveles séricos de anti-RibP y de anticuerpos antiácido desoxirribonucleico de doble cadena (anti-ADNdc) por el ensayo inmunoadsorbente ligado a enzima (ELISA) en pacientes adultos con diagnóstico de LES (n=110), otras enfermedades reumáticas (n=109) e individuos sanos (n=44). El diagnóstico de nefritis lúpica fue confirmado por criterios histopatológicos de la biopsia. La sensibilidad y especificidad para el LES se calcularon frente a otras enfermedades reumáticas.

Resultados: La sensibilidad de los anti-RibP y anti-ADNdc para el LES fue de 18,2 y 71,8 %, y la especificidad de 98,2 y 82,6 %, respectivamente. Los anti-ADNdc revelaron mayor eficiencia diagnóstica para el LES que los anti-RibP (área debajo de la curva= 0,835, IC96 %=0,781-0,890; vs. 0,557, IC95 %=0,479-0,635). No se observó dependencia de los anti-RibP de anti-ADNdc (r=0,130, p=0,177). La incidencia de NL fue superior en los pacientes anti-ADNdc+ respecto a los anti-ADNdc- (50,6 vs. 19,4 %, p=0,005), mientras que no hubo diferencias en la distribución de la NL en los pacientes anti-RibP+ respecto a los anti-RibP- (40,0 vs. 42,2%, p=0,946). La coexistencia de anti-RibP y anti-ADNdc no correspondió a mayor incidencia de nefritis lúpica (50,0 vs. 40,4%, p=0,657).

Conclusiones: La alta especificidad para el LES fue la virtud diagnóstica de los anti-RibP. Los anti-ADNdc, y no los anti-RibP, se asociaron a la nefritis lúpica.

 

Palabras clave

antirribosomales P; anti-ADN de doble cadena; lupus eritematoso sistémico; nefritis lúpica

Referencias

Rekvig OP. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clin Exp Immunol 2015; 179:5–10.

Aringer M, Costenbader KH, Daikh DI, 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: 1151-59. ISSN 0003-4967

Borchers AT, Leibushor N, Naguwa SM, Cheema GS, Shoenfeld Y, Gershwin ME. Lupus nephritis: a critical review. Autoimmun Rev 2012; 12: 174–94.

doi: 10.1016/j.autrev.2012.08.018

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.

Schmajuk G, Hoyer BF, Aringer M, Johnson SR, Daikh DI, Dörner T, et al. Multicenter Delphi exercise to identify important key items for classifying systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2018; 70: 1488–94.

Bonfa E, Elkon KB. Clinical and serological associations of the antiribosomal P protein antibody. Arthritis Rheum 1986; 29: 981–85.

Mahler M, Kessenbrock K, Szmyrka M, Takasaki Y, Garcia-De La Torre I, Shoenfeld Y, et al. International multicenter evaluation of autoantibodies to ribosomal P proteins. Clin Vaccine Immunol 2006; 13:77-83. doi.org/10.1128/CVI.13.1.77-83.2006

Lin JL, Dubljevic V, Fritzler MJ, Toh BH. Major immunoreactive domains of human ribosomal P proteins lie N-terminal to a homologous C-22 sequence: application to a novel ELISA for systemic lupus erythematosus. Clin Exp Immunol 2005; 141:155-64.

Elkon K, Skelly S, Parnassa A, Moller W, Danho W, Weissbach H, et al. Identification and chemical synthesis of a ribosomal protein antigenic determinant in systemic lupus erythematosus. Proc Natl Acad Sci USA 1986; 83: 7419–23.

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

Bonfa E, Golombek SJ, Kaufman LD, Skelly S, Weissbach H, Brot N, et al. Association between lupus psychosis and antiribosomal P protein antibodies. N Engl J Med. 1987; 317: 265–71.

Ohira H, Takiguchi J, Rai T. High frequency of anti-ribosomal P antibody in patients with systemic lupus erythematosus associated hepatitis. Hepatol Res 2004; 28: 137–39

Chindalore V, Neas B, Reichlin M. The association between anti-ribosomal P antibodies and active nephritis in systemic lupus erythematosus. Clin Immunol Immunopathol 1998; 87: 292-96.

Hirohata S . Anti-ribosomal P antibodies and lupus nephritis . Clin ExpNephrol. 2011 ; 15: 471 – 77 . DOI 10.1007/s10157-011-0462-9

Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997; 40: 1725. https://doi.org/10.1002/art.1780400928.

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.

Haddouk S , Marzouk S , Jallouli M , Fourati H , Frigui M , Hmida Y B, et al . Clinical and diagnostic value of ribosomal P autoantibodies in systemic lupus erythematosus. Rheumatology. 2009; 48: 953– 57.

Hirohata S, Kasama T, Kawahito Y, Takabayashi K. Efficacy of anti-ribosomal P protein antibody testing for diagnosis of systemic lupus erythematosus. Mod Rheumatol 2014; 24: 939–44.

Li J, Shen Y, He J, Jia R, Wang X, Chen X, et al. Significance of antibodies against the native ribosomal P protein complex and recombinant P0, P1, and P2 proteins in the diagnosis of Chinese patients with systemic lupus erythematosus. J Clin Lab Anal 2013; 27: 87–95. doi.org/10.1002/jcla.21543

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.

