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"Artritis reumatoid AR adalah penyakit autoimun yang saat ini telah diketahui menunjukkan manifestasi klinis bukan hanya intraartikular, tetapi juga ekstraartikular. Kejadian kardiovaskular baik subklinis maupun klinis ditemukan lebih tinggi pada penderita AR. Mediator inflamasi aterogenik pada AR seperti interleukin-6 IL-6 diduga menjadi salah satu faktor risiko nontradisional kardiovaskular yang berkontribusi meningkatkan penanda disfungsi endotel seperti E-Selectin. Penelitian ini bertujuan mengetahui peran mediator inflamasi dalam kejadian disfungsi endotel, khususnya korelasi IL-6 dan E-selectin, pada pasien artritis reumatoid tanpa faktor risiko kardiovaskular. Studi potong-lintang dilakukan pada 40 pasien AR di Poliklinik Reumatologi RSUPN Dr. Cipto Mangunkusumo, Indonesia, pada bulan September-November 2017. Pemeriksaan IL-6 dan E-Selectin dilakukan dengan teknik enzyme-linked immunosorbent assay ELISA. Analisis korelasi bivariat dilakukan untuk menemukan korelasi kedua penanda tersebut. Rerata usia subjek penelitian ini adalah 44,9 13,1 tahun dan median durasi sakit adalah 36 bulan. Korelasi kadar IL-6 dengan kadar E-Selectin memiliki kekuatan korelasi lemah tetapi tidak bermakna secara statistik r = 0.232, p=0,149. Tidak terdapat korelasi antara IL-6 dengan E-Selectin pada pasien AR tanpa faktor risiko tradisional kardiovaskular.

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Rheumatoid arthritis RA is an autoimmune disease which has recently been recognized to manifest as not only intraarticular but also extraarticular symptoms. Cardiovascular events, presented either subclinically or clinically, were discovered more in AR patients. Atherogenic inflammatory mediator in AR including interleukin-6 IL-6 was thought to be one of nontraditional cardiovascular risk factor contributing to increase the endothelial dysfunction biomarker such as E-Selectin. This study was purposed to determine the correlation between inflammatory mediator and endothelial dysfunction event, especially between IL-6 and E-Selectin, in RA patient without traditional cardiovascular risk factor. A cross-sectional study was performed to 40 RA patients of Rheumatology Clinic of Cipto Mangunkusumo National General Hospital, Indonesia from September to November 2017. Measurement of the level of IL-6 and E-Selectin were performed using enzyme-linked immunosorbent assay ELISA. Bivariate correlation analysis was performed to determine the correlation between those two biomarkers. The mean age of this study subjects was 44.9 13.1 years and median of disease duration was 36 months. This study showed weak correlation between IL-6 and E-Selectin level, but not statistically significant.232, p=0.149 . There is no correlation between IL-6 and sE-Selectin in rheumatoid arthritis patient without traditional risk factor cardiovascular."

"ABSTRACTRheumatoid arthritis (RA) is an autoimmune disease which has recently been recognized to manifest as not only intraarticular events, presented either subclinically or clinically, were discovered more in AR patients. Atherogenic inflammatory mediator in AR including interleukin-6 (IL 6) was thought tobe one of nontraditional cardiovascular risk factor contributing to increase the endothelial dysfunction biomarker such as e selectin."

"Kejadian kardiovaskular adalah penyebab kematian utama pada artritis reumatoid AR . Periodontitis diketahui berperan dalam patogenesis disfungsi endotel pada AR. E-selectin merupakan penanda disfungsi endotel yang spesifik dihasilkan oleh endotel. Tujuan penelitian ini adalah mengetahui efek terapi periodontal terhadap kadar E-selectin pada pasien AR. Penelitian ini merupakan uji klinis randomisasi pada penderita AR yang berobat di Poliklinik Reumatologi RSCM periode Maret-Mei 2017. Pengambilan sampel dilakukan secara konsekutif. Randomisasi dilakukan dengan randomisasi blok. Subyek dibagi menjadi kelompok terapi periodontal dan kontrol. Dilakukan Uji t untuk melihat perbedaan selisih E-selectin awal dan akhir studi antara kelompok intervensi dengan kontrol. Periodontitis ditemukan pada 31 subyek 64,5 . Tidak didapatkan perbedaan selisih E-selectin awal dan akhir studi yang signifikan secara statistik antara kelompok intervensi dengan kontrol p=0,303 . Sebagai kesimpulan tidak didapatkan pengaruh terapi periodontal terhadap kadar E-selectin pada pasien AR.

