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"ABSTRAKInfeksi oleh virus hepatitis B (VHB) dapat menjadi infeksi akut yang berakhir dengan resolusi infeksi ataupun berlanjut menjadi infeksi kronis. Resolusi infeksi dalam infeksi VHB ditandai dengan hilangnya hepatitis B surface antigen (HBsAg) dan keberadaan antibodi terhadap HBsAg (anti-HBs). Kemampuan sel B dalam mensintesis anti-HBs dipengaruhi oleh sel T helper 1 (Th1) ataupun T helper 2 (Th2). Sekresi sitokin yang terkoordinasi dari Th1 ataupun Th2 sangat dibutuhkan mengingat sitokin yang dihasilkan oleh kedua sel T helper (Th) tersebut memiliki peranan yang berbeda dan dapat bekerja secara antagonis. Penelitian ini bertujuan untuk mengetahui kemampuan pasien hepatitis B kronis dalam mensintesis anti-HBs dan membandingkan pola sintesis sitokin IL-10, IFN-gamma dan IL-2 dari pasien hepatitis B kronis dengan pasien yang mengalami resolusi infeksi. Pada penelitian ini sel mononuklear darah tepi manusia (SMDT) diambil dari 10 subjek pasien hepatitis B kronis, 10 subjek pasien yang mengalami resolusi infeksi dari hepatitis B dan 10 subjek individu sehat yang berhasil divaksinasi. SMDT dikultur dengan stimulan HBsAg rekombinan (rHBsAg) atau fitohemaglutinin (PHA) untuk sintesis sitokin dan pokeweed mitogen (PWM) untuk sintesis anti-HBs secara in vitro. Hasil dari penelitian ini ditemukan produksi anti-HBs secara in vitro dari 70% individu sehat yang berhasil divaksinasi dan 40% pasien hepatitis B yang mengalami resolusi infeksi, sementara pada pasien hepatitis B kronis tidak ditemukan hal tersebut. Pola sitokin IL-10, IFN-gamma dan IL-2 antara pasien hepatitis B yang mengalami resolusi infeksi dan pasien hepatitis B kronis tidak memiliki perbedaan yang bermakna. Akan tetapi, respons IFN-gamma terhadap rHBsAg pada pasien hepatitis B yang mengalami resolusi infeksi cenderung lebih kuat. Korelasi antara sitokin IL-10, IFN-gamma dan IL-2 dengan produksi anti-HBs secara in vitro tidak ditemukan pada kedua kelompok tersebut, sementara korelasi IL-2 dengan sintesis anti-HBs in vitro ditemukan pada individu yang divaksinasi. Penelitian ini menunjukkan SMDT dari pasien hepatitis B kronis tidak dapat mensintesis anti-HBs secara in vitro dan pada pasien tersebut tidak memiliki perbedaan pola sintesis sitokin IL-10, IFN-gamma dan IL-2 jika dibandingkan dengan pasien hepatitis B yang mengalami resolusi infeksi.

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ABSTRACTHepatitis B virus (HBV) infection can lead to acute self-limited infection or lead to chronic hepatitis B infection. Resolution of infection is marked by seroconversion of hepatitis B surface antigen (HBsAg) to antibody to HBsAg (anti-HBs) which also give protection to HBV reinfection. Anti-HBs is produced by B cells as response to HBsAg. B cells response to HBsAg is affected by cytokines from T helper 1 (Th1) and T helper 2 (Th2) cells. Coordinated cytokines secreted by Th1 or Th2 cells is necessary due to the fact that they could work antagonistically. Th1 cytokines, such as IFN-gamma, are known to induce cellular immune responses, while Th2 cytokines, such as IL-4, -5 and -10, are known to induce humoral immune responses. This study aimed to investigate the capability of chronic hepatitis B patients (CHB) to synthesize anti-HBs in vitro and to compare IL-10, IFN-gamma and IL-2 levels between CHB patientis with resolved hepatitis B (RHB) patients. In this study, peripheral blood mononuclear cells (PBMCs) were taken from 10 CHB patients, 10 RHB patients and 10 healthy hepatitis B vaccinated individuals. PBMCs were cultured in presence of recombinant HBsAg (rHBsAg) and PHA to cytokines synthesis and pokeweed mitogen (PWM) to anti-HBs synthesis in vitro. As results, synthesis of anti-HBs in vitro were found in PBMCs from 70% of healthy hepatitis B vaccinated individuals and 40% of RHB patients, while PBMCs from CHB patients could not. No significant differences were found in IL-10, IFN-gamma and IL-2 cytokine levels between CHB patients and RHB patients, although IFN-gamma responses to rHBsAg had a tendency to be stronger in RHB patients. Correlation between IL-10, IFN-gamma and IL-2 cytokine levels and anti-HBs synthesis in vitro was not found in CHB patients and RHB patients. Meanwhile, IL-2 and anti-HBs synthesis in vitro were correlated in healthy hepatitis B vaccinated individuals. In conclusion, this study showed that PBMCs from CHB patients were not capable in synthesizing anti-HBs in vitro and had no differences in IL-10, IFN-gamma and IL-2 cytokine levels with RHB patients."

