Cytokines, Autoantibodies, and Complements in Active Systemic Lupus Erythematosus Patients from Javanese Population

Yuliasih Yuliasih, Lita Diah Rahmawati, Putu Ayu Niken Amrita, Setiati Widyaningrum, Dodi Kriswanto


Systemic Lupus Erythematosus (SLE) is an autoimmune disease that has various clinical manifestations. The SLE pathogenesis involves both innate and adaptive immunological components. The system is essentially determined by genetic factors that control certain clinical and serological manifestations. Genetic traits that determine the roles of cytokines, autoantibodies, and complements in SLE vary among ethnicities. The roles of TNF-α, IL-6, anti-C1q, anti-dsDNA, C3, and C4 towards SLE activity need to be evaluated in the Javanese population. This study aimed to determine the correlation of TNF-α, IL-6, anti-C1q antibodies, anti-dsDNA, C3, and C4 with SLE activity. Forty SLE patients were diagnosed based on the American College of Rheumatology (ACR) criteria. Disease activity was measured by the Systemic Lupus Activity Measure (SLAM) index. TNF-α, IL-6, Anti-C1q, and anti-dsDNA levels were measured by ELISA, while MINIMEPH measured C3 and C4. Thirty-nine female and one male patient with SLE were diagnosed according to ACR criteria. The mean of SLAM score, anti-dsDNA, C3, and C4 levels was 20.98±6.7, 224.96±298.6, 68.70±37.08 mg/dL, and 18.75±10.69 mg/dL, respectively. Spearman's correlation test showed a positive correlation between TNF-α (r = 0.971, p<0.001), IL-6 (r=0.835, p<0.001), anti-C1q (r=0.399, p=0.01), and disease activity (SLAM score) by using. The linear regression test for TNF-α, IL-6, anti-C1q, and SLAM showed the strongest association for TNF-α (r=0.891, p<0.000). TNF-α, IL-6, and anti-C1q were correlated to disease activity in SLE patients from the Javanese population.


Systemic lupus erythematosus, tumor necrosis factor-α, interleukin-6, biomarkers

Full Text:



Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 562003. p. 481-90.

Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004;13(5):339-43.

Romero-Diaz 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 & research. 2011;63 Suppl 11:S37-46.

Umare V, Pradhan V, Nadkar M, Rajadhyaksha A, Patwardhan M, Ghosh KK, et al. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients. Mediators of Inflammation. 2014;2014:8.

Sabry A, Sheashaa H, El-Husseini A, Mahmoud K, Eldahshan KF, George SK, et al. Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its correlation with disease activity. Cytokine. 2006;35(3-4):148-53.

McCarthy EM, Smith S, Lee RZ, Cunnane G, Doran MF, Donnelly S, et al. The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients. Rheumatology (Oxford, England). 2014;53(9):1586-94.

Giles BM, Boackle SA. Linking complement and anti-dsDNA antibodies in the pathogenesis of systemic lupus erythematosus. Immunologic research. 2013;55(1-3):10-21.

Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis and rheumatism. 2004;50(7):2048-65.

Maury CPJ, Teppo AM. Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arthritis & Rheumatism. 1989;32(2):146-50.

Panafidina TA, Popkova TV, Novikov AA, Nasonov EL. AB0630 Expression of tnf-Α and il-6 in systemic lupus erythematosus: relationship with disease activity. Annals of the Rheumatic Diseases. 2018;77(Suppl 2):1462-3.

Idborg H, Eketjäll S, Pettersson S, Gustafsson JT, Zickert A, Kvarnström M, et al. TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus. Lupus Science & Medicine. 2018;5(1).

Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science (New York, NY). 2002;296(5573):1634-5.

Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-α in autoimmune diseases. Proc Natl Acad Sci U S A. 1022005. p. 3372-7.

Gabay C, Cakir N, Moral F, Roux-Lombard P, Meyer O, Dayer JM, et al. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. The Journal of rheumatology. 1997;24(2):303-8.

Garaud S, Le Dantec C, Jousse-Joulin S, Hanrotel-Saliou C, Saraux A, Mageed RA, et al. IL-6 Modulates CD5 Expression in B Cells from Patients with Lupus by Regulating DNA Methylation. The Journal of Immunology. 2009;182(9):5623-32.

Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. Journal of immunology (Baltimore, Md : 1950). 1999;163(3):1521-8.

Jacob N, Stohl W. Cytokine disturbances in systemic lupus erythematosus. Arthritis research & therapy. 2011;13(4):228.

Enocsson H, Sjowall C, Kastbom A, Skogh T, Eloranta ML, Ronnblom L, et al. Association of serum C-reactive protein levels with lupus disease activity in the absence of measurable interferon-alpha and a C-reactive protein gene variant. Arthritis & rheumatology (Hoboken, NJ). 2014;66(6):1568-73.

Richards HB, Satoh M, Shaw M, Libert C, Poli V, Reeves WH. Interleukin 6 Dependence of Anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus. The Journal of Experimental Medicine. 1998;188(5):985-90.

Fu SM, Dai C, Zhao Z, Gaskin F. Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus erythematosus. F1000Research. 2015;4(F1000 Faculty Rev).

Okamura M, Kanayama Y, Amastu K, Negoro N, Kohda S, Takeda T, et al. Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology. Annals of the Rheumatic Diseases. 1993;52(1):14-20.

MacGowan JR, Ellis S, Griffiths M, Isenberg DA. Retrospective analysis of outcome in a cohort of patients with lupus nephritis treated between 1977 and 1999. Rheumatology (Oxford, England). 2002;41(9):981-7.

López-Hoyos M, Cabeza R, Martínez-Taboada VM, Crespo J, SanSegundo D, Blanco R, et al. Clinical disease activity and titers of anti-dsDNA antibodies measured by an automated immunofluorescence assay in patients with systemic lupus erythematosus. Lupus. 2005;14(7):505-9.

Sturfelt G, Truedsson L. Complement in the immunopathogenesis of rheumatic disease. Nature reviews Rheumatology. 2012;8(8):458-68.

Nguyen CP, Cao VV, Feher J, Gergely P. Correlation between the levels of antinuclear antibodies, anti-DNA antibodies, and complement in systemic lupus erythematosus. Acta medica Hungarica. 1988;45(2):145-59.

Narayanan K, Marwaha V, Shanmuganandan K, Shankar S. Correlation between Systemic Lupus Erythematosus Disease Activity Index, C3, C4 and Anti-dsDNA Antibodies. Medical Journal, Armed Forces India. 2010;66(2):102-7.

Einav S, Pozdnyakova OO, Ma M, Carroll MC. Complement C4 is protective for lupus disease independent of C3. Journal of immunology (Baltimore, Md : 1950). 2002;168(3):1036-41.

Walport MJ. Complement and systemic lupus erythematosus. Arthritis research. 2002;4 Suppl 3:S279-93.

Moura CG, Lima I, Barbosa L, Athanazio D, Reis E, Reis M, et al. Anti-C1q antibodies: association with nephritis and disease activity in systemic lupus erythematosus. Journal of Clinical Laboratory Analysis. 2009;23(1):19-23.

Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Rönnblom L, et al. C1q inhibits immune complex–induced interferon-α production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis & Rheumatism. 2009;60(10):3081-90.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.