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Cardiovascular event is the main cause of mortality in rheumatoid arthritis RA . Periodontitis is known to be involved in the pathogenesis of endothelial dysfunction in RA. E selectin is a marker of endothelial dysfunction and was expressed specifically in endothelial cells. The objective of this study was to determine the effect of periodontal treatment on E selectin level in RA patients. This was a randomized clinical trial in RA patients visiting Rheumatology Clinic RSCM between March May 2017. Samples were collected using consecutive sampling method. Randomization was done using block randomization. Subjects was divided into nonsugical periodontal treatment group and control group. T test was used to measure the difference of delta E selectin before after study between periodontal treatment group and control. Periodontitis was found in 31 subjects 64,5 . There was no statistically significant difference of delta E selectin before after treatment between periodontal treatment group and control. As a conclusion, periodontal treatment has no effect on E selectin level in RA patients."

"Latar Belakang: Komplikasi kardiovaskular yang disebabkan oleh disfungsi endotel menjadi salah satu penyebab mortalitas yang cukup tinggi pada pasien Artritis Reumatoid AR. Faktor Reumatoid RF merupakan autoantibodi yang sering dijumpai pada AR dan diduga dapat meningkatkan respon inflamasi dan disfungsi endotel. Sindroma metabolik dapat pula meningkatkan disfungsi endotel. Belum ada studi yang menilai korelasi RF dengan disfungsi endotel pada pasien AR tanpa sindroma metabolik.Tujuan: Mengetahui korelasi antara kadar RF dengan kadar VCAM-1 pada pasien AR tanpa sindroma metabolik.Metode: Penelitian desain potong lintang terhadap pasien AR dewasa yang berobat di Poliklinik Reumatologi RSUPN Cipto Mangunkusumo tanpa sindroma metabolik. Pengumpulan data dilakukan sejak Februari hingga Maret 2018 dari data penelitian sebelumnya yang diambil periode Februari 2016 hingga September 2017. Kadar RF dan VCAM-1 dinilai melalui pemeriksaan serum darah dengan metode ELISA. Analisis korelasi antar kedua variabel dibuat dengan SPSS 20,0.Hasil: Sebanyak 46 subjek diikutsertakan dalam penelitian ini. Sebagian besar 95,7 subjek adalah perempuan dengan rerata usia 44,43 tahun, median lama sakit 36 bulan, dan sebagian besar memiliki derajat aktivitas sedang 52,2. sebagian besar pasien memiliki RF positif 63. Korelasi antara kadar RF dengan kadar VCAM-1 memiliki kekuatan korelasi yang lemah tetapi tidak bermakna secara statistik r = 0,264; p = 0,076 . Subjek dengan RF positif memiliki kadar VCAM-1 yang lebih tinggi 626,89 vs 540,96 ng/mL. Simpulan: Belum terdapat korelasi antara RF dengan VCAM-1 pada pasien Artritis Reumatoid tanpa sindroma metabolik.

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Background: Cardiovascular complications caused by endothelial dysfunction become one of the highest causes of mortality in patients with Rheumatoid Arthritis RA . Rheumatoid Factor RF is an autoantibody that is commonly found in RA and is thought to increase the inflammatory response and endothelial dysfunction. Metabolic syndrome may also increase endothelial dysfunction. There have been no studies assessing correlation between RF and endothelial dysfunction in RA patients without metabolic syndrome.Aim: To determine the correlation between RF levels with VCAM-1 levels in RA patients without metabolic syndrome.Method: Cross sectional design study of adult AR patients treated in Rheumatology Polyclinic of Cipto Mangunkusumo General Hospital without metabolic syndrome. Data collection was conducted from February to March 2018 from the previous research data taken from February 2016 to September 2017. The levels of RF and VCAM-1 were assessed through blood serum testing using the ELISA method. Correlation analysis between the two variables was made with SPSS 20.0 for windows version.Results: A total of 46 subjects were included in the study. Most 95.7 subjects were women with an average age of 44.43 years, median duration of 36 months, and most had moderate activity 52.2. Most patients had a positive RF 63. The correlation between RF levels and VCAM-1 levels had a weak correlation strength but was not statistically significant r = 0.264; p = 0.076. Subjects with RF positive had higher VCAM-1 levels 626.89 vs 540.96 ng/mL.Conclusion: We did not found correlation between RF and VCAM-1 in Rheumatoid Arthritis patients without metabolic syndrome."