"ABSTRAKKelapa sawit merupakan tanaman perkebunan yang banyak dibudidayakan di Indonesia, dengan luas sekitar 11 juta hektar pada tahun 2014. Serbuk sari kelapa sawit memiliki potensi alergi yang cukup besar, karena memiliki ukuran relatif kecil, berjumlah relatif banyak, dan bersifat anemofili.Penelitian ini bertujuan untuk mengetahui karakter kandidat protein alergen serbuk sari kelapa sawit melalui metode SDS-PAGE dan Western Blotting, serta mengetahui aktivitas IgA, IgE, IgG, IgM, dan IFN-γ pada sel Peripheral Blood Mononuclear Cell (PBMC) terhadap induksi protein serbuk sari kelapa sawit yang dilakukan secara in vitro. Penelitian diawali dengan ekstraksi protein serbuk sari kelapa sawit, yang berasal dari beberapa wilayah di Indonesia. Berat molekul protein dianalisis dengan metode SDS-PAGE, serta uji kealergenikan kandidat protein alergen diuji dengan menggunakan 21 serum pasien alergi melalui metode Western Blotting. Protein serbuk sari kelapa sawit juga diinduksikan pada kultur sel PBMC. Proses pendeteksian IgA, IgE, IgG, IgM, dan IFN-γ dilakukan menggunakan metode ELISA. Berat molekul protein serbuk sari kelapa sawit diketahui berukuran 10?80 kDa.Hasil uji kealergenikan protein tersebut pada Western Blotting menunjukkan kandidat protein alergen memiliki ukuran 14 kDa, 15 kDa, 20 kDa dan 31 kDa. Aktivitas beberapa immunoglobulin dan sitokin berhasil terdeteksi. Konsentrasi IgA didapatkan sebesar 0,022 pg/ml, IgE sebesar 9,655 pg/ml, IgG sebesar 39,856 pg/ml, IgM sebesar 10,369 pg/ml, dan IFN-γ sebesar 2.617,240 pg/ml.

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ABSTRACT

Oil palm is a plant that widely cultivated in Indonesia, with an area of about 11 million hectares in 2014. Oil palm pollen is potential to caused allergy, because it has a small size, much in amount, and was dispersed by wind.

This study aims to determine the character of the allergen protein candidate from oil palm pollen by using SDS-PAGE and Western Blotting, and also to know the activity of IgA, IgE, IgG, IgM, and IFN-γ against exposure to oil palm pollen protein performed in vitro on Peripheral Blood Mononuclear Cell (PBMC). The study begins with the protein extraction from oil palm pollen, which is derived from several regions in Indonesia. The molecular weight of these proteins are analyzed using SDS-PAGE. Allergenic test of allergen protein candidates were tested using 21 serum of allergic patients through Western Blotting method. Oil palm pollen protein also induced in PBMC cultures. The detection of IgA, IgE, IgG, IgM, and IFN-γ were performed using ELISA. The molecular weight of oil palm pollen protein is about 10?80 kDa.

