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PROTEINURIA SEVERITY IN LUPUS NEPHRITIS IS ASSOCIATED WITH ANTI-DSDNA LEVEL AND IMMUNE COMPLEX DEPOSIT LOCATION IN KIDNEY Engli, Katherina; Handono, Kusworini; Eko, Mudjiwijono Handaru; Susianti, Hani; Gunawan, Atma; Kalim, Handono
Journal of Tropical Life Science Vol 8, No 3 (2018)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.08.03.03

Abstract

Lupus nephritis (LN) is one of the manifestations of Systemic Lupus Erythematosus (SLE), with proteinuria being one of the clinical manifestations. The proteinuria pathogenesis is associated with anti-dsDNA antibody and the location of immune complex deposits within the kidney. This study aims to investigate the correlation of the severity of proteinuria with the location of immune complex deposits and the level of anti-dsDNA antibody in LN. Data were collected in cross-section. Fifty-three patients with LN in Saiful Anwar Hospital Malang, who underwent renal biopsy, were included. Hematoxylin-eosin staining and immunofluorescence analysis were used to assign subjects to different histopathological classes and determine the immune complex deposits. The spot urine samples were evaluated using the dipstick method for semi-quantitative proteinuria. The anti-dsDNA antibody levels were evaluated using the enzyme-linked immunosorbent assay (ELISA). Turbidity and enzymatic tests were conducted to elucidate urine protein and creatinine content, respectively. The level of proteinuria is significantly different among the different locations of immune complex based on the dipstick and protein/creatinine methods (p = 0.021 and p = 0.005, respectively). There was a significant correlation between anti-dsDNA antibody level and the severity of proteinuria (r = 0.326 based on dipstick and r = 0.28 based on protein/creatinine method). Thus, proteinuria in LN is determined by anti-dsDNA level and the location of immune complex deposits in the kidney.
KADAR ANTIBODI ANTI-DSDNA DAN URINE MONOCYTE CHEMOATTRACTANT PROTEIN-1 PADA NEFRITIS LUPUS Susianti, Hani; Salman, Yuliana; Gunawan, Atma; Handono, Kusworini
Jurnal Kedokteran Brawijaya Vol 27, No 2 (2012)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jkb.2012.027.02.8

Abstract

ABSTRAKKata Kunci: Lupus  eritematosus  sistemik  (LES) merupakan  penyakit  autoimun  yang  ditandai  oleh  peradangan  kronis  dan  akut. Biomarker klasik untuk mendeteksi adanya penyakit LES adalah antibody anti-double stranded DNA (anti-dsDNA) dan urine Monocyte Chemoattractant Protein-1   (uMCP-1).   Penelitian ini dilakukan untuk mengkaji hubungan antara kedua biomarker tersebut dengan klasifikasi histopatologis nefritis lupus untuk mengganti biopsi ginjal dalam penentuan kelas histopatologi nefritis lupus.   Penelitian ini dilakukan selama 11 bulan   berupa studi observasional dengan pengambilan sampel darah dan urin untuk mengetahui kadar antibodi anti-dsDNA dan MCP-1, serta biopsi ginjal untuk menentukan kelas nefritis lupus berdasarkan klasifikasi WHO tahun 1982.   Data hasil penelitian menunjukkan tidak ada perbedaan yang signifikan (p=0,208>?) antara mean rank kadar anti-dsDNA pada kelompok kontrol dan kelompok kasus,begitu pula dengan hasil perbandingan mean rank kadar uMCP-1 (p=0,247>?).   Uji korelasi Spearman's rho,menunjukkan hubungan signifikan kadar anti-dsDNA dan kadar uMCP-1 (r = 0,861; p<0,001). Dapat disimpulkan bahwa tidak terdapat perbedaan kadar biomarker antibodi anti-dsDNA dan urine MCP1 pada kejadian nefritis lupus dan klasifikasi histopatologi nefritis lupus, namun terdapat hubungan yang sangat erat antara kadar biomarker antibodi anti-dsDNA dengan kadar urine MCP-1. Nilai sensitifitas kadar anti-dsDNA dan uMCP-1  lebih rendah yaitu 20% ? 40% dibandingkan dengan nilai spesifisitasnya, yaitu 50% ? 83,33%.Kata Kunci: Anti-dsDNA, uMCP-1, klasifikasi histopatologi, nefritis  lupus
Urine Specific Proteins and Alpha-1 Antitrypsin Concentrations to Assess the Severity of Lupus Nephritis Susianti, Hani; Barlianto, Wisnu; Hanggara, Dian Sukma; Handono, Kusworini; Adipireno, Purwanto; Suromo, Lisyani
Research Journal of Life Science Vol 4, No 1 (2017)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (875.828 KB) | DOI: 10.21776/ub.rjls.2017.004.01.6

