Perbedaan ekspresi gen untuk proses netosis pada dengue fever dan severe dengue

Sichilia, Lea (2021) Perbedaan ekspresi gen untuk proses netosis pada dengue fever dan severe dengue. Bachelor thesis, Universitas Pelita Harapan.

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Abstract

Latar Belakang: Infeksi dengue adalah infeksi virus yang ditularkan oleh nyamuk jenis Aedes aegypti dan Aedes albopictus. Dengue virus (DENV) adalah virus RNA yang merupakan anggota dari famili Flaviviridae dan genus Flavivirus dan memiliki 4 serotipe yaitu DENV-1. DENV-2. DENV-3, dan DENV-4. Infeksi dengue dapat diklasifikasikan menurut derajat keparahannya menjadi dengue fever (DF) dengan atau tanpa warning sign atau severe dengue (DHF/DSS). Adanya aktivasi neutrofil pada infeksi dengue telah dilaporkan sebelumnya. Akan tetapi, peranan salah satu mekanisme efektor neutrophil, NETosis, dalam patogenesis infeksi dengue belum banyak diketahui. Penelitian ini dilakukan untuk mengetahui perbedaan ekspresi gen-gen yang meregulasi NETosis pada dengue fever dan severe dengue. Metode: Jenis penelitian yang digunakan adalah penelitian analitik yang menggunakan pendekatan studi potong lintang (cross sectional). Jumlah sampel pada penelitian ini adalah 80 pasien dari Rumah Sakit Dong Thap, Vietnam yang terdiri dari 56 pasien dengan keadaan dengue fever dan 24 pasien dengan keadaan severe dengue Data yang telah terkumpul diolah menggunakan uji statistik dengan menggunakan SPSS (Stastistical Package for the Social Sciences) versi 25, Microsoft Excel 2019, dan Software GraphPad Prism. Hasil: Pada fase akut ditemukan nilai median ekspresi gen PADI4, MPO, ELANE yang lebih tinggi pada kelompok severe dengue dibandingkan dengue fever (PADI4: 12.91 vs. 12.73, p<0.05; MPO: 7.90 vs. 7.58, p<0.05; ELANE: 8.75 vs. 7.99, p<0.01). Walaupun tidak terdapat perbedaan ekspresi gen NOX2 pada fase akut, gen tersebut ditemukan secara signifikan lebih tinggi pada kelompok severe dengue dibandingkan dengue fever pada fase kritis (11 vs. 10.64, p<0.01). Ekspresi gen NETosis lainnya, PADI4, MPO, ELANE juga ditemukan lebih tinggi pada kelompok severe dengue dibandingkan kelompok dengue fever ( PADI4:12.83 vs. 12.15, p<0.001; MPO: 7.48 vs. 5.92, p<0.001; ELANE: 9.07 vs. 6.97 p<0.001). Kesimpulan: NETosis berperan dalam menentukan tingkat keparahan infeksi dengue, dimana aktivitas NETosis yang meningkat ditunjukkan melalui tingginya ekspresi gen-gen NETosis secara signifikan ditemukan pada keadaan severe dengue. /Background: Dengue infection is a viral infection transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Dengue virus (DENV) is an RNA virus which is a member of the Flaviviridae family and the Flavivirus genus and has 4 serotypes, namely DENV-1. DENV-2. DENV-3, and DENV-4. Dengue infection can be classified according to the degree of severity into dengue with or without a warning sign such as (DF) and also severe dengue (DHF / DSS). The activation of neutrophil during dengue infection has been reported previously. However, the role of neutrophil effector via NETosis in dengue infection pathogenesis remains unclear. Methods: This type of research is an analytical study using a cross-sectional study approach. The number of samples in this study were 80 patients from Dong Thap Hospital, Vietnam consisting of 56 patients with dengue fever and 24 patients with severe dengue fever. The data that has been collected is processed using statistical tests using SPSS (Statistical Package for Social Sciences) version 25, Microsoft Excel 2019, and GraphPad Prism Software. Results: In the acute phase, there was a higher median value of PADI4, MPO, ELANE gene expression in the severe dengue group compared to dengue fever (PADI4: 12.91 vs. 12.73, p <0.05; MPO: 7.90 vs. 7.58, p <0.05; ELANE: 8.75 vs. 7.99, p <0.01). Although there was no difference in NOX2 gene expression in the acute phase, this gene was found to be significantly higher in the severe dengue group compared to dengue fever in the critical phase (11 vs. 10.64, p <0.01). Expression of other NETosis genes, PADI4, MPO, ELANE were also found to be higher in the severe dengue group than in the dengue fever group (PADI4: 12.83 vs. 12.15, p <0.001; MPO: 7.48 vs. 5.92, p <0.001; ELANE: 9.07 vs. 6.97 p <0.001). Conclusion: NETosis plays a role in determining the severity of dengue infection, where the increased NETosis activity is indicated by the high expression of NETosis genes which is significantly found in severe dengue conditions.

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