Allergenic test results through Western Blotting showed the allergen protein candidates have a size of 14 kDa, 15 kDa, 20 kDa and 31 kDa. Immunoglobulin and cytokine activity successfully detected. The IgA concentrations obtained 0.022 pg/ml, IgE obtained 9.655 pg/ml, IgG obtained 39.856 pg/ml, IgM obtained 10.369 pg/ml, and IFN-γ obtained 2,617.240 pg /ml."

"Karsinoma hepatoseluler (KHS) adalah salah satu kanker dengan laju mortalitas tertinggi di dunia. Kadar serum alfa-fetoprotein (AFP) dapat digunakan sebagai biomarker untuk menegakkan diagnosis dini. Tetapi, perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus belum diketahui. Mengetahui perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus. Penelitian potong lintang dilakukan di RSUPN Cipto Mangunkusumo, Jakarta pada Januari-Oktober 2018 dengan melihat data rekam medis dari 287 pasien yang terdiagnosis KHS dalam periode 2013-2017. Nilai median (minimum-maksimum) dari kadar AFP pada pasien KHS dengan etiologi infeksi VHB atau VHC adalah 419 (0.8-400.000). Nilai median (minimum-maksimum) kadar AFP pada pasien KHS dengan etiologi non infeksi VHB-VHC adalah 7.18 (0.6-90.944). Terdapat perbedaan bermakna antara kadar AFP dengan KHS dengan etiologi infeksi VHB atau VHC dan etiologi non infeksi VHB-VHC.

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Hepatocellular carcinoma (HCC) is one of the highest rates of mortality in the world. Serum alpha-fetoprotein (AFP) levels can be used as a biomarker for early diagnosis. However, the comparison between serum AFP and HCC with viral infections etiology and non-viral etiology is unknown. This research aims to determine the comparison between serum AFP and HCC with viral infections etiology and non-viral aetiology. A cross-sectional study conducted in Cipto Mangunkusumo Hospital, Jakarta in January to October 2018 by reviewing 287 medical records of patients diagnosed with HCC from 2013-2017 period of time. The median (minimum-maximum) value of AFP levels in HCC patients with the etiology of HBV or HCV infection is 419 (0.8-400,000). The median value (minimum-maximum) of AFP levels in HCC patients with the etiology of non HBV-HCV infection was 7.18 (0.6-90,944). There were significant differences between AFP levels and KHS with the etiology of HBV or HCV infections and the etiology of non HBV-HCV infections."

"Latar Belakang: Mutasi Al762T/GI764A basal core promoter (BCP) dan Gl896A precore pada genom virus hepatitis B (VHB) berhubungan dengan tingkat keparahan penyakit hati, namun demikian peran mutasi-mutasi tersebut pada perjalanan infeksi hepatitis B kronis masih belum jelas. Olch karena itu, penelitian ini bertujuan untuk mengetahui prevalensi mutasi Al762T/Gl764A dan Gl896A serta hubungannya dengan fase-fase pada perjalanan infeksi hepatitis B kronis. Metodologi: Seratus empat puluh pasien hepatitis B kronis yang dilibatkan dalam pcnelitian ini, belum mendapatkan pengobatan, dan dikelompokkan ke dalam fase immunotolerant (IT), immunoclearance (IC), non/Iow replicative (LR) dan hepatitis "c" negatif (ENH). DNA VHB diperiksa dan diul-cur kadarnya dengan teknik polymerase chain reaction, kemudian disekuensing untuk dianalisis. Hasil: Usia subjek lebih tua pada kelompok ENH dan LR dibandingkan dengan fase lain (p<0.05). Kadar DNA paling tinggi pada fase IC dan paling rendah pada fase LR (p<0.00l), sementara pria mempunyai risiko lebih besar terjadi reaktivasi dengan HBeAg negatif (p<0.05). Mutasi Al 762T/GI764A tidak berbeda bermakna pada semua fase (p=0.56) dan lebih tinggi pada genotipe C dan subtipe adr (p<0.05). Mutasi Gl896A paling tinggi pada Pass LR (p<0.05), dan tidak berbeda bcrmakna pada genotipe dan subtipe VHB. Tidak ada hubungan antara kadar DNA V1-IB dengan mutasi di prccore dan BCP. Kesimpulan: Prevalensi mutasi Gl896A berbeda pada fase hepatitis B kronis di Indonesia, ditemukan lebih sering pada usia lebih tua dan fase lanjut. Mutasi A1762T/Gl764A berkorelasi dengan genotipe dan subtipe VHB, sebaliknya tidak berhubungan dengan fase infeksi. Studi ini mengindikasikan bahwa mutasi BCP tidak berhubungan dcngan serokonversi HBeAg pada perjalanan infeksi hepatitis B kronis.