Abstract

Background. Current biomarkers for evaluating disease activity or severity in lupus nephritis (LN) are considered to be unsatisfactory. Pathological changes in glomerular basement membrane and selectivity of electrical discharge are causing specific patterns of urine proteins excretion. Together with alpha-1 antitrypsin (AAT), they are expected to become new biomarkers to assess LN activity.Method. Seventy-one urine samples were collected from healthy controls and LN patients. Patterns of urine specific proteins were determined using column chromatography and SDS-PAGE tests, LN activity was calculated using SLEDAI-renal domain score, and AAT concentrations was measured by ELISA.Result. The majority of proteins in the control group have molecular weights of >66 kDa (88%) and 21- to 25-kDa proteins were observed only in the case group. The p values for differences in urine AAT concentration between active LN and healthy controls, inactive LN and healthy controls, and active LN and inactive LN were 0.004, 0.046, and 0.054, respectively, whereas those for urine AAT/creatinine ratio were 0.489, 0.019, and 0.915, respectively.Conclusion: There were differences in the patterns of the molecular weight of proteins and urine AAT concentrations between case group and control group. However, no such differences were identified between active and inactive LN. 
Development of Candidate Antigens for Rapid Test Kit to Detect Autoantibodies in Patients with Systemic Lupus Erythematosus Barlianto, Wisnu; Susianti, Hani; Wahono, Singgih; Ismayasih, Nelly; Meilani, Rossy; Handono, Kusworini
Research Journal of Life Science Vol 4, No 1 (2017)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (693.941 KB) | DOI: 10.21776/ub.rjls.2017.004.01.8

Abstract

Systemic Lupus Erythematosus (LES) is an autoimmune inflammatory disease characterized by the formation of anti-nuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) antibodies as diagnostic markers. Detection of such autoantibodies requires advanced equipment and trained personnel.This study was conducted to acquire candidate antigens that can be used for rapid test kit for practical and accurate detection of ANA and anti-dsDNA to speed up SLE diagnosis.Nuclear proteins and DNA derived from cell lines, hair follicles, and leukocytes of SLE patients and healthy individuals were isolated using QiaGEN kit and modified-manual procedure. Antigen-antibody bonds were tested by dot blot assay.The strongest binding between DNA antigens of a healthy individual and antibodies occurred at dilution factors of 1:5,120 for the antigen and 1:2,560 for the antibody. The strongest binding between nuclear protein antigens from the cell line and antibodies occurred at dilution factors of 1:512 for the antigen and 1:1,600 for the antibody.Nuclear antigens derived from cell line and DNA antigens of healthy individuals were antigen candidates for the development of ANA and anti-dsDNA rapid detection tests.
Differences Between Alpha-Fetoprotein (AFP) and Prothrombine Induced by Vitamin K Absence or Antagonist II (PIVKA-II) Values as Early Detection Method for Hepatocellular Carcinoma (HCC) and Cirrhosis Nugraha, Bayu Eka; Setiawan, Nugraha; Susianti, Hani; Pratomo, Bogi
The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy Vol 19, No 3 (2018): VOLUME 19, NUMBER 3, December 2018
Publisher : The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (412.214 KB) | DOI: 10.24871/1932018153-157