Mahler M, Ngo J, Schulte-Pelkum J, Luettich T, Fritzler MJ. Limited reliability of the indirect immunofluorescence technique for the detection of anti-Rib-P antibodies. Arthritis Res. Ther. 2008; 10: R131. https://doi.org/10.1186/ar2548.

Teh LS, Lee MK, Wang F, Manivasagar M, Charles PJ, Nicholson GD, et al. Antiribosomal P protein antibodies in different populations of patients with systemic

lupus erythematosus. Br J Rheumatol 1993 Aug;32:663–5.

Borba EF, Araujo DB, Bonfá E, Shinjo SK. Clinical and immunological features of 888 Brazilian systemic lupus patients from a monocentric cohort: comparison with other populations. Lupus 2013; 22: 744-49. doi: 10.1177/0961203313490432.

Morais SA, Isenberg DA. A study of the influence of ethnicity on serology and clinical features in lupus. Lupus 2017;26:17-26. doi: 10.1177/0961203316645204.

Arnett FC, Reveille JD, Moutsopoulos HM, Georgescu L, Elkon KB. Ribosomal P autoantibodies in systemic lupus erythematosus - frequencies in different ethnic

groups and clinical and immunogenetic associations. Arthritis Rheum 1996; 39: 1833–39.

Mei YJ, Wang P, Jiang C, Wang T, Chen LJ, Li ZJ, et al. Clinical and serological associations of anti-ribosomal P0 protein antibodies in systemic lupus erythematosus. Clin Rheumatol 2018; 37: 703–07. doi.org/10.1007/s10067-017-3886-0

Carmona-Fernandes D, Santos MJ, Canhao H, Fonseca JE. Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile. BMC Med 2013; 11: 98. https://doi.org/10.1186/1741-7015-11-98.

Caponi L, Chimenti D, Pratesi F, Migliorini P. Anti-ribosomal antibodies from lupus patients bind DNA. Clin Exp Immunol 2002; 130: 541–47.

Sun KH, Hong CC, Tang SJ, Sun GH, Liu WT, Han SH, et al. Anti-dsDNA autoantibody cross-reacts with the C-terminal hydrophobic cluster region containing phenylalanines in the acidic ribosomal phosphoprotein P1 to exert a cytostatic effect on the cells. Biochem Biophys Res Commun 1999; 263: 334–39.

Choi MY, FitzPatrick RD, Buhler K, Mahler M, Fritzler MJ. A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Autoimmun Rev 2020; 19: 102463. doi.org/10.1016/j.autrev.2020.102463

Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I, et al. AntidsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis. Ann Rheum Dis. 2003; 62: 556–60. https://doi.

org/10.1136/ard.62.6.556.

Kwon OC, Lee JS, Ghang B, Kim YG, Lee CK, Yoo B, et al. Predicting eventual development of lupus nephritis at the time of diagnosis of systemic lupus erythematosus. Semin Arthritis Rheum. 2018; 48: 462–66. https://doi.org/10.

/j.semarthrit.2018.02.012.

Ben-Ami Shor D, Blank M, Reuter S, Matthias T, Beiglass I, Volkov A, et al. Anti-ribosomal-P antibodies accelerate lupus glomerulonephritis and induce lupus nephritis in naïve mice. J Autoimmun 2014; 54: 118–26. doi: 10.1016/j.jaut.2014.02.013.

Massardo L, Burgos P, Martínez ME, Pérez R, Calvo M, Barros J, et al. Antiribosomal P protein antibodies in Chilean SLE patients: no association with renal disease. Lupus 2002; 11: 379–83.

Chandran V, Upadhyaya SK, Haroon N, Aggarwal A, Misra R. Lack of clinical association with antibodies to ribosomal P proteins in Indian patients with systemic lupus erythematosus. J Rheumatol. 2006; 33: 1987–89.

Barkhudarova F, Dahnrich C, Rosemann A, Schneider U, Stocker W, Burmester GR, et al. Diagnostic value and clinical laboratory associations of antibodies against recombinant ribosomal P0, P1 and P2 proteins and their native heterocomplex in a Caucasian cohort with systemic lupus erythematosus. Arthritis Res Ther 2011; 13:R20. https://doi.org/10.1186/ar3244

Quintana G, Coral-Alvarado P, Aroca G, Patarroyo PM, Chalem P, Iglesias-Gamarra A, et al. Single anti-P ribosomal antibodies are not associated with lupus nephritis in patients suffering from active systemic lupus erythematosus. Autoimmun Rev. 2010; 9: 750–55.

Kang JH, Park DJ, Choi SE, Yim YR, Kim JE, Lee JW, et al. Protective role of antiribosomal P antibody in patients with lupus nephritis. Int J Rheum Dis 2019 ; 22: 913–20.

Sarfaraz S , Anis S , Ahmed E, Muzaffar R. Clinical significance of anti-ribosomal P protein antibodies in patients with lupus nephritis. Rev Recent Clin Trials.2018; 13: 281-86. doi: 10.2174/1574887113666180409154641.

Martin AL, Reichlin M. Fluctuations of antibody to ribosomal P proteins correlate with appearance and remission of nephritis in SLE. Lupus. 1996; 5: 22–29.

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