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Background: Precore Gl896A and basal core promoter (BCP) A1762T/G1764A mutations of hepatitis B virus (HBV) genome have been correlated with severe liver diseases; however, their role in the pathogenesis of chronic hepatitis B (CHB) remains unclear. We assessed the prevalence and association of these mutations in different phases of CHB in Indonesian patients.

Methods: One-hundred and forty CHB patients, not undergoing antiviral therapy, were classified into immune-tolerance (IT), immune-clearance (IC), nonllow- replicative (LR), and hepatitis B e antigen (HBeAg)-negative hepatitis (ENH) phases. HBV DNA was detected and quantified by polymerase chain reaction then analyzed by sequencing.

Results: ENH and LR patients were older than IC or IT patients (p <0.05). HBV DNA levels were highest in IC patients and lowest in LR (p<0.0001). The A1896 pre-core mutants were most prevalent in LR (p<0.00l) and higher in ENH (p<0.00I) than in IT and IC patients, while the Al762T/Gl764A BCP mutants were comparable between all phases. The Al762T/Gl764A BCP mutants were more frequently identified in genotype C than in genotype B (p <0.05), and in subtype adr than in subtypes adw and ayw (p <0.05). The Tl858 mutants were detected in almost all HBV isolates regardless the genotypes (B and C). N0 associations were observed between HBV DNA levels and precore as well as BCP mutations.

Conclusions: The prevalence of precore A1896 mutation differed in phases of CHB in Indonesian patients with preponderance in older ages and later stages. BCP AI762T/Gl764A mutations were associated with HBV genotypes and subtypes, itrespective of infection phases. These findings indicate that BCP mutations could be independent of HBeAg seroconversion in the natural history of chronic HBV infection."

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Peran Th17 dalam keganasan, khususnya karsinoma sel hati, masih menjadi perdebatan. Sel Th17, sel penghasil IL-17, dilaporkan berhubungan dengan efek protumor dan antitumor sekaligus. Di lain sisi, sel Th1 yang menyekresikan IFN-γ memiliki sifat antitumor. Kemoembolisasi transarterial / transarterial chemo-embolization (TACE) diketahui dapat menyebabkan nekrosis tumor, namun peran TACE dalam memengaruhi sel Th17, Th1, IL-17, IFN-γ, dan rasio neutrofil limfosit (RNL) masih belum diketahui. Penelitian ini bertujuan untuk menentukan perubahan Th17, Th1, IL-17, IFN-γ, dan nilai RNL pada pasien KSH yang menjalani TACE.

Penelitian ini dilakukan sepanjang Juni 2015–Januari 2019 di RSCM dan beberapa rumah sakit jejaring di Jakarta. Desain potong lintang digunakan untuk membandingkan respons imun pasien KSH dengan sirosis hati. Desain kohort prospektif diterapkan untuk menilai hubungan respons imun dengan keberhasilan TACE. Pengambilan darah dilakukan sebelum dan 30 hari setelah tindakan TACE pada pasien KSH dan satu kali pada pasien sirosis. Nilai Th17 dan Th1 dianalisis menggunakan teknik flowcytometry, sedangkan nilai IL-17 dan IFN-γ diukur dengan teknik enzyme-linked immunosorbent assay (ELISA). Nilai RNL dihitung dari pembagian kadar neutrofil dengan limfosit yang diperoleh dari pemeriksaan hitung jenis. Respons terhadap TACE dievaluasi berdasarkan kriteria mRECIST.