Abstract

Background: Hepatocellular carcinoma is a common cancer worldwide and has a high mortality. Biomarkers could theoretically help to detect the disease at an earlier stage before symptoms occur and improve the treatment outcomes. The first biomarker found was AFP (not very accurate and 30-40% of HCC may be missed). PIVKA-II can be used as an early detection method to diagnose HCC.Method: A cross sectional study on in-patients or out-patients at Saiful Anwar Malang Hospital from July 2016 to October 2016.Results: The p value (p > 0.05) obtained using Kolmogorov-Smirnov was 0.166 for diagnosis of HCC and 0.147 for the diagnosis of hepatic cirrhosis. The p value (p > 0.05) obtained using Shapiro-Wilk was 0.103 for diagnosis of HCC and 0.087 for the diagnosis of cirrhosis. Comparative test using the LSD method showed PIVKA-II serum levels in HCC as compared to hepatic cirrhosis as significant with a p-value less than 0.05 (p < 0.05), that is 0.025. However comparative test using the Tukey HSD method showed that the results obtained were not significant. According to the PIVKA-II cut off value, the sensitivity and specificity to detect cirrhosis and HCC was as large as 100%. According to the AFP cut off value, the sensitivity to detect cirrhosis and HCC was 93.3% and the specificity was 76.92%.Conclusion: Both PIVKA-II and AFP can be used to detect cirrhosis and HCC. However PIVKA-II exhibited better sensitivity and specificity in the detection of cirrhosis and HCC.
Differences Between Alpha-Fetoprotein (AFP) and Prothrombine Induced by Vitamin K Absence or Antagonist II (PIVKA-II) Values as Early Detection Method for Hepatocellular Carcinoma (HCC) and Cirrhosis Nugraha, Bayu Eka; Setiawan, Nugraha; Susianti, Hani; Pratomo, Bogi
The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy Vol 19, No 3 (2018): VOLUME 19, NUMBER 3, December 2018
Publisher : The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (412.214 KB) | DOI: 10.24871/1932018153-157

Abstract

Background: Hepatocellular carcinoma is a common cancer worldwide and has a high mortality. Biomarkers could theoretically help to detect the disease at an earlier stage before symptoms occur and improve the treatment outcomes. The first biomarker found was AFP (not very accurate and 30-40% of HCC may be missed). PIVKA-II can be used as an early detection method to diagnose HCC.Method: A cross sectional study on in-patients or out-patients at Saiful Anwar Malang Hospital from July 2016 to October 2016.Results: The p value (p > 0.05) obtained using Kolmogorov-Smirnov was 0.166 for diagnosis of HCC and 0.147 for the diagnosis of hepatic cirrhosis. The p value (p > 0.05) obtained using Shapiro-Wilk was 0.103 for diagnosis of HCC and 0.087 for the diagnosis of cirrhosis. Comparative test using the LSD method showed PIVKA-II serum levels in HCC as compared to hepatic cirrhosis as significant with a p-value less than 0.05 (p < 0.05), that is 0.025. However comparative test using the Tukey HSD method showed that the results obtained were not significant. According to the PIVKA-II cut off value, the sensitivity and specificity to detect cirrhosis and HCC was as large as 100%. According to the AFP cut off value, the sensitivity to detect cirrhosis and HCC was 93.3% and the specificity was 76.92%.Conclusion: Both PIVKA-II and AFP can be used to detect cirrhosis and HCC. However PIVKA-II exhibited better sensitivity and specificity in the detection of cirrhosis and HCC.
PETANDA BIOLOGIK TERKINI LUPUS NEFRITIS Susianti, Hani; Handono, Kusworini
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 20, No 2 (2014)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v20i2.1085

Abstract

Lupus Nephritis (LN) is one of the serious clinical manifestation of Systemic Lupus Erythematosus (SLE). Early detection and treatmentof renal activity may spare patients from renal damage. Conventional biomarkers such as urine sediment, proteinuria, creatinine, antidsDNA antibody and their complement levels are not specific and sensitive enough in detecting the ongoing disease activity in the lupuskidneys and early relapse of nephritis. Renal biopsy is the gold standard in providing information on the histopathology of LN, but isinvasive and it should take a serial of biopsies making it impractical when monitoring LN. Thus, some novel biomarkers are necessary toenhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response anddetection of early renal flares as well. Some novel biomarkers have been studied in LN, however, validation on a large scale of patientswith different ethnic backgrounds is still needed.
Diagnostic Test of PIVKA-II as A Tumor Marker for Hepatocellular Carcinoma (HCC) Djatmiko, Dwi Priyadi; Santosa, I Putu Adi; Lawanto, Elvin Richela; Pratomo, Bogi; Susianti, Hani
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 26, No 2 (2020)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v26i2.1436

