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"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."

"Lupus eritematosus sistemik merupakan penyakit autoimun sistemik yang menghasilkan berbagai autoantibodi yang ditujukan terhadap komponen sel, seperti inti sel, sitoplasma dan membran sel. Salah satu autoantibodi tersebut yaitu antibodi anti ?2GP-1 dihubungkan dengan kejadian aterosklerosis dan penyakit kardiovaskular yang timbul lebih dini pada pasien SLE. Penelitian ini bertujuan untuk mengetahui hubungan antibodi anti ?2GP-1 dengan disfungsi endotel dan aterosklerosis pada pasien SLE dan disfungsi endotel pada HUVEC. Penelitian potong lintang pada pasien SLE yang memenuhi kriteria inklusi menurut ACR 1997 di poliklinik khusus Reumatologi, Alergi Imunologi RSCM dan poliklinik khusus Reumatologi RSUP Dr. M. Djamil dari Maret 2016 sampai dengan Juli 2017. Subjek secara acak dibagi atas 2 kelompok berdasarkan nilai CIMT. Dilakukan pemeriksaan antibodi anti ?2GP-1, ox-LDL, ADMA, ICAM-1, VCAM-1, ET-1. Dilakukan pemajanan antibodi anti ?2GP-1 yang berasal dari kelompok aterosklerosis positif dan kontrol pada HUVEC. Enam puluh enam orang subjek direkrut pada penelitian ini, terdiri atas 33 orang aterosklerosis positif dan 33 orang aterosklerosis negatif dan 6 orang kontrol dengan rentang umur 20-45 tahun. Ditemukan korelasi positif antara antibodi anti ?2GP-1 dengan CIMT,ADMA, ICAM-1, VCAM-1 dan ET-1 dengan nilai r = 0,409, 0,89, 0,36, 0,43, 0,37 dan dengan p < 0,05. Tidak ditemukan korelasi antibodi anti ?2GP-1 dengan ox-LDL dengan r = 0,025 dan p > 0,05. Ditemukan perbedaan bermakna kadar antibodi anti ?2GP-1, ADMA, ICAM-1, VCAM-1 dan ET-1 pada kelompok aterosklerosis positif dengan kelompok aterosklerosis negatif dengan nilai p < 0,05, sedangkan kadar ox-LDL tidak ada perbedaan bermakna pada kedua kelompok tersebut dengan nilai p > 0,05. Hasil pemajanan antibodi anti ?2GP-1 pada HUVEC mendapatkan perbedaan bermakna peningkatan kadar ICAM-1, VCAM-1 dan ET-1 pada kelompok SLE aterosklerosis positif dari kontrol dengan nilai p < 0,05. Antibodi anti ?2GP-1 menimbulkan disfungsi endotel pada pasien SLE.

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Systemic lupus erythematosus SLE is a multi systemic disease characterized by a wide variety of autoantibodies directed to several self molecules found in the nucleus, cytoplasm and cell membrane. One of variety autoantibodies is Antibody anti 2GP 1 which associated with atherosclerosis and premature cardiovascular disease in SLE patients. The purpose of the study is to know the association of antibody anti 2GP 1 with endothelial dysfunction and atherosclerosis in SLE and endothelial dysfunction in HUVEC. Cross sectional study was performed in SLE patients fulfill inclussion criteria according ACR 1997 out patients in Rheumatology and Alergy Immunology polyclinic of Cipto Mangunkusomo Hospital and Dr. M. Djamil Hospital from March 2016 to July 2017. Patients were divided in 2 groups based on CIMT. Examination of antibody anti 2GP 1, ox LDL, ADMA, ICAM 1, VCAM 1 and ET 1 were performed. Purified antibody anti 2GP 1 from positive atherosclerosis and controls groups were exposed to HUVEC. Sixty six patients were enrolled, consists of 33 patients with positive atherosclerosis, 33 patients with negative atherosclerosis and 6 as healthy control with range of age 20 40 year. In this study we found positive correlation between antibody anti 2GP 1 with CIMT, ADMA, ICAM 1, VCAM 1 and ET 1 with r 0.409, 0.89, 0.36, 0.43, 0.43 respectively and p value 0.05. There was no correlation between antibody anti 2GP 1 with ox LDL, r 0.025 and p 0.05. There were significantly different levels of antibody anti 2GP 1, ADMA, ICAM 1, VCAM 1 and ET 1 in positive atherosclerosis compared to negative atherosclerosis group with p 0.05. Level of ox LDL was not different between the two groups with p 0.05. There were significantly different increase of ICAM 1, VCAM 1 and ET 1 levels in HUVEC which was exposed with purified antibody anti 2GP 1 from positive atherosclerosis compared to control with p 0.05. Antibody anti 2GP 1 cause endothelial dysfunction in SLE patients. "