"ABSTRAKBackgrounds : There was a two-fold increase in cardiovascular-related mortality in rheumatoid arthritis (RA). Postprandial triglyceride (PPTG) related to increased risk of ischemic heart disease, myocardial infarction, ischemic stroke, mortality and elevated level of adhesion molecules. Increased endothelial adhesion molecules was a sign of endothelial activation, an early process in the development of atherosclerotic lesion. There was no study evaluating the role of NTG in cardiovascular risk assessment in RA patients. Aim : This study observed the relationship between PPTG and sICAM-1 and sE-selectin, as markers of endothelial activation. Methods : This was a cross-sectional study of fifty consecutively-recruited RA patients. Lipid profiles, sICAM-1, and sE-selectin were measured postprandially. Further analysis using multiple regression was performed. Results : There was no correlation found between PPTG and sICAM-1, nor NTG and sE-selectin. Level of sICAM-1 was influenced by HDL (R2=0,087) while sE-selectin was influenced by DAS-28 (R2=0,174), body mass index (R2=0,125), and postprandial glucose (R2=0,138). Conclusion : PPTG did not correlated with sICAM-1 and sE-selectin in RA patients.

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ABSTRACTBackgrounds : There was a two-fold increase in cardiovascular-related mortality in rheumatoid arthritis (RA). Postprandial triglyceride (PPTG) related to increased risk of ischemic heart disease, myocardial infarction, ischemic stroke, mortality and elevated level of adhesion molecules. Increased endothelial adhesion molecules was a sign of endothelial activation, an early process in the development of atherosclerotic lesion. There was no study evaluating the role of NTG in cardiovascular risk assessment in RA patients. Aim : This study observed the relationship between PPTG and sICAM-1 and sE-selectin, as markers of endothelial activation. Methods : This was a cross-sectional study of fifty consecutively-recruited RA patients. Lipid profiles, sICAM-1, and sE-selectin were measured postprandially. Further analysis using multiple regression was performed. Results : There was no correlation found between PPTG and sICAM-1, nor NTG and sE-selectin. Level of sICAM-1 was influenced by HDL (R2=0,087) while sE-selectin was influenced by DAS-28 (R2=0,174), body mass index (R2=0,125), and postprandial glucose (R2=0,138). Conclusion : PPTG did not correlated with sICAM-1 and sE-selectin in RA patients."

