TY - GEN
T1 - Efficacy studies of Treg activation using dsDNA desensitization inhibits immune function without side effect in lupus mice model
AU - Albaar, Thoha M.
AU - Handono, Kusworini
AU - Poeranto, Sri
AU - Nurdiana,
AU - Arifin, Syaiful
AU - Hartanti, Khoirunisah D.
AU - Gumilang, Retna
AU - Dharmesta, Naya A.
AU - Saputri, Nadya V.
AU - Anggita, Aviola
AU - Dananjaya, Vigyan
N1 - Publisher Copyright:
© 2019 Author(s).
PY - 2019/6/4
Y1 - 2019/6/4
N2 - The aim of this study was to develop a novel therapeutic method for improving immune system regulation in SLE using escalating dose self-antigen dsDNA immunotherapy. Female Balb/c mice were given a single intraperitoneal injection of 0.5 ml pristane. Starting at 12 weeks after injection, the mice were evaluated for clinical and serological manifestations. Mice with lupus signs (PIL mice) were divided into two groups; a positive control group and PIL (0.1 μg/ml, 1 μg/ml, 10 μg/ml) EDI dsDNA group. EDI dsDNA was administered once every week in consecutively. The doses would increase every week. dsDNA was complexed with the cationic polyethyleneimine (PEI) before injection. Samples were analyzed for autoantibodies levels (dsDNA, ANA) and TGF-β cytokine from serum using ELISA and T-Reg, mature dendritic cells from spleen using flowcytometry. Liver and kidney function was measured by ALT/AST, Ur/Cr, Proteinuria and ALP serum. Efficacy study result showed that immune profile, inflammation marker, proteinuria, liver and renal functions were improved. significantly decreased ANA (p=0.02), anti-dsDNA (p=0.03), dendritic cell mature (p=0.02) compare to positive control, and not significantly decreases Th17 cells (p=0,18) but the result tend to get lower. Desensitization using self-antigen dsDNA was increased T-reg proliferation (p=0.00) and level of TGF-β (p=0.03) significantly compare to positive control. Analysis for side effect revealed that PIL with EDI dsDNA decrease SGOT(p=0.87) SGPT (p=0.22), Ureum (p=0.009), Creatinin (p=0,87), Proteinuria (p=0.009) and ALP (p=0,65) compared to positive control. Desensitization using self-antigen dsDNA coupled to PEI was able to modulate T-Reg as a regulator immune respon and inhibit B and T cell functions and potential to be developed further as new, safe and effective immunotherapy against pristane-induced SLE BALB/c mice.
AB - The aim of this study was to develop a novel therapeutic method for improving immune system regulation in SLE using escalating dose self-antigen dsDNA immunotherapy. Female Balb/c mice were given a single intraperitoneal injection of 0.5 ml pristane. Starting at 12 weeks after injection, the mice were evaluated for clinical and serological manifestations. Mice with lupus signs (PIL mice) were divided into two groups; a positive control group and PIL (0.1 μg/ml, 1 μg/ml, 10 μg/ml) EDI dsDNA group. EDI dsDNA was administered once every week in consecutively. The doses would increase every week. dsDNA was complexed with the cationic polyethyleneimine (PEI) before injection. Samples were analyzed for autoantibodies levels (dsDNA, ANA) and TGF-β cytokine from serum using ELISA and T-Reg, mature dendritic cells from spleen using flowcytometry. Liver and kidney function was measured by ALT/AST, Ur/Cr, Proteinuria and ALP serum. Efficacy study result showed that immune profile, inflammation marker, proteinuria, liver and renal functions were improved. significantly decreased ANA (p=0.02), anti-dsDNA (p=0.03), dendritic cell mature (p=0.02) compare to positive control, and not significantly decreases Th17 cells (p=0,18) but the result tend to get lower. Desensitization using self-antigen dsDNA was increased T-reg proliferation (p=0.00) and level of TGF-β (p=0.03) significantly compare to positive control. Analysis for side effect revealed that PIL with EDI dsDNA decrease SGOT(p=0.87) SGPT (p=0.22), Ureum (p=0.009), Creatinin (p=0,87), Proteinuria (p=0.009) and ALP (p=0,65) compared to positive control. Desensitization using self-antigen dsDNA coupled to PEI was able to modulate T-Reg as a regulator immune respon and inhibit B and T cell functions and potential to be developed further as new, safe and effective immunotherapy against pristane-induced SLE BALB/c mice.
KW - dsDNA
KW - escalating dose
KW - Systemic Lupus Erythematosus
KW - tolerance
KW - Tregulator
UR - https://www.scopus.com/pages/publications/85067024560
U2 - 10.1063/1.5110012
DO - 10.1063/1.5110012
M3 - Conference contribution
AN - SCOPUS:85067024560
T3 - AIP Conference Proceedings
BT - International Conference on Bioinformatics and Nanomedicine from Natural Resources for Biomedical Research
A2 - Budianto, Windy Yuliana
A2 - Sujuti, Hidayat
A2 - Khotimah, Husnul
PB - American Institute of Physics Inc.
T2 - 3rd Annual Scientific Meeting of Indonesian Consortium for Biomedical Sciences, ASMICBS 2018
Y2 - 21 November 2018 through 23 November 2018
ER -