Escalating Dose Antigen Specific Therapy with dsDNA Injection Regulate Balance Ratio of Inflammatory Cells in Pristane-Induced Lupus Mice Model

sri poeranto

= http://dx.doi.org/10.20473/jscrte.v3i1.16329
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Abstract


Immunosuppressant and steroid therapy for SLE have not shown satisfactory results. Another method of therapy that is being developed is vaccines and escalating dose immunotherapy using self-antigen. The aim of this study was to assess the balance of immune cells through the ratio of pro-inflammatory and anti-inflammatory cells and cytokines in SLE using self-antigen dsDNA therapy. Methods: Female Balb/c mice 6-8 weeks old separated randomly to negative control group and pristane induced lupus (PIL) mice group. PIL mice groups were injected pristane intraperitoneally. Twelve weeks after the injection, the mice were evaluated for clinical and serological manifestations (anti-dsDNA levels). Mice with lupus signs were divided into four groups; positive control group: PIL mice without EDI dsDNA therapy, treatment A: PIL mice with EDI dsDNA therapy dose I (0.01μg/ml, 0.1μg/ml, 1μg/ml), treatment B: PIL mice with EDI dsDNA therapy dose II (0.1μg/ml, 1μg/ml, 10μg/ml), and treatment C: PIL mice with EDI dsDNA therapy dose III (1μg/ml, 10μg/ml, 100μg/ml). dsDNA were injected once a week and the dose was increased every week. Samples were analyzed for active/inactive dendritic cells ratio, Th1/Th2 cells ratio, Th17/Treg cells ratio and IL-17/TGF-β levels ratio. Results: Escalating dose antigen specific therapy with dsDNA injection of third dose reduced active/inactive dendritic cells ratio (p=0.000), Th1/Th2 cells ratio (p=0.010), Th17/Treg ratio (p=0.004) and decrease IL-17/TGF- β levels ratio (p=0.004) significantly compared to positive control. Conclusion: Escalating dose antigen specific therapy with dsDNA injection of dose III was able to regulate balance ratio of inflammatory cells and cytokines in PIL mice thus the immune tolerance may improve compared to control groups.

Keywords


systemic lupus erythematosus, dsDNA, escalating dose, tolerance

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Afzali B, Lombardi G, Lechler R I and Lord G M 2007 The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease J Clin Exp Immunol. 148 32–46.

Akahoshi M et al 1999 Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum. 42 1644–8.

Anderson P O, Manzo B A, Sundstedt A, Minaee S, Symonds A, Khalid S, Rodriguez‐Cabezas M E, Nicolson K, Li S, Wraith D C and Wang P 2006 Persistent antigenic stimulation alters the transcription program in T cells, resulting in antigen-specific tolerance Eur J Immunol. 36 1374–85.

Apostolidis S A, Crispín J C and Tsokos G C 2011 IL-17-producing T cells in lupus nephritis. Lupus. 20 120-4.

Burton BR, Britton GJ, Fang H, Verhagen J, Smithers B, Sabatos-Peyton C A, Carney L J, Gough J, Strobel S, Wraith D C 2014 Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy Nat Commun. 5 4741

Campbell J D, Buckland K F, McMillan S J, Kearley J, Oldfield W L G, Stern LJ, Grönlund H, van Hage M, Reynolds C J, Boyton R J and Cobbold S P 2009 Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression J Exp Med.206 1535–47.

Choi J, Kim S T and Craft J 2012 The pathogenesis of systemic lupus erythematosus-an update. Curr Opin Immunol. 24 651–7.

Crispin J C and Tsokos G C 2009 Human TCR- + CD4- CD8- T cells can derive from CD8+ T cells and display an inflammatory effector phenotype J Immunol. 183 4675–81.

Crispín J C, Oukka M, Bayliss G, Cohen R A, Van Beek C A, Stillman I E, Kyttaris V C, Juang Y T and Tsokos G C 2008 Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys J Immunol. 181 8761–6.

Dolff S, Bijl M, Huitema M G, Limburg P C, Kallenberg C G M and Abdulahad W H 2011 Disturbed Th1, Th2, Th17 and Treg balance in patients with systemic lupus erythematosus Clin Immunol. 141 197–204.

El-Sayed M, Nofal E, Mokadem S Al, Makhzangy I Al, Gaballah H and Akl H 2008 Correlative study of serum Th1/Th2 cytokines levels in patients with systemic lupus erythematosus with SLEDAI. Egypt Dermatol Online J. 4

Elias K M, Laurence A, Davidson T S, Stephens G, Kanno Y, Shevach E M and O'Shea J J 2008 Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway Blood. 111 1013–20.