"ABSTRAKPenelitian ini bertujuan untuk mengetahui efek pemberian hidroksiklorokuin 400 mg selama 12 minggu terhadap kadar sVCAM-1 dan sE-Selectin sebagai petanda disfungsi endotel pada pasien artritis reumatoid. Penelitian ini juga melihat peran HOMA-IR, FFA dan ox-LDL terhadap perbaikan disfungsi endotel.Penelitian ini menggunakan dua disain yaitu uji klinis acak tersamar ganda dan kohort prospektif dilakukan pada pasien artritis reumatoid dengan terapi metotreksat di poliklinik Reumatologi RS Cipto Mangunkusumo, Jakarta, pada periode Februari 2016-Mei 2017. Pasien dengan terapi insulin, anti-hipertensi dan terapi lain yang mempengaruhi kadar sVCAM-1 dan sE-Selectin dieksklusi dari penelitian. Subjek yang eligibel dirandomisasi menjadi dua kelompok, kelompok yang mendapat hidroksiklorokuin HCQ 400 mg dan kelompok placebo, dan diikuti selama 12 minggu. Pemeriksaan sVCAM-1, sE-Selectin, HOMA-IR, FFA dan ox-LDL dilakukan pada awal penelitian dan pada minggu ke-12. Perbedaan persentase perubahan kadar sVCAM-1 dan sE-Selectin sebelum dan setelah perlakuan antara kedua kelompok dianalisis dengan uji-t dan uji Mann-Whitney. Persentase perubahan kadar sVCAM-1 dan sE-Selectin dikorelasikan dengan persentase perubahan HOMA-IR, FFA dan ox-LDL, dengan uji Spearman.Sebanyak 37 subjek diikutkan dalam penelitian, dan terdapat 3 subjek yang drop-out pada masing-masing kelompok, sehingga didapatkan 15 subjek pada kelompok HCQ dan 16 subjek pada kelompok placebo. Kadar sVCAM-1 serum minggu ke-12 pada kelompok HCQ menurun sebesar 17,1 median , sementara pada kelompok plasebo meningkat sebesar 9,7 , dan perbedaan tersebut bermakna secara statistik. Kadar E-Selectin pada kelompok terapi HCQ mengalami penurunan dalam persen yang lebih besar dibandingkan pada kelompok plasebo, tapi perbedaan tersebut tidak bermakna. Perubahan kadar sVCAM-1 dan sE-Selectin, juga dibuktikan tidak berkorelasi dengan perubahan HOMA-IR, FFA dan ox-LDL.Terapi hidroksiklorokuin pada pasien artritis reumatoid terbukti memperbaiki disfungsi endotel dengan menurunkan kadar sVCAM-1, namun tidak terbukti menurunkan sE-Selectin. Variable sVCAM-1 dan sE-Selectin tidak berkorelasi dengan HOMA-IR, FFA dan ox-LDL Kata kunci: artritis reumatoid, disfungsi endotel, hidroksiklorokuin, sE-Selectin, sVCAM-1.

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ABSTRACTThis study aims to evaluate the effect of hydroxychloroquine on sVCAM 1 and sE Selectin levels decreasing as endothelial dysfunction marker in rheumatoid arthritis patients. This study also assessed the correlation between changes in sVCAM 1 and sE Selectin levels with other variables of changes in HOMA IR, FFA and ox LDL.Two kinds of methods i.e. double blind randomized controlled trial and prospective cohort, were conducted, on patients with rheumatoid arthritis with methotrexate treatment at Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital Faculty of Medicine Universitas Indonesia, Jakarta, during February 2016 July 2017. Patients with insulin, anti hypertension and other treatment which could affect sVCAM 1 and sE Selectin level, were excluded. Eligible subjects were randomly assigned into two groups. Eighteen subjects were administered hydroxychloroquine 400 mg daily and 19 patients were given placebo for 12 weeks. sVCAM 1, sE Selectin, HOMA IR, FFA dan ox LDL were examined in the beginning and in the end week 12. Differences of serum sVCAM 1 and sE Selectin level in percentage, before and after experiment, were evaluated, by T test or alternatively by Mann Whitney test. Differences of serum sVCAM 1 and sE Selectin level in percentage, were correlated with difference of serum HOMA IR, FFA and ox LDL level, by Spearman test.There were 37 subjects enrolled in the study, and there were 3 drop out subjects in each group, finally there were 15 subjects in the HCQ group and 16 in the placebo group. Serum sVCAM 1 level decreased 17.1 median in HCQ treatment group, while in placebo group, it increased 9,7 median compared with pre treatment value. The difference in percentage rate change of sVCAM between two group was significant. On the other hand, the change of E Selectin serum level in HCQ group was found a higher percentage of decrease compared with placebo group, but the difference was not significant. Changes in sVCAM 1 and sE Selectin levels were also proven no correlation with HOMA IR, FFA and ox LDL changes.Treatment of HCQ in patients with rheumatoid arthritis appears beneficial to improve endothelial dysfunction by lowering serum sVCAM 1, but not proven to decrease sE Selectin. The sVCAM 1 and sE Selectin variables were not correlated with HOMA IR, FFA and ox LDL Keywords endothelial dysfunction, hydroxychloroquine, rheumatoid arthritis, sE Selectin, sVCAM 1."

