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"Latar belakang. Pada penyakit graves (GD), konsentrasi vitamin D berbanding terbalik dengan titer antibodi dan berbanding lurus dengan status remisi. Pembentukan autoantibodi diawali dari pajanan self antigen oleh sel dendritik (DC), sebagai antigen presenting cell (APC), ke sel T naif. Kemampuan DC sebagai APC ditentukan oleh tingkat kematangannya. Sel dendritik, APC utama pada GD, bersifat lebih aktif dalam respons imun dibandingkan dengan subjek sehat. Studi pada SLE, MS, dan penyakit crohn menunjukkan efek imunoregulator vitamin D terutama melalui hambatan pematangan DC sehingga fungsi imunogenitasnya berkurang.Tujuan. Mengetahui efek 1,25-D3 in vitro dan 1α-D3 in vivo terhadap pematangan DC pasien GDMetode. Pada periode Mei 2014 sampai dengan Maret 2015 dilakukan studi eksperimental dan klinis, masing-masing pada 12 dan 25 pasien GD fase hipertiroid. Pada studi eksperimental, dilakukan kultur monocyte derived dendritic cell (MDDC) pasien GD dengan atau tanpa intervensi 1,25-D3 in vitro pada tahap monosit dan maturasi distimulasi dengan lipopolysaccharide (LPS). Pada studi klinis, sebanyak 12 dan 13 pasien GD, masing-masing mendapatkan 1α-D3 dan plasebo selama 8 minggu, di samping mendapatkan terapi standar PTU 100 mg 3 kali sehari. Kultur MDDC dilakukan sebelum dan sesudah suplementasi dan dilakukan perbandingan pematangan DC sebelum dan sesudah suplementasi pada kedua kelompok. Pematangan DC dilihat dari ekspresi penanda DC (HLA-DR, CD80, CD40, CD83, CD14, dan CD206) dan rasio sitokin IL-12/IL-10 pada supernatan kultur.Hasil. Pada studi in vitro, pascastimulasi LPS, DC yang dikultur dengan 1,25-D3 menunjukkan ekspresi HLA-DR, CD80, CD40, dan CD83 lebih rendah serta ekspresi CD14 dan CD206 yang lebih tinggi dibandingkan dengan DC yang dikultur dengan LPS saja. Pada DC yang dikultur dengan 1,25-D3, didapatkan rasio IL-12/IL-10 lebih rendah daripada DC tanpa 1,25-D3. Pada studi klinis, apabila dibandingkan antara ekspresi penanda DC serta rasio IL-12/IL-10 sebelum dan sesudah suplementasi 1α-D3 selama 8 minggu, belum didapatkan perbedaan yang bermakna pada ekspresi penanda DC dan rasio sitokin IL-12/IL-10.Simpulan. Pemberian 1,25-D3 in vitro menghambat pematangan DC pasien GD, sedangkan efek pemberian 1α-D3 in vivo terhadap pematangan DC belum dapat ditunjukkan pada penelitian ini.

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Background. In graves? disease (GD), vitamin D levels is inversely proportional to antibody titer and proportionally associated with remission status. The development of autoantibody is initiated by self-antigen exposure by dendritic cells (DC) as the antigen presenting cells (APC) to the naïve T cells. The ability of DC as APC is determined by its maturity level. Dendritic cells, the major APC in GD, have more active immune responses than those in healthy subjects. Studies on systemic lupus erythematosus (SLE), multiple sclerosis (MS) and crohn?s disease have demonstrated immunoregulator effects of vitamin D, mainly through inhibition of DC maturation, which may lead to lower immunogenic function.

Aim. To identify the effect of 1,25-D3 in vitro and 1α-D3 in vivo on DC maturation in patients with GD.

Method. Our study consisted of an experimental and a clinical study started from May 2014 until March 2015, which was conducted in 12 and 25 GD patients with thyrotoxicosis, respectively. In the experimental study, cultures of monocyte derived dendritic cell (MDDC) of GD patients were performed, with or without intervention of 1,25-D3 in vitro at monocytic phase and the maturation was stimulated by lipopolysaccharide (LPS). In the clinical study, there were 12 GD patients who received 1α-D3 supplementation and 13 GD patients who received placebo for 8 weeks, in addition to the standard treatment of PTU 100 mg three times a day. MDDC cultures and comparison of DC maturation were performed before and after the supplementation for both groups. DC maturation was evaluated based on the expression of DC markers (HLA-DR, CD80, CD40, CD83, CD14 and CD206) and the ratio of cytokines IL-12/IL-10 levels in the culture supernatants.