Sebanyak 40 pasien sirosis dan 41 pasien KSH berpartisipasi dalam penelitian ini. Sebanyak 12 pasien dan 29 pasien termasuk ke dalam kelompok respons dan nonrespons, secara berurutan. Penurunan kadar AFP dan ukuran tumor secara bermakna ditemukan pada kelompok respons. Pada kelompok ini, juga ditemukan peningkatan bermakna kadar Th1, Th17, dan sel T CD4+/IFN-γ+/IL-17+ setelah TACE. Nilai IL-17, IFN-γ, dan RNL tidak berhubungan dengan respons TACE. Di samping itu, didapatkan peningkatan bermakna kadar CD4+/IFN-γ+/IL-17- pada kelompok nonrespons.

Simpulan: Peningkatan kadar Th1 dan Th17 dalam darah perifer yang diiringi dengan peningkatan sel T CD4+/IFN-γ+/IL-17+ didapatkan pada pasien KSH yang berespons baik terhadap TACE.

 

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The role of Th17 cells in malignancy, especially hepatocellular carcinoma, remains controversial. Th17 cells, IL-17 producing cells, were reported to be associated with both protumor and antitumor effects. On the other hand, Th1 cells, IFN-γ producing cells, had antitumor properties. Transarterial chemoembolization (TACE) is known for its potency to cause tumor necrosis, but its impact on Th17, Th1, IL-17, IFN-γ, and neutrophil-to-lymphocyte ratio (NLR) is still unclear. This study aims to determine the changes in Th17, Th1, IL-17, IFN-γ, and NLR levels in HCC patients treated with TACE.

This study was conducted from June 2015 to January 2019 at Cipto Mangunkusumo National General Hospital dan several affiliated hospitals in Jakarta. A cross-sectional study design was used to compare the immune response between HCC and liver cirrhotic patients. A prospective cohort study design was applied to assess the relationship between immune response and tumor response to TACE. Plasma sampling was obtained from HCC and cirrhotic patients that fulfilled the inclusion and exclusion criteria. Blood samples were collected immediately before and 30 days after TACE. Th17 and Th1 levels were measured using flowcytometry technique, while IL-17 and IFN-γ levels were quantified by using enzyme-linked immunosorbent assay (ELISA). The value of NLR was calculated by dividing the neutrophil count by the lymphocyte count. Responses to TACE were evaluated based on mRECIST.

A total of 40 cirrhotic and 41 HCC patients participated in this study. As many as 12 and 29 patients were included in the response and nonresponse group, respectively. In the response group, there were significant reduction of AFP levels and tumor size, as well as significant increase of Th1, Th17 and CD4+/IFN-γ+/IL-17+ T cells levels after TACE. Furthermore, there was an increase of CD4+/IFN-γ+/IL-17- levels in the non-response group. The values of IL-17, IFN-γ, and NLR were not related to TACE response.

Conclusion: Patients with good response to TACE had increased levels of circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells.

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"Vaksinasi merupakan upaya kesehatan preventif terhadap penularan penyakit infeksi, terutama oleh bakteri dan virus. Vaksin hepatitis B yang tersedia di pasar berbentuk suspensi cair yang sensitif terhadap panas. Penelitian dilakukan untuk menghasilkan formula vaksin hepatitis B yang dapat dikelola di luar sistem rantai dingin. Optimisasi pada alat pengering menunjukkan bahwa formula vaksin cair dapat dikeringkan dan dimonitor untuk menghasilkan serbuk vaksin yang berkualitas. Teknik pengeringan yang digunakan meliputi : spray drying, freeze drying dan vacuum drying. Formula vaksin yang disiapkan sebanyak 6 sampel dengan kode A sampai F yang merefleksikan komposisi bahan pengisi dan teknik pengeringan. Serbuk vaksin dikarakterisasi secara fisik, kimia dan potensi antigenik serta dilakukan uji stabilitas dipercepat.Hasil penelitian menunjukkan bahwa teknik pengeringan berpengaruh terhadap penurunan pH dan potensi antigenik vaksin. Kombinasi trehalosa dan mannitol tidak memberikan perbedaan yang signifikan terhadap pH dan potensi relatif vaksin kering. Vaksin yang dikeringkan secara freeze drying dengan komposisi trehalosa: mannitol 7:3 menunjukkan potensi relatif secara in vitro sebesar 97,78 dan in vivo 35,6 serta berpotensi untuk dikelola di luar sistem rantai dingin.

