Gumilang, Retna (2018) Efek Pemberian Escalating Dose Immunotherapy (EDI) Menggunakan Self Antigen dsDNA terhadap Jumlah Sel T Helper 1 (Th1) dan Kadar Interferon Gamma (IFN-γ) pada Mencit Lupus Induksi Pristane. Magister thesis, Universitas Brawijaya.
Abstract
Lupus Eritematosus Sistemik (LES) adalah penyakit autoimun, ditandai keradangan sistemik kronis yang melibatkan kerusakan multi organ. LES di dunia mencapai 5 juta orang dan 200.000 diantaranya di Indonesia. Penderitanya didominasi wanita usia produktif. LES diakibatkan oleh sistem imun bereaksi berlebihan terhadap antigen sendiri, akibatnya terjadi reaksi inflamasi sistemik dan kerusakan organ. Pada pasien LES terbukti mengalami abnormalitas regulasi sistem imun. Ditandai dengan peningkatan sel plasma di darah tepi yang berkorelasi dengan kadar anti-dsDNA, Hal ini membuat sel plasma dan anti-dsDNA berpotensi dijadikan target terapi untuk manifestasi klinis LES. Penelitian lain menunjukkan bahwa terdapat sitokin proinflamasi yang berperan penting dalam pathogenesis LES yaitu Interferon Gamma (IFN-γ) yang merupakan sitokin paling banyak diproduksi sel Th1 untuk mempengaruhi aktivitas sistem imun, salah satunya adalah aktivasi dan diferensiasi dari sel B menjadi sel plasma sehingga akan memproduksi autoantibodi anti-dsDNA. EDI adalah metode untuk mensupresi respon imun melaui mekanisme toleransi dengan cara menginjeksikan self-antigen yang menstimulus pembentukan autoantibodi dengan dosis bertahap hingga memunculkan efek toleransi dan desensitisasi. Penelitian ini dilakukan untuk mengetahui efek EDI dsDNA pada mencit lupus induksi pristane terhadap penurunan jumlah sel Th1 diukur dengan metode flowcytometry dari jaringan spleen mencit dan kadar IFN-γ diukur menggunakan metode ELISA. Penelitian ini merupakan penelitian true experimental laboratorik dengan menggunakan post test only controlled group design, secara in vivo dengan mencit strain BALB/c betina sebagai subjek yang dibagi dalam lima kelompok besar sebagai berikut : Kontrol negatif (K-), yaitu mencit normal. Kontrol positif (K+), yaitu mencit lupus induksi pristane.Kelompok A yaitu mencit lupus induksi pristane dan dsDNA konsentrasi I (0. 01 μg/ml, 0. 1 μg/ml, 1 μg/ml). Kelompok B yaitu mencit lupus induksi pristane dan dsDNA konsentrasi II (0. 1 μg/ml, 1 μg/ml, 10 μg/ml) dan kelompok C yaitu mencit lupus induksi pristane dan dsDNA konsentrasi III (1μg/ml, 10 μg/ml, 100 μg/ml). Hasil penelitian, mencit lupus induksi pristane setelah 12 minggu menunjukkan penurunan berat badan (60%), bulu rontok (70%), penurunan aktivitas (50%) dan peningkatan kadar anti-dsDNA. Analisis uji beda jumlah sel Th1 dengan One Way Anova didapatkan nilai p= 0,773. Hasil uji beda Kruskal Wallis Kadar IFN-γ didapatkan p=0,020. uji non parametrik Mann whitney didapatkan mencit kelompok terapi dsDNA dengan dosis I (p=0.021) dan II (p=0.021) mengalami penurunan yang signifikan. Dari hasil penelitian diatas dapat disimpulkan bahwa pemberian EDI dsDNAmampu memperbaiki regulasi sistem imun pada mencit model Pristane Induced Lupus (PIL) yang ditunjukkan dengan adanya penurunan jumlah sel T Helper 1 (Th1) dan kadar Interferon Gamma (IFN-γ) pada kelompok A dan B.
English Abstract
Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by chronic systemic inflammation involving multi-organ damage. SLE in the world reaches 5 million people and 200,000 of them in Indonesia. Patients dominated women of productive age. SLE is caused by the immune system overreacting to the antigen itself, resulting in systemic inflammatory reactions and organ damage. In SLE patients proved to have abnormalities of immune system regulation. Characterized by elevated plasma cells in peripheral blood correlated with anti-dsDNA levels, this makes plasma and anti-dsDNA cells potentially targeted as treatment for clinical manifestations of SLE. Other studies have shown that there is a proinflammatory cytokine that plays an important role in the pathogenesis of SLE, ie Interferon Gamma (IFN-γ), which is the most Th1 cell produced cytokine to influence immune system activity, one of which is the activation and differentiation of B cells into plasma cells that will produce anti-dsDNA autoantibodies. EDI is a method for suppressing the immune response through the mechanism of tolerance by injecting self-antigens that stimulate the formation of autoantibodies with a gradual dose to elicit the effects of tolerance and desensitization. This study was conducted to investigate the effect of EDI dsDNA on pristane induction lupus mice to decrease of Th1 cell number measured by flowcytometry method from mouse spleen tissue and IFN-ɣ level was measured using ELISA method. This study was a true experimental laboratory study using post test only controlled group design, in vivo with mice BALB / c female strain as subjects divided into five major groups as follows: Negative control (K-), ie normal mice. Positive control (K +), ie premene induction lupus mice. Group A is induced lupus induction of pristane and dsDNA concentration I (0. 01 μg/ml, 0. 1 μg/ml, 1 μg/ml). Group B were premene induction lupus mice and ds DNA concentrations of II (0. 1 μg/ml, 1 μg/ml, 10 μg/ml) and group C were premene induction lupus mice and dsDNA concentration III (1μg/ml, 10 μg/ml, 100 μg/ml). Results of the study, mice pristane induce lupusafter 12 weeks showed weight loss (60%), hair loss (70%), decreased activity (50%) and increased anti-dsDNA levels. Analysis of difference test of Th1 cell number with One Way Anova got value p = 0,773. Different test results Kruskal Wallis IFN-γ levels obtained p = 0.020. non parametric test of Mann Whitney was obtained by mice of dsDNA therapy group with dose I (p = 0.021) and II (p = 0.021) had significant decrease. From the above results it can be concluded that EDI dsDNA improves immune system regulation in Pristane Induced Lupus (PIL) model mice as indicated by a decrease in the number of Helper 1 (Th1) T cells and Interferon Gamma (IFN-γ) levels in groups A and B.
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/616.772/GUM/e/2018/041802683 |
| Uncontrolled Keywords: | LUPUS ERYTHEMATOSUS, INIMUNOTHERAPY, ANTIGENS, T CELLS, INTERFERON |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.7 Diseases of musculoskeletal system > 616.77 Diseases of connectives tissues |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | Nur Cholis |
| Date Deposited: | 11 May 2018 02:37 |
| Last Modified: | 22 Oct 2021 00:56 |
| URI: | http://repository.ub.ac.id/id/eprint/10369 |
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