Results. In the in vitro study and following the LPS stimulation, DC cells cultured with 1,25-D3 showed lower expression of HLA-DR, CD80, CD40 and CD83 and higher expression of CD14 and CD206 compared to DC cultured with LPS alone. DC, which were cultured with 1,25-D3 had lower ratio of IL-12/IL-10 levels than those cultured without 1,25-D3. In the clinical study, when the expression of DC marker as well as the ratio of IL-12/IL-10 levels between before and after the 8-week supplementation of 1α-D3 were compared, we found no significant difference on the expression of DC markers and the ratio of IL-12/IL10.

Conclusion. In vitro 1,25-D3 supplementation inhibits DC maturation in patients with GD; while the effects of in vivo 1α-D3 treatment on DC maturation have not been clearly demonstrated in the present study yet."

"Latar Belakang. SNP IL-28B mempunyai peran penting dalam pencapaian SVR pada pengobatan Hepatitis C kronik antarras manusia dan berpotensi untuk memprediksi keberhasilan terapi Peg-IFN/RBV maupun penyembuhan spontan Hepatitis C akut. Hingga saat ini, mekanisme molekular yang mendasari kaitan SNP IL-28B dengan respons terapi masih belum jelas meskipun diperkirakan terkait dengan ekspresi IFN-l3 dan reseptor IFN-l3 di jaringan hati. Tujuan. Mengetahui hubungan SNP IL-28B dan SVR serta ekspresi IFN-l3 dan reseptor IFN-l3 di jaringan hati serta mendapatkan kemaknaan klinis SNP IL-28B dan kovariat SVR dalam memprediksi respons terapi Peg-IFN/RBV. Metode. Penelitian ini terbagi menjadi dua bagian. Pertama, penelitian potong lintang pada pasien Hepatitis C kronik yang telah selesai menjalani terapi Peg-IFN/RBV dengan melakukan pengambilan data dasar dan sampel darah. Kedua, penelitian kasus kontrol pasien yang menjalani biopsi hati dan pewarnaan imunohistokimia. Hasil. Pencapaian SVR yang lebih tinggi ditemukan pada pasien dengan alel CC SNP IL28B (p=0,014). Alel CC SNP IL28B mempunyai ekspresi IFN-l3 lebih tinggi dibandingkan dengan alel non-CC (p = 0,018). Meskipun demikian, tidak ditemukan adanya perbedaan bermakna antara ekspresi IFN-l3 (p = 0,237) maupun reseptor IFN-l3 dengan SVR (p = 0,237). Pada penelitian ini, diformulasikan persamaan faktor risiko pencapaian SVR sebagai p = 1 / (1 + e-y); e = 2,7, y = -2,498 + 2,652 (SNP IL-28B) + 2,029 (trombosit) untuk praterapi dan sedangkan untuk masa terapi y = -0,223 + 2,621 (RVR). Simpulan. SNP IL-28B merupakan faktor risiko praterapi yang penting dalam pengobatan hep C kronik G1 menggunakan terapi dua kombinasi. Alel mayor IL28B mengekspresikan IFN-l3 dan reseptornya lebih banyak sebagai respons adanya VHC, namun tidak ditemukan adanya hubungan hal tersebut dengan pencapaian SVR. RVR merupakan faktor masa terapi terbaik untuk memprediksi SVR. Penelitian lanjutan diperlukan untuk membuktikan adanya faktor lain yang berperan dalam pencapaian SVR.

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Background: SNP IL-28B played an important role in achieving sustained virological response (SVR) among different ethnics in chronic Hepatitis C patients and is considered potential in predicting treatment response of Pegylated interferon/ribavirin (Peg-IFN/RBV) combination and spontaneous clearance in acute hepatitis. Up to date, molecular mechanism underlying correlation between SNP IL28B and SVR has not been fully understood yet although it is predicted to be related to IFN-λ3 and IFN-λ3 receptor in liver tissues.

Aim: Understanding the association between SNP IL-28B and SVR in chronic Hepatitis C treatment and expression of IFN-l3 and IFN-l3 receptor in liver tissues to evaluate clinical importance of SNP IL-28B examination in Hepatitis C treatment of Peg-IFN/RBV through SVR prediction model.