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Vaccination is a preventive health measure against the transmission of infectious diseases, especially by bacteria and viruses. Hepatitis B vaccines are available in the market in the form of liquid suspensions that is heat sensitive. The study was conducted to produce the hepatitis B vaccine formula which can be managed out of the cold chain system. Optimization of the drying instrument indicates that liquid vaccine formula can be dried and monitored to produce quality vaccines powder. Drying techniques used include spray drying, freeze drying and vacuum drying. Vaccine formulas were prepared as much as 6 samples with codes A through F, which reflects the composition of fillers and drying techniques. The powder vaccine was characterized by physical, chemical and antigenic potential as well as an accelerated stability test.

The results showed that the drying technique affecting the decrease of pH and the potential of antigenic vaccine. The combination of trehalose and mannitol did not provide a significant difference to the pH and the relative potency of dried vaccine. The vaccine which was dried by freeze drying with the composition of trehalose mannitol 7 3 showed the relative potency in vitro at 97,78 and in vivo at 35,6 and has an opportunity to be managed out of the cold chain system."

"Diabetes melitus (DM) tipe 2 adalah penyakit yang berhubungan dengan kondisi inflamasi ringan kronis. Selain terjadi peningkatan kadar sitokin proinflamasi, diduga terjadi gangguan pada mediator antiinflamasi, yaitu enzim indoleamine 2,3-dioxygenase (IDO). Tujuan dari penelitian ini adalah menganalisis produksi IDO dari kultur peripheral blood mononuclear cells (PBMC) pada penderita DM tipe 2 dan meneliti hubungan IDO dengan kadar sitokin proinflamasi seperti TNF-α, IL-6, dan IFN-γ; serta sitokin antiinflamasi, IL-10. Sampel PBMC diambil dari 21 pasien DM tipe 2 dan 17 subjek kontrol sehat kemudian dilakukan kultur dengan stimulasi phytohemagglutinin (PHA). Setelah kultur selama 3 hari, produksi TNF-α, IL-6, IFN-γ, dan IL-10 diukur menggunakan multiplex immunoassay, sedangkan kadar IDO diukur menggunakan ELISA. Kadar IDO dari kultur PBMC tanpa stimulasi dan dengan stimulasi PHA secara signifikan lebih tinggi pada pasien DM tipe 2 dengan p<0,001 dan p=0,012. Sebanyak 52,8% pasien DM tipe 2 mengalami penurunan produksi IDO setelah distimulasi PHA dan hal tersebut berhubungan dengan kadar IFN-γ yang rendah dengan p=0,005. Di lain pihak, 42,8% pasien DM tipe 2 mengalami peningkatan produksi IDO setelah stimulasi PHA dan hal ini berhubungan dengan rasio TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) dan IFN-γ/IL-10 (r=0,422 p=0,129). Pada DM tipe 2, terjadi perubahan produksi IDO. IFN-γ yang rendah berkontribusi pada penurunan produksi IDO. Sementara itu, respon proinflamasi berhubungan dengan peningkatan produksi IDO.

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Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammatory condition. Besides the increased of proinflammatory cytokines level, it was found that anti-inflammatory mediators were disturbed. So, we would analyse the production of indoleamine 2,3-dioxygenase (IDO) in PHA-stimulated PBMC from type 2 DM patients and investigate its association to pro and anti-inflammatory cytokines. PBMC samples were collected from 21 patients with T2DM and 17 healthy subjects, then followed by 3-day PHA stimulation. In vitro production of TNF-α, IL-6, IFN-γ and IL-10 were measured using multiplex immunoassay; meanwhile, IDO level was assessed using ELISA. IDO concentration from unstimulated and PHA-stimulated PBMC were significantly higher in T2DM patients with p<0,001 and p=0.012 respectively. Reduced IDO production occurred in 52,8% of T2DM and it was associated with low interferon γ with p=0.005; whereas 42,8% of T2DM had higher IDO production and had moderate positive correlations with ratio of TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) and IFN-γ/IL-10 (r=0,422 p=0,129). We could conclude that there is an alteration of IDO production after PHA stimulation in T2DM. Low interferon γ level seems to contribute in reducing IDO production. In T2DM with higher IDO production, proinflammatory responses are more influential in increasing IDO production."