"DETECTION OF VASCULAR ENDOTHELIAL DYSFUNCTION AS ANEARLY ATHEROSCLEROSIS MARKER:Effect of breastfeeding duration on vascular characteristicsand other cardiovascular risk factorsBackground. Atherosclerosis already starts to develop in childhood andadolescence. Breastmilk has been recognized to have some protective effects onthe development of atherosclerosis, but the optimal duration in relation tocardiovascular risk is largely unknown.Objective. To investigate the effect of breastfeeding duration on vascularcharacteristics and other cardiovascular risk factor levels in adolescence.Methods. We conducted a retrospective cohort study on adolescents aged 15-18years old. Breastfeeding duration was inquired using a questionnaire filled byparents and categorised into 0-<2, 2-<4, 4-<6, 6-<12, and >12 months. Outcomesassessed were flow mediated dilation (FMD), carotid intima media thickness(CIMT), anthropometrics, lipid/glucose level, high-sensitive C-reactive protein(hs-CRP), and vascular cell adhesion molecule (VCAM). Analysis was done usingANOVA and MANOVA general linear model with cardiovascular risk factors asthe dependent variables and breastfeeding duration as the independent variablewith further adjustment for confounders.Results. We enrolled 285 subjects. Breastfeeding duration of 4-<6 months wasassociated with thinner cIMT and the effect was more prominent after adjustmentfor gender and postnatal tobacco exposure (mean difference =24.28 micrometer, P=0.045). Both in univariable and multivariable analyses, breastfeeding duration of4-<6 months showed a statistically significant association with waist-to-hip ratio(0.87 vs. 0.81, P<0,001), but not with FMD, lipid profile, and other cardiovascularbiomarkers.Conclusions. Breastfeeding duration of 4-<6 months is associated with thinnerIMT and thus has a protective effect on the development of cardiovasculardisease. However the association with FMD and other cardiovascular risk factorlevels in adolescents is less clear

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DETEKSI DISFUNGSI ENDOTEL VASKULAR PADA REMAJA

SEBAGAI PENANDA AWAL ATEROSKLEROSIS:

Pengaruh lama pemberian air susu ibu pada masa bayi terhadap fungsi dan

struktur vaskular serta beberapa faktor risiko kardiovaskular lainnya

Latar belakang. Proses terjadinya aterosklerosis telah dimulai sejak masa anak.

Air susu ibu (ASI) diduga memiliki efek protektif terhadap perkembangan

aterosklerosis, tetapi lama pemberian ASI yang optimal terkait risiko

kardiovaskular belum diketahui secara pasti.

Tujuan. Mengetahui pengaruh lama pemberian ASI terhadap karakteristik

pembuluh darah dan faktor risiko kardiovaskular pada masa remaja.

Metodologi. Studi kohort retrospektif terhadap remaja usia 15-18 tahun. Data

mengenai lama pemberian ASI diperoleh dari kuesioner yang diisi oleh orangtua

dan dikelompokkan menjadi 0-<2, 2-<4, 4-<6, 6-<12, dan >12 bulan. Luaran

penelitian adalah flow-mediated dilation (FMD), ketebalan tunika intima media

(KTIM), profil lipid/glukosa darah, high-sensitive C-reactive protein (hs-CRP),

vascular cell adhesion molecule (VCAM) dan ukuran antropometri. Analisis

statistik dilakukan dengan uji ANOVA dilanjutkan dengan MANOVA general

linear model dengan faktor risiko kardiovaskular sebagai variabel dependen dan

lama pemberian ASI sebagai variabel independen dengan memperhitungkan

variabel perancu.

Hasil. 285 subjek diikutsertakan dalam penelitian. Lama menyusui 4-<6 bulan

berhubungan dengan KTIM arteri karotis yang lebih tipis baik analisis bivariat

maupun multivariat (beda rerata 24,28 mikrometer, p=0,045). Rasio lingkar

pinggang terhadap panggul sedikit lebih besar pada remaja dengan lama

pemberian ASI 4<6 bulan dibandingkan kelompok lain (0,87 vs. 0,81, p<0,001).

