ABSTRACT
Objective:
To investigate the role between antibodies to extractable nuclear antigens (ENA) and clinical manifestations in a cohort of systemic lupus erythematosus (SLE) patients.
Methods:
The study included 187 adult patients with a diagnosis of SLE. Patients fulfilled the 2012 classification criteria for SLE. Full medical history, general examination, and laboratory investigations were recorded. Analyses of the autoantibodies [antinuclear antibody, anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm and anti-ribonucleoproteins (RNP)] in the serum of the patients at diagnosis were also undertaken by the routine clinical immunology laboratory at University Hospital.
Results:
The median age was 38 years, and 176 (94.1%) patients were women. Median disease duration was 120 months. Median levels of serum anti-dsDNA, complement 3 and 4 were found 211,7 IU/μL,78 mg/dL and 12,3 mg/dL. The most frequent clinical manifestation of these patients was musculoskeletal disorders (60.4%) the others were mucocutanous disorders, respectively (57.8%), nephritis (37.4%), haematological (18.7%), neurological disorders (12.3%). Anti-Sm, anti-RNP, anti-Ro and anti-La positivity were found in 15%, 24%, 26.7% and 11,8% of SLE cases. Multivariable analysis revealed that discoid rash was independent predictors of anti-Sm positivity; Raynaud phenomenon and oral ulcer were independent predictors of anti-RNP positivity; alopecia, lupus pneumonia and pericarditis were independent predictors of anti-Ro positivity and pleuritis was independent predictors of anti-La positivity.
Conclusion:
Presence of antibodies against ENAs may predict findings that may occur in the follow-up in patients with SLE and It may be useful for follow-up.
Keywords:
Systemic lupus erythematosus, clinical characteristics, immunological characteristics
References
1Wallace DJ, Hahn B. Dubois’ lupus erythematosus: Lippincott Williams & Wilkins; 2007.
2Fredi M, Cavazzana I, Quinzanini M, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus 2014;23:672-7.
3Bai Y, Tong Y, Liu Y, Hu H. Self-dsDNA in the pathogenesis of systemic lupus erythematosus. Clin Exp Immunol 2018;191:1-10.
4Aringer M. EULAR/ACR classification criteria for SLE. Seminars in arthritis and rheumatism 2019;49:S14-s7. Epub 2019/11/30.
5Agarwal S, Harper J, Kiely P. Concentration of antibodies to extractable nuclear antigens and disease activity in systemic lupus erythematosus. Lupus 2009;18:407-12.
6Bentow C, Swart A, Wu J, et al. Clinical performance evaluation of a novel rapid response chemiluminescent immunoassay for the detection of autoantibodies to extractable nuclear antigens. Clin Chim Acta 2013;424:141-7.
7Davis JM, Moder KG, Homburger HA, Ytterberg SR. Clinical features of 39 patients with antibodies to extractable nuclear antigens despite negative antinuclear antibodies: evidence for autoimmunity including neurologic and connective tissue diseases. Medicine (Baltimore) 2005;84:208-17.
8Schur PH. Laboratory evaluation of patients with systemic lupus erythematosus. Systemic lupus erythematosus: Elsevier; 2011. p. 629-53.
9Colglazier CL, Sutej PG. Laboratory testing in the rheumatic diseases: a practical review. South Med J 2005;98:185-91.
10Migliorini P, Baldini C, Rocchi V, Bombardieri S. Anti-Sm and anti-RNP antibodies. Autoimmunity 2005;38:47-54.
11Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306.
12Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1526-33.
13Vlachoyiannopoulos P, Tzavara V, Dafni U, Spanos E, Moutsopoulos H. Clinical features and evolution of antinuclear antibody positive individuals in a rheumatology outpatient clinic. J Rheumatol 1998;25:886-91.
14Satoh M, Yamagata H, Watanabe F, et al. Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjögren’s syndrome. Lupus 1995;4:63-5.
15Gaither K, Fox O, Yamagata H, Mamula M, Reichlin M, Harley J. Implications of anti-Ro/Sjögren’s syndrome A antigen autoantibody in normal sera for autoimmunity. J Clin Invest 1987;79:841-6.
16Zarmbinski MA, Messner RP, Mandel J. Anti-dsDNA antibodies in laboratory workers handling blood from patients with systemic lupus erythematosus. J Rheumatol 1992;19:1380-4.
17Li Wg, Ye Zz, Yin Zh, Zhang K. Clinical and immunological characteristics in 552 systemic lupus erythematosus patients in a southern province of China. Int J Rheum Dis 2017;20:68-75.
18Hoffman I, Peene I, Meheus L, et al. Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus. Ann Rheum Dis 2004;63:1155-8.
19Ter Borg EJ, Groen H, Horst G, Limburg PC, Wouda AA, Kallenberg CG, editors. Clinical associations of antiribonucleoprotein antibodies in patients with systemic lupus erythematosus. Semin Arthritis Rheum 1990;20:164-73.
20Alba P, Bento L, Cuadrado M, et al. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis. Ann Rheum Dis 2003;62:556-60.
21Ravirajan C, Rowse L, MacGowan J, Isenberg D. An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: a cross-sectional study. Rheumatology (Oxford) 2001;40:1405-12.
22Wang Y, Luo P, Guo T, Zou L, Shi J, Chen P. Study on the correlation between anti-ribosomal P protein antibody and systemic lupus erythematosus. Medicine (Baltimore) 2020;99: e20192.
23Franceschini F, Calzavara-Pinton P, Quinzanini M, et al. Chilblain lupus erythematosus is associated with antibodies to SSA/Ro. Lupus 1999;8:215-9.
24Lee LA, Roberts CM, Frank MB, McCubbin VR, Reichlin M. The autoantibody response to Ro/SSA in cutaneous lupus erythematosus. Arch Dermatol 1994;130:1262-8.
25Morais SA, Isenberg DA. A study of the influence of ethnicity on serology and clinical features in lupus. Lupus 2017;26:17-26.
26Franceschini F, Cretti L, Quinzanini M, Lodi Rizzini F, Cattaneo R. Deforming arthropathy of the hands in systemic lupus erythematosus is associated with antibodies to SSA/Ro and to SSB/La. Lupus 1994;3:419-22.
27Choe J-Y, Lee S-S, Kwak SG, Kim S-K. Anti-Sm Antibody, Damage Index, and Corticosteroid Use Are Associated with Cardiac Involvement in Systemic Lupus Erythematosus: Data from a Prospective Registry Study. J Korean Med Sci 2020;35:e139.
28Ryu S, Fu W, Petri MA. Associates and predictors of pleurisy or pericarditis in SLE. Lupus Sci Med 2017;4:e000221.
29Artim-Esen B, Çene E, Şahinkaya Y, et al. Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center. J Rheumatol 2014;41:1304-10.