Methods: This study consisted of two parts. First, a cross-sectional study on chronic Hepatitis C patients who completed Peg-IFN/RBV therapy. The second part was case control study on patients underwent liver biopsy and immunohistochemical staining.

Results: Sustained virological response was significantly higher in CC allele of SNP IL-28B compared to non CC allele (p = 0.015). Higher expression of IFN-l3 was found in CC allele compared to non CC allele (p = 0.018). On the other hand, there is no significant difference between SVR and expression of IFN-l3 (p = 0.237) and IFN-l3 receptor (p = 0.237). Risk factor for SVR probability were formulated into p = 1 / (1 + e-y); e = 2.7, y = -2.498 + 2.652 (SNP IL-28B) + 2.029 (thrombocytes) for pretreatment while for on treatment risk factor y = -0.223 + 2.621 (RVR)

Conclusion: SNP IL-28B was important pretreatment risk factor in genotype 1 chronic Hepatitis C treated with dual therapy. Major allele of IL-28B expressed more IFN-l3 and its receptor in response to HCV although no association between both factors was found. RVR was the best on treatment factor for SVR. Further evaluation study was required to find other possible factors affecting SVR achievement."

"[Association between SNP IL-28B and Sustained Virological Response and Its Relation with Expression of Interferon Lambda-3 and Interferon Lambda-3 Receptor in Liver Tissues of Chronic Hepatitis C Patients Treated with Pegylated Interferon α2 and Ribavirin;Association between SNP IL-28B and Sustained Virological Response and Its Relation with Expression of Interferon Lambda-3 and Interferon Lambda-3 Receptor in Liver Tissues of Chronic Hepatitis C Patients Treated with Pegylated Interferon α2 and Ribavirin, Association between SNP IL-28B and Sustained Virological Response and Its Relation with Expression of Interferon Lambda-3 and Interferon Lambda-3 Receptor in Liver Tissues of Chronic Hepatitis C Patients Treated with Pegylated Interferon α2 and Ribavirin]"

"Latar belakang. Meningkatnya kasus HIV-AIDS human immunodeficiency virus-acquired immunodeficiency syndrome secara global memicu kewaspadaan akan peningkatan infeksi oportunistik, salah satunya infeksi Pneumocystis jirovecii yang mengakibatkan pneumonia PjP. Infeksi PjP merupakan kasus yang sulit ditangani terkait rendahnya sensitivitas uji diagnostik diiringi dengan peningkatan kasus resistensi terhadap antibiotik. Di Indonesia belum terdapat data demografis, epidemiologi molekuler maupun data resistensi mengenai kasus infeksi PjP. Mengantisipasi masalah tersebut, dalam penelitian ini dikembangkan uji diagnostik PjP pada ODHA Orang Dengan HIV-AIDS terduga pneumonia melalui pendekatan molekular terhadap gen MSG Major Surface Glycoprotein disertai dengan karakterisasi gen DHPS dihidropteroat sintase dan gen mtLSU mitochondrial large subunit yang berkorelasi dengan genotipe resisten dan virulensi P. jirovecii. Tujuan penelitian. Memperoleh suatu uji deteksi infeksi PjP, data genotipe resistensi dan virulensi PjP melalui pendekatan secara molekuler yang dapat dimanfaatkan sebagai dasar data demografi dan epidemiologi molekuler PjP di Indonesia. Metode penelitian. Pengembangan uji diagnosis molekuler PjP terhadap gen MSG dilakukan dengan metode real- time PCR yang diujikan terhadap 100 sampel sputum. Pola genotipe resistensi dilakukan melalui amplifikasi gen DHPS dilanjutkan dengan restriction fragment length polymorphism RFLP . Virulensi daerah hot spot gen mtLSU dianalisis dengan metode PCR dan sekuensing DNA. Hasil. Secara demografi, diketahui prevalensi PjP pada ODHA terduga pneumonia di Jakarta mencapai 20,0, laki-laki 75, rentang usia terbanyak 31-40 tahun 35, dominan 80 pada kisaran sel limfosit T CD4 200-349 sel/L. Sebanyak 12 pasien menunjukkan gen DHPS positif, lima pasien 41,66 merupakan genotipe wild type WT dan 7 pasien lainnya 58,32 merupakan genotipe resisten, terdiri dari 16,67 genotipe-3 dan 41,66 genotipe campuran WT dan genotipe 1. Analisis virulensi berdasarkan gen mtLSU diperoleh 30 strain PjP positif yang didominasi oleh variasi-3. Status imun pasien lebih berkaitan dengan genotipe resistensi dibandingkan dengan jenis varian. Kesimpulan. Uji real-time PCR yang dikembangkan mampu memberikan nilai diagnostik yang lebih baik dibandingkan pewarnaan Giemsa. Terdapat 3 genotipe gen resistensi WT, genotipe 1 dan 3 dan 7 varian P. jirovecii yang bersirkulasi di Jakarta. Genotipe resistensi lebih berkaitan terhadap kondisi klinis pasien dibandingkan dengan jenis varian.

