Autoantibody profile, disease activity and organ involvement in Iranian systemic lupus erythematosus patients

Document Type: Original Article

Authors

1 Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Rheumatic Disease Research Center, Internal Medicine Department, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Autoantibodies have been implicated with increased risk of organ involvement in systemic lupus erythematosus (SLE). In the present study, we looked for autoantibody profiles and their association with clinical symptoms in a group of Iranian patients with SLE. In this study, 98 lupus patients (78 females and 20 males) were evaluated for the presence of autoantibodies against nRNP/Sm, Sm, SSA, Ro52, SSB, Scl-70, Jo-1, CENP B, nucleosomes, histones and Rib-P protein using immunoblotting technique. Anti-dsDNA was the most prevalent autoantibody (69.1%). The increased amount of autoantibodies, of the affected organs, and presence of anti-histone and anti-dsDNA correlated with disease activity. In the SLE patients with renal involvement, presence of anti-nucleosome (54.8% vs. 39.4%, P= 0.04) and decreased levels of anti-SSB (14.3% vs. 26.3%, P= 0.007) were significantly different campared with patients without renal involvement. Our results showed that elevated levels of autoantibodies including anti-dsDNA and anti-histone, and increasing number of involved organs, could be used as predictors for assessment of disease activity in patients with lupus. In addition, the increased levels of anti-nucleosome and the lower occurrence of anti-SSB could be used in the verification of renal damage. 

Keywords


 Fu SM, Deshmukh US, Gaskin F. Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. J Autoimmun 2011; 37(2): 104-12. doi: 10.1016/j.jaut.2011.05.004.

Croker JA, Kimberly RP. SLE: challenges and candidates in human disease. Trends Immunol 2005; 26(11):580-6. doi: 10.1016/j.it.2005. 09.001.

Waldman M, Madaio MP. Pathogenic autoantibodies in lupus nephritis. Lupus 2005; 14(1): 19-24.

Fernando MM, Isenberg DA. How to monitor SLE in routine clinical practice. Ann Rheum Dis 2005; 64(4):524-7. doi: 10.1136/ard.2003. 015248.

Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349(16): 1526-33. doi: 10. 1056/NEJMoa021933.

Yee CS, Hussein H, Skan J, Bowman S, Situnayake D, Gordon C. Association of damage with autoantibody profile, age, race, sex and disease duration in systemic lupus erythematosus. Rheumatology (Oxford) 2003; 42(2): 276-9.

Eriksson C, Kokkonen H, Johansson M, Hallmans G, Wadell G, Rantapaa-Dahlqvist S. Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden. Arthritis Res Ther 2011; 13(1):R30. doi: 10.1186/ar3258.

Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med 2005; 201(5):703-11. doi: 10.1084/ jem.20042251.

Ohashi PS, DeFranco AL. Making and breaking tolerance. Curr Opin Immunol 2002; 14(6): 744-59.

Bijl M, Horst G, Limburg PC, Kallenberg CG. Anti-CD3-inducedand anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE). Clin Exp Immunol 2001; 123(1): 127-32.

Bijl M, Limburg PC, Kallenberg CG. New insights into the pathogenesis of systemic lupus erythematosus (SLE): the role of apoptosis. Neth J Med 2001; 59(2): 66-75.

Dieker JW, van der Vlag J, Berden JH. Triggers for anti-chromatin autoantibody production in SLE. Lupus 2002; 11(12): 856-64.

Rastin M, Hatef MR, Tabasi N, Mahmoudi M. The pathway of estradiolinduced apoptosis in patients with systemic lupus erythematosus. Clin Rheumatol 2012; 31(3):417-24. doi: 10.1007/ s10067-011-1821-3.

Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocytederived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41(7): 1241-50. doi: 10.1002/ 1529-0131(199807)41:7< 1241: AID-ART15>3.0.CO; 2-H.

Reefman E, Dijstelbloem HM, Limburg PC, Kallenberg CG, Bijl M. Fcgamma receptors in the initiation and progression of systemic lupus erythematosus. Immunol Cell Biol 2003; 81(5): 382-9. doi: 10.1046/j.1440-1711. 2003.01188.x.

Mevorach D, Zhou JL, Song X, Elkon KB. Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 1998; 188(2): 387-92.

Cortes-Hernandez J, Ordi-Ros J, Labrador M, Bujan S, Balada E, Segarra A, et al. Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med 2004; 116(3): 165-73.

van der Vlag J, Berden JH. Lupus nephritis: role of antinucleosome autoantibodies. Semin Nephrol 2011; 31(4): 376-89. doi: 10.1016/j.semnephrol.2011.06.009.

Manson JJ, Ma A, Rogers P, Mason LJ, Berden JH, van der Vlag J, et al. Relationship between anti-dsDNA, anti-nucleosome and anti-alphaactin in antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res Ther 2009; 11(5): R154. doi: 10.1186/ar2831.

Gomez-Puerta JA, Burlingame RW, Cervera R. Anti-chromatin (antinucleosome) antibodies: diagnostic and clinical value. Autoimmun Rev 2008; 7(8):606–11. doi: 10.1016/j.autrev.2008.06. 005.

Solomon DH, Kavanaugh AJ, Schur PH, American College of Rheumatology Ad Hoc Committee on Immunologic Testing G. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002; 47(4): 434-44. doi: 10.1002/art.10561.

Shariati-Sarabi Z, Monzavi SM, Ranjbar A, Esmaily H, Etemadrezaie H. High disease activity is associated with high disease damage in an Iranian inception cohort of patients with lupus nephritis. Clin Exp Rheumatol 2013; 31(1):69-75.

Sherer Y, Gorstein A, Fritzler MJ, Shoenfeld Y. Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 2004; 34(2): 501-37.

Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol 2010; 125(2 Suppl 2): S238–47. doi: 10.1016/j.jaci.2009. 09.041.

Doria A, Zen M, Canova M, Bettio S, Bassi N, Nalotto L, et al. SLE diagnosis and treatment: when early is early. Autoimmun Rev 2010; 10(1): 55-60. doi: 10.1016/j.autrev. 2010.08.014.

Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000; 53(6): 424-32. Autoantibody profile and SLE

 Olsen NJ, Yousif M, Mutwally A, Cory M, Elmagboul N, Karp DR. Organ damage in high-risk patients with systemic and incomplete lupus syndromes. Rheumatol Int 2013; 33(10): 2585-90. doi: 10.1007/s00296-013-2783-3.

Ong C, Nicholls K, Becker G. Ethnicity and lupus nephritis: an Australian single centre study. Intern Med J 2011; 41(3): 270–8. doi: 10.1111/j.1445-5994.2009.02159.x.

de Zubiria Salgado A, Herrera-Diaz C. Lupus nephritis: an overview of recent findings. Autoimmune Dis 2012; 2012:849684. doi: 10.1155/2012/849684.