Fousteri G, Dave A, Bot A, Juntti T, Omid S and Von Herrath M 2010 Subcutaneous insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFNγ Diabetologia. 53 1958–70.

Gabrysová L, Nicolson KS, Streeter HB, Verhagen J, Sabatos-Peyton CA, Morgan DJ and Wraith D J 2009 Negative feedback control of the autoimmune response through antigen-induced differentiation of IL- 10-secreting Th1 cells J Exp Med. 206 1755–67.

Guimarães P M et al. 2017 Cytokines in systemic lupus erythematosus: Far beyond Th1/Th2 dualism lupus: Cytokine profiles. Immunol Cell Biol. 95 824–31.

Handono K, Marisa D and Kalim H 2013 Association between the low levels of vitamin D and Treg function in systemic lupus erythematosus patients. Acta Med Indones. 45 26–31.

Huang L et al 2012 Engineering DNA Nanoparticles as Immunomodulatory Reagents that Activate Regulatory T Cells J Immunol. 188 4913–20.

Kimura A and Kishimoto T 2010 IL-6: Regulator of Treg/Th17 balance Eur J Immunol. 40 1830–5.

Larché M and Wraith D C 2005 Peptide-based therapeutic vaccines for allergic and autoimmune diseases Nat Med. 11 S69

Ma J, Yu J, Tao X, Cai L, Wang J and Zheng S G 2010 The imbalance between regulatory and IL-17-secreting CD4+ T cells in lupus patients Clin Rheumatol. 29 1251–8.

Miyake K, Akahoshi M and Nakashima H 2011 Th subset balance in lupus nephritis. J Biomed Biotechnol 2011.

Pathak S and Mohan C 2011 Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models. Arthritis Res Ther. 13 241.

Plantinga M et al 2011 Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen Immunity 38 322–35.

Pusdatin Kementerian Kesehatan 2017 Situasi Lupus di Indonesia (Infodatin – Jakarta) ISSN: 2442-7569

Postal M, Peliçari K O, Sinicato N A, Marini R, Costallat L T L and Appenzeller S 2013 Th1/Th2 cytokine profile in childhood-onset systemic lupus erythematosus. Cytokine. 61 785–91.

Sawla P, Hossain A, Hahn B H, Singh R P 2012 Regulatory T cells in systemic lupus erythematosus (SLE); Role of peptide tolerance Autoimmun Rev. 11 611–4.

Schwarting A, Wada T, Kinoshita K, Tesch G and Kelley V R 1998 IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice J Immunol. 161 494–503.

Shah K, Lee W W, Lee S H, Kim SH, Kang SW, Craft J and Kang I 2010 Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus Arthritis Res Ther. 12 R53.

Singh-Jasuja H, Thiolat A, Ribon M, Boissier MC, Bessis N, Rammensee HG and Decker P 2013 The mouse dendritic cell marker CD11c is down-regulated upon cell activation through Toll-like receptor triggering Immunobiology 218 28–39

Tarzi M, Klunker S, Texier C, Verhoef A, Stapel S O, Akdis C A, Maillere B, Kay A B and Larche M 2006 Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy 36 465–74.

Theofilopoulos A N, Koundouris S, Kono D H and Lawson B R 2001 The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity. Arthritis Res. 3 136–41.

Tsokos G C, Lo M S, Reis P C and Sullivan K E 2016 New insights into the immunopathogenesis of systemic lupus erythematosus Nat Rev Rheumatol. 12. 716

Wichainun R, Kasitanon N, Wangkaew S, Hongsongkiat S, Sukitawut W and Louthrenoo W 2013 Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: A comparison using control sera obtained from healthy individuals and patients with multiple medical problems. Asian Pac J Allergy Immunol. 31 292–8.

Xu D, Liu H, Komai-Koma M, Campbell C, McSharry C, Alexander J and Liew F Y 2003 CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, leishmania major infection, and colitis in mice J Immunol 170 394–9.

Yang J, Yang X, Zou H, Chu Y and Li M 2011 Recovery of the immune balance between Th17 and regulatory T cells as a treatment for systemic lupus erythematosus Rheumatology (Oxford) 50 1366–72.

Yap D Y H and Lai K N 2010 Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: From basics to recent advances. J Biomed Biotechnol. 2010.

Zhu J and Mohan C 2007 SLE 1, 2, 3⋯Genetic dissection of lupus. In: Immune Mediated Disease – From Theory to Therapy (Springer-New York)


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