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Background. The global rise of HIV-AIDS cases increase the alertness against oportunistic infections, one of them is Pneumocystic jirovecii pneumonia PjP. PjP infection is a one of a tough infection to be cured due to low sensitivity of its diagnostic method following the escalation of PjP resistance against antibiotics. There is no demografic, molecular epidemiology nor antibiotics resistance data were available related to PjP infection in Indonesia. Thus, this study was conducted to develop a molecular test to diagnose PjP infection in HIV-AIDS suspected pneumonia patients based on MSG Major Surface Glycoprotein gene detection, followed by characterization of DHPS dihydropteroat syinthetase and mtLSU mitochondrial large subunit genes represent genoype resistance and P. jirovecii virulence. Research objective. To obtain a molecular test in diagnosing PjP infection and information of P. jirovecii genotype resistance and virulence based on molecular characteristics, which can be used further as demographic and molecular epidemiology basis data of PjP in Indonesia. Research methods. Molecular diagnostic test aimed for MSG gene of P. jirovecii detection was done through real-time PCR against 100 sputum samples. Genotype resistance and P. jirovecii polymorphism patterns was done through DHPS and mtLSU genes amplification followed by restriction fragment length polymorphism RFLP and DNA sequencing analysis. Virulence of the hot spot area are of the mtLSU gene was analyzed by PCR method and DNA sequencing. Results. The prevalence of PjP infection in HIV-AIDS suspected pneumonia patients in Jakarta was 20.0, male 75 within 31-40 y.o 35, dominant 80 from patients with CD4 T-lymphocytes of 200-349 cells/L. Molecular real-time PCR methods give five times sensitivity higher than Giemsa stain. Twelve patients showed positive DHPS gene, five patients 41.67 were wild type WT genotypes and 7 other patients 58.32 were resistant genotypes, with 16.66 was genotype-3 and other 41.66 was mixed genotypes WT and genotype 1. Virulence analysis based on mtLSU gene show 30 positive strains which dominated by variant-3. The patients immune status is more related to the resistance genotype compared to the variant type. Conclusion. The developed real-time PCR method is proven to able to give better diagnostic value than Giemsa stain. There are 3 genotypes of resistance genes WT, genotypes 1 and 3 and 7 variants of P. jirovecii circulating in Jakarta. Resistance genotypes are more related to the clinical condition of patients compared to variant types. "

"HIV coinfection in HCV-infected patients accelerates the course of disease and affects the outcome of Peg-IFN/RBV combination treatment. HCV-HIV coinfected patients are suspected to have HCV mutation in NS5A-ISDR/PKR-BD region that had a role to the successfulness of Peg-IFN/RBV therapy. SNP IL-28B polymorphism is predicted to have an effect on the HCV quasi-species evolution. However, until now the effect of HCV NS5A mutation and SNP IL-28B of the host to the response of treatment is still unclear.This study aimed to determine the presence and role of HCV NS5A-ISDR/PKR-BD region mutation and host SNP IL-28B on the succes of Peg-IFN/RBV combination treatment in HCV-HIV coinfected patients.Prospective cohort study design was conducted in this study. Plasma sample was collected from 22 monoinfected and 134 HCV-HIV coinfected patients prior to therapy. All of them were treated with Peg-IFN/RBV for 48 weeks. The examination of HCV RNA was performed 24 weeks after the end of therapy. PCR nucleotide sequencing was performed after the RNA virus extraction and cDNA synthesis had been performed. Analysis of secondary structure and prediction of mutation function were assessed by PredictProtein (PP) program.Sixteen from thirthy HCV-HIV co-infection patients and none from eight HCV patients achieved SVR. Nonneutral mutation ≥ 1 was found in 23/30 subjects with HCV-HIV co-infection. The presence of nonneutral mutation ≥ 1 was observed more frequent in SVR group than non-SVR group. Nonneutral mutation ≥ 1 was associated with SVR achievement, regardless the monoinfection or coinfection status (p = 0.04). Interaction of CC gene and nonneutral mutation was not associated with SVR. Secondary structure transformation of VHC NS5A was not associated with SVR in coinfected subjects. NS5A binding site structure was different from consensus in SVR group, while the structure was similar to consensus in non-SVR group.Nonneutral mutation ≥ 1 has the most important role on the SVR achievement in patients treated with Peg-IFN/RBV. The interaction of CC-gene and nonneutral mutation was not associated with SVR. The change of secondary structure was also not associated with SVR achievement, however, the changes of NS5A binding site structure were found in HCV-HIV coinfected patients who achieved SVR.