"Kondisi hipertiroidisme berkorelasi dengan kejadian atherosclerosis cardiovascular disease (ASCVD). Hal ini dapat terjadi melalui jalur resistensi insulin, metabolisme lipid, dan inflamasi yang dapat menyebabkan disfungsi endotel. Sebaliknya, pemberian obat antitiroid seperti propiltiourasil (PTU) atau metimazol memiliki potensi untuk memperbaiki disfungsi endotel yang terjadi. PTU memiliki keunggulan dibandingkan metimazol dalam hal menghambat migrasi dan proliferasi otot polos vaskular. Studi ini bertujuan untuk mempelajari peran hormon tiroid dan pengobatannya pada pasien Graves terhadap penanda dini aterosklerosis.Studi ini merupakan uji klinis tersamar tunggal yang dilakukan di RSUPN Dr. Cipto Mangunkusumo (RSCM) pada pasien Graves baru yang diberikan PTU atau metimazol selama 3 bulan. Kedua kelompok diperiksakan HOMA-IR,LDL-R, NF-kB, sICAM-1, sVCAM-1 dan sE-selektin serta pulse wave velocity (PWV) dan carotid intima media thickness (cIMT) saat sebelum terapi, setelah terapi 1 bulan dan 3 bulan. Dilakukan uji Pearson atau Spearman untuk menilai korelasi antar variabel. Perubahan variabel dalam 3 bulan dinilai dengan uji repeated ANOVA. Perbedaan pada kelompok PTU dan metimazol dinilai dengan uji general linear model.Selama bulan Juli 2019 hingga Agustus 2020, didapatkan 36 pasien Graves baru. Pada uji korelasi didapatkan konsentrasi T4 bebas berkorelasi dengan sICAM-1(r = 0,41; p = 0,013) dan sVCAM-1 (r = 0,458; p = 0,005), begitu juga T3 total berkorelasi dengan sICAM-1 (r = 0,513; p = 0,001) dan sVCAM-1 (r = 0,567;p < 0,001). Pada tindak lanjut 3 bulan, didapatkan 24 subjek (13 kelompok PTU dan 11 kelompok metimazol) yang menyelesaikan pemeriksaan dan mencapai eutiroid. Pada kelompok PTU, didapatkan penurunan LDL-R (p = 0,017),sICAM-1 (p = 0,001), sVCAM-1 (p < 0,001) dan sE-selektin (p = 0,045). Pada kelompok metimazol terjadi penurunan hanya pada LDL-R (p = 0,011) dan sVCAM-1 (p = 0,001). Namun pada perbandingan kedua kelompok tidak berbeda bermakna. Parameter PWV dan cIMT juga tidak berbeda bermakna.Simpulan: Pada penelitian ini kondisi hipertiroid pasien Graves berkorelasi dengan peningkatan sICAM-1 dan sVCAM-1 sebagai penyebab aterosklerosis. Pemberian obat antitiroid dapat menurunkan LDL-R, sICAM-1, sVCAM-1 dan sE-selektin. PTU memiliki mekanisme yang berbeda dari metimazol dalam patofisiologi aterosklerosis. Akan tetapi, belum didapatkan bukti pada perubahan PWV dan cIMT

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Hyperthyroidism is correlated with atherosclerosis cardiovascular disease (ASCVD). The basic mechanisms are through insulin resistance, lipid metabolism, and inflammation resulted in endothelial dysfunction. On the other hand, antithyroid drugs such as propiltiourasil (PTU) or methimazole have the potential to improve the endothelial dysfunction. PTU is believed to have a better profile than methimazole in reducing smooth muscle cells migration and proliferation. This study aims to investigate the effect of thyroid hormone and its treatment in Graves’ disease to early marker of atherosclerosis.

This study is a single-blinded clinical trial conducted in dr. Cipto Mangunkusumo General Hospital (RSCM) to newly diagnosed Graves’ patient treated with PTU or methimazole for 3 months. Both groups were examined for LDL-R, NF-ĸB, sICAM-1, sVCAM-1, sE-selectin, pulse wave velocity (PWV) and carotid intima media thickness (cIMT) at baseline, after 1 month and 3 months treatment. Pearson or Spearman test was done to analyze correlation between tested variables. Repeated ANOVA test was done to analyze the changes in those variables during 3 months treatment. Difference between PTU and methimazole groups was analyzed with general linear model test.

From July 2019 to August 2020, 36 newly diagnosed Graves’ patients were included in the study. Correlation test showed free T4 concentration correlated to sICAM-1 (r = 0.41; p = 0.013) and sVCAM-1 (r = 0.458; p = 0.005), and total T3 also correlated to sICAM-1 (r = 0.513; p = 0.001) and sVCAM-1 (r = 0.567; p < 0.001). After 3 months follow up, 24 subjects (13 from PTU group and 11 from methimazole group) reached euthyroid state and included in the analysis. In PTU group, we found reduction in LDL-R (p = 0.017), sICAM-1 (p = 0.001),

sVCAM-1 (p < 0.001) and sE-selectin (p = 0.045). While in methimazole groups, we only found reduction in LDL-R (p = 0.011) and sVCAM-1 (p = 0.001). However, after comparing both groups, the differences were not statistically significant. We found no significant changes in PWV and cIMT parameter.

In conclusions, this study found that hyperthyroidism in Graves’ patient correlated with increase in sICAM-1 and sVCAM-1, which are the early markers of atherosclerosis. Antithyroid drugs can lower LDL-R, sICAM-1, sVCAM-1 and sE-selectin. PTU had a different mechanism in pathophysiology of atherosclerosis compared to methimazole. However, we found no evidence in PWV and cIMT changes"