Lama pemberian ASI tidak menunjukkan hubungan yang bermakna dengan FMD

dan faktor risiko kardiovaskular lainnya.

Kesimpulan. Lama pemberian ASI 4-<6 bulan berhubungan dengan KTIM yang

lebih tipis sehingga mempunyai efek protektif terhadap terjadinya penyakit

kardiovaskular. Namun tidak ditemukan hubungan yang nyata antara lama

pemberian ASI dengan FMD dan faktor risiko kardiovaskular lainnya."

"Latar Belakang: Kehilangan massa tulang pada artritis reumatoid (AR) terjadi akibat ketidakseimbangan proses resorpsi dan formasi tulang. Tumor necrosis factor-α (TNF-a) adalah salah satu sitokin proinflamasi utama yang secara langsung dapat menyebabkan peningkatan resorpsi tulang, namun peranannya pada proses formasi tulang belum secara jelas diketahui. Aktivitas formasi tulang dapat dihambat oleh Dickkopf-1 (DKK-1) yang meningkat pada pasien AR. Penilaian turnover tulang dapat dilakukan dengan mengukur kadar C-terminal telopeptide (CTX) dan N-terminal propeptide (PINP) yang saat ini menjadi standar untuk penanda turnover tulang.Tujuan: Penelitian ini bertujuan untuk mendapatkan gambaran aktivitas turnover tulang pada pasien AR dengan melihat korelasi antara TNF-α dengan DKK-1 dan CTX untuk penilaian resorpsi tulang, dan korelasi antaran TNF-α dengan DKK-1 dan P1NP untuk penilaian formasi tulang.Metode: Penelitian ini merupakan studi potong lintang dengan 38 subjek artritis reumatoid perempuan premenopause. Pengambilan sampel dilakukan secara konsekutif di poliklinik reumatologi Rumah Sakit Cipto Mangunkusumo. Pemeriksaan TNF-α, DKK-1, CTX, dan P1NP dilakukan dengan metode ELISA.Hasil: Pada penelitian ini didapatkan median durasi menderita penyakit adalah 5 tahun. 60,5% pasien berada dalam kondisi remisi atau aktivitas penyakit rendah, 36,8% dalam kondisi aktivitas penyakit sedang, dan 2,6% pasien dalam kondisi aktivitas penyakit tinggi. Didapatkan median kadar TNF-a adalah 10.6 pg/mL, rerata kadar DKK-1 adalah 4027 pg/mL, rerata kadar CTX adalah 2,74 ng/mL, serta median nilai P1NP adalah 34 pg/mL. Kadar DKK-1 dan CTX dijumpai lebih tinggi sedangkan kadar P1NP lebih rendah jika dibandingkan dengan kadar pasien AR pada penelitian-penelitian sebelumnya. Penelitian ini menemukan korelasi positif lemah antara TNF-α dengan P1NP, sedangkan variabel lain tidak menunjukkan korelasi yang signifikan.Simpulan: Pada penelitian ini ditemukan korelasi positif lemah antara TNF-α dengan P1NP. Dijumpai kadar TNF-a yang rendah, DKK-1 yang tinggi, dan CTX yang tinggi dengan kadar P1NP yang rendah yang menunjukkan respon perbaikan tulang pada pasien AR tidak dapat mengimbangi tingginya aktivitas resorpsi tulang.