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Koinfeksi HIV pada pasien dengan infeksi VHC dapat memperberat perjalanan penyakit dan memengaruhi keberhasilan terapi kombinasi Peg-IFN/RBV. Pasien koinfeksi VHC-HIV diduga mengalami mutasi VHC pada regio NS5A-ISDR/PKR-BD yang mempunyai peran terhadap keberhasilan terapi Peg-IFN/RBV. Polimorfisme SNP IL-28B diprediksi berpengaruh terhadap evolusi quasi-spesies VHC, namun hingga saat ini keberadaan dan peran mutasi VHC NS5A serta SNP IL-28B pejamu pada koinfeksi VHC-HIV terhadap keberhasilan terapi masih belum diketahui secara jelas.Penelitian ini bertujuan untuk mengetahui keberadaan dan peran mutasi VHC NS5A-ISDR/PKR-BD serta SNP IL-28B pejamu terhadap keberhasilan terapi dengan kombinasi Peg-IFN/RBV pada pasien koinfeksi VHC-HIV.Penelitian ini menggunakan desain studi kohort prospektif. Sampel plasma dikumpulkan dari 22 subjek monoinfeksi dan 134 subjek koinfeksi sebelum menjalani terapi. Seluruh pasien mendapatkan terapi Peg-IFN/RBV selama 48 minggu. Pemeriksaan VHC RNA setelah 24 minggu dari akhir terapi dilakukan untuk menilai respons terapi (sustained virological response/SVR 24). Sekuensing nukleotida menggunakan PCR dilakukan setelah ekstraksi RNA virus dan sintesis cDNA dari sampel plasma. Analisis struktur sekunder dan prediksi fungsi mutasi menggunakan program PredictProtein (PP).Sebanyak 16 pasien dari 30 pasien koinfeksi VHC-HIV yang mengalami SVR serta tidak ada dari 8 pasien monoinfeksi VHC yang mengalami SVR. Mutasi nonnetral ≥ 1 ditemukan pada 23/30 pasien koinfeksi VHC-HIV. Keberadaan mutasi nonnetral ≥ 1 didapatkan lebih tinggi pada kelompok SVR (14 pasien) dibandingkan dengan non-SVR (9 pasien). Mutasi nonnetral ≥1 berhubungan dengan kejadian SVR, tanpa memandang status monoinfeksi dan koinfeksi (p = 0,04). Interaksi antara gen CC dan mutasi nonnetral tidak berhubungan dengan SVR. Perubahan struktur sekunder NS5A tidak berhubungan dengan SVR pada pasien koinfeksi. Struktur binding site NS5A pada kelompok SVR didapatkan berbeda dengan konsensus, sedangkan pada kelompok non-SVR mirip dengan konsensus.Mutasi nonnetral ≥ 1 berperan terhadap kejadian SVR pada pasien yang mendapat terapi Peg-IFN/RBV. Interaksi mutasi nonnetral dan gen CC tidak berhubungan dengan pencapaian SVR. Perubahan struktur sekunder juga tidak berhubungan dengan pencapaian SVR, akan tetapi perubahan struktur binding site NS5A-ISDR/PKR-BD ditemukan pada pasien koinfeksi VHC-HIV yang mencapai SVR dengan terapi Peg-IFN/RBV."