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Background: Bone mass loss in rheumatoid arthritis (RA) is due to the imbalance of bone resorption and formation process.Tumor necrosis factor-α (TNF-a) is one of the main proinflammatory cytokines that can directly increase bone resorption, but its effect on bone formation is still uncertain. Bone formation could be inhibited by Dickkopf-1 (DKK-1) that is increased in RA patients. Bone turnover could be determined by assessing the level of C-terminal telopeptide (CTX) and N-terminal propeptide (PINP), both are standard measurement for bone turnover markers.Objective: This study aims to examine bone turnover in RA patients by analysing correlation between TNF-α with DKK-1 and CTX for assesment of bone resorption, and correlation between TNF-α with DKK-1 and P1NP for assesment of bone formation.Methods: This is a cross-sectional study with 38 subjects of RA premenopausal women. The subjects were collected with consecutive sampling technique in rheumatology outpatient clinic in Rumah Sakit Cipto Mangunkusumo, Jakarta. Measurement of serum TNF-α, DKK-1, CTX, and P1NP levels were done using ELISA technique.Results: The median duration of RA in this study is 5 years. 60,5% of the patients were in remission or low activity disease, 36,8% were in moderate activity disease, and 2,6% were in high activity disease. The median value of TNF-a was 10.6 pg/mL, mean value of DKK-1 was 4027 pg/mL, mean value of CTX was 2,74 ng/mL, and mean value of P1NP was 34 pg/mL. DKK-1 and CTX levels were increased while P1NP level was lower compared to the RA patients in previous studies. This study found weak positive correlation between TNF-α and P1NP, while the other variables showed no significant correlation.Conclusions: This study demonstrated weak positive correlation between TNF-α and P1NP. We found low level of TNF-α, high level of DKK-1, and high level of CTX with low level of P1NP that indicate that the bone repair response could not keep up to the high bone resorption activity in RA patients."

"Artritis reumatoid (AR) dapat menyebabkan penurunan massa tulang sistemik akibat adanya peningkatan osteoklastogenesis dan penghambatan osteoblastogenesis melalui peningkatan sklerostin yang menyebabkan penghambatan jalur Wingless(Wnt)-bcatenin canonicaldan bone morphogenetic proteins(BMP). Sampai saat ini masih belum ada penelitian tentang korelasi TNF-adan sklerostin terhadap penanda turnovertulang (CTX dan P1NP) pada pasien AR perempuan premenopause.Penelitian ini bertujuan untuk menjelaskan patogenesis hilangnya massa tulang pada pasien artritis rheumatoid perempuan premenopause dengan menilai hubungan antara kadar sitokin proinflamasi TNF-α, penghambat Wnt signalingsklerostin, dan penanda resorpsi tulang P1NP dan CTX.Studi potong lintang ini melibatkan 38 perempuan AR premenopause. Pengambilan sampel dilakukan secara konsekutif. Pemeriksaan dilakukan dengan ELISA.Penelitian ini didapatkan kadar CTX (rerata 2,74 ng/ml) yang lebih tinggi dan P1NP (median 34,04 pg/ml) yang lebih rendahdibandingkan dengan sampel sehat pada penelitian sebelumnya. Terdapat korelasi negatif (r = -0,388) antara kadar TNF-α dengan kadar sklerostin yang bermakna secara statistik (p = 0,016). Terdapat pula korelasi positif (r = 0,362) antara kadar TNF-α dengan kadar P1NP yang bermakna secara statistik (p = 0,026). didapatkan adanya peningkatan CTX dan penurunan P1NP, adanya korelasi negatif bermakna antara kadar TNF-α dan sklerostin serta adanya korelasi positif bermakna antara kadar TNF-α dan P1NP.

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Rheumatoid arthritis is associated with systemic bone mass loss due tostimulation of osteoclastogenesis and inhibition of osteoblastogenesis through inhibition of Wingless(Wnt) -bcatenin canonical and bone morphogenetic proteins(BMP) pathway by sclerostin. There are currently no studies that assess the correlation of TNF-α and sclerostin with bone resorption markers CTX and P1NPin premenopause rheumatoid arthritis patients. This study aims to explainthe pathogenesis of bone mass decrease by assessing the correlation between TNF-α, sclerostin, P1NP and CTX. This cross-sectional study involves 38 premenopausal women with AR. Sampling is done consecutively. Examination is done by ELISA.

This study found higher level of serum CTX (mean 2,74ng/mL) and lower level of P1NP (median 34,04 pg/mL) than normal population in previous studies. There was a negative correlation (r = -0,388) between TNF-α levels and sclerostin levels which was significant (p = 0,016). There wasalso a positive correlation (r = 0,362) between TNF-α levels and P1NP levels which was also significant (p = 0,026). This study found an increase in CTX and decrease in P1NP. There was a significant negative correlation between TNF-α and sclerostin levels and also a significant positive correlation between TNF-α and P1NP levels."

"Latar Belakang: Aktivitas penyakit Artritis Reumatoid (AR) merupakan ekspresi dari kaskade inflamasi. Inflamasi jaringan sinovium yang disertai pembentukan pannus memerlukan asupan nutrisi dan oksigen melalui angiogenesis. Peningkatan penanda angiogenik menunjukkan inflamasi sendi yang progresif dan peningkatan aktivitas penyakit. Salah satu faktor pertumbuhan yang memiliki peran pada angiogenesis adalah nerve growth factor (NGF). Beberapa penelitian terdahulu mendapatkan kadar NGF yang meningkat baik pada serum maupun pada cairan sinovium pasien AR. Nerve growth factor (NGF) dapat menginduksi faktor-faktor pro-angiogenik dan faktor pertumbuhan lain yang berperan pada AR. Saat ini belum ada penelitian yang menghubungkan kadar serum NGF terhadap aktivitas penyakit AR. Tujuan: Mengetahui korelasi antara kadar NGF dengan aktivitas penyakit (yang dinilai dengan DAS28 LED dan DAS28 CRP) pada pasien AR di Rumah Sakit Cipto Mangunkusumo. Metode: Penelitian potong lintang yang mengevaluasi kadar NGF menggunakan two site immunoenzymatic assay (ELISA) pada 50 pasien (47 orang perempuan dan 3 orang laki-laki) AR di poliklinik Reumatologi Rumah Sakit Cipto Mangunkusumo pada Oktober sampai Desember 2015. Aktivitas penyakit AR pada penelitian ini dinilai menggunakan skor DAS28 LED dan DAS28 CRP melalui kalkulator yang diakses dari internet pada http://www.das-score.nl/. Analisis statistik bivariat digunakan untuk mendapatkan korelasi antara NGF dengan aktivitas penyakit AR. Hasil: Rerata usia subjek penelitian ini adalah 43,44 tahun. Median kadar serum NGF adalah 4,33 pg/mL (2,35-20,83). Hasil analisis memperlihatkan korelasi antara kadar serum NGF dengan skor DAS28 LED (r = +0,427; p = 0,002) dan DAS28 CRP (r =+0.407; p = 0,003). Kesimpulan: Terdapat korelasi positif sedang antara kadar serum NGF dengan aktivitas penyakit AR.

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Background: Disease activity of Rheumatoid Arthritis (RA) is an expression of the inflammatory cascade. Disease activity of a given joint is correlated with the synovial vascularization. Synovial tissue inflammation accompanied by pannus formation requires intake of nutrients and oxygen through angiogenesis. Angiogenesis plays an integral part of the development of the pannus formation. Increased angiogenic markers shows a progressive increase of joint inflammation and disease activity. One of the contributing factors to angiogenesis is the nerve growth factor (NGF). Several previous studies show increased NGF concentrations in both the serum and synovial fluid of RA. Nerve growth factor can induce pro-angiogenic factors and other growth factors contribute in RA. Currently, there has not been any studies yet that correlates the NGF serum concentration with RA disease activity.

Objective: To determine the correlation between the serum concentration of NGF and disease activity of RA patients at Cipto Mangunkusumo General Hospital (using DAS28 ESR and DAS28 CRP score).

Methods: A cross-sectional study was used. Recruited were 50 RA patients (47 women and 3 men) of outpatient clinic of Rheumatology at Cipto Mangunkusumo General Hospital from October to December 2015. Concentrations of NGF were evaluated with a two site immunoenzymatic assay (ELISA). Disease activity in this study was assessed using DAS28 ESR and DAS28 CRP score using a calculator accessible from the internet on http://www.das-score.nl/. The correlation between NGF with disease activity was analyzed by bivariate analysis.

Results: The mean age of the study subjects was 43.44 years. Median serum NGF was 4.33 pg / mL (2.35 to 20.83). The results shows correlation between serum NGF with DAS28 ESR (r = +0.427; p = 0.002) and DAS28 CRP (r = + 0407; p = 0.003).

Conclusion: Significant positive correlation between serum concentration of NGF with diesease activity in patient with AR was found."