Abstract

Introduction. Alpha-Fetoprotein (AFP) is a tumor marker that has been widely used for HCC, but there has been no increased AFP in 35-45% patients with HCC. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin secreted in HCC and is expected can be used for HCC diagnostic marker. The objective of this study was to compare serum PIVKA-II levels in the patients with HCC, cirrhosis and healthy control and determine the diagnostic value of PIVKA-II for hepatocellular carcinoma. Methods. This was a cross-section analytic observational study to identify the diagnostic value of PIVKA-II for HCC diagnosis. The diagnosis of 20 cirrhotic patients and 15 patients with HCC was established by history taking, physical examination, and additional examination according to the diagnosis criteria. A group of 12 individuals with normal liver function were used as healthy control subjects. Serum PIVKA-II levels were analyzed with immunoassay method. Comparison study used the Independent-Samples Kruskal Wallis Test. ROC curve analysis and 2x2 contingency table was used to calculate sensitivity, specificity, positive and negative predictive value (PPV and NPV).Results. The serum PIVKA-II level in the patients with HCC was significantly higher than in cirrhotic (p = 0,000) and healthy control patients (p = 0,000). Sensitivity, specificity, PPV, and NPV of PIVKA-II for diagnosis of HCC in cirrhotic patients at a cut-off value of 140.85 mAU/mL were 93.33%, 75%, 73.68%, and 93.75%, respectively (AUC = 0.87).Conclusions and Suggestions. PIVKA-II has high diagnostic value for HCC diagnosis. Diagnostic test that compare serum PIVKA-II level in any size of HCC nodules may be needed in the future.
EVALUATION OF URINE PROCALCITONIN, INTERLEUKIN-6, HEPARIN BINDING PROTEIN, LEUKOCYTURIA, AND BACTERIURIA FOR EARLY DETECTING URINARY TRACT INFECTION Susianti, Hani; Santosa, I Putu Adi; Johanes, Antonius; Mayrita, Esther; Merdikaningsih, Thiba Dina
Research Journal of Life Science Vol 6, No 1 (2019)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.rjls.2019.006.01.2

Abstract

Urinary Tract Infection (UTI) is a common infectious disease. Urine culture as a gold standard is less practical and time- consuming. Examination of urine dipstick and microscopic is less accurate. Procalcitonin (PCT), IL-6 and Heparin Binding Protein (HBP) have known increase after infection, which potentially used for early detection of UTI. The aim of this study was to determine the diagnostic performance of urine IL-6, HBP, PCT, leukocyturia and bacteriuria level as biomarkers of UTI. The study was conducted on 51 UTI patients with positive urine culture, 16 UTI patients with negative urine culture, and 16 healthy control.  Urine IL-6, HBP, and PCT level were determined using ELISA. Leukocyturia and bacteriuria were measured using automated flowcytometry and fluorescent dye analyzers.  The gold standard for UTI diagnosis was urine culture. The sensitivity and specificity of urine PCT, IL-6, HBP, leukocyturia and bacteriuria were 60.78% and 65.62%; 72.55% and 56.25%; 96.07% and 50.00%; 80.39% and 78.12%; 80.39% and 59.09% respectively. The AUC of urine PCT, IL-6, HBP, leukocyturia and bacteriuria were 0.600; 0.605; 0.666; 0.877 and 0.830 respectively. For combinations of two biomarkers, the best sensitivity and specificity was demonstrated by urine PCT and leukocyturia.
INTERLEUKIN-4 DAN INTERFERON GAMMA DI NEFRITIS LUPUS: HUBUNGAN AKTIVITAS PENYAKIT SERTA KEKAMBUHAN Achamar, Torajasa; Farida, Dany; Susianti, Hani; Handono, Kusworini; Rastini, Ati; R.I, R.I; A.S, I Putu; Gunawan, Atma; Kalim, Handono
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 22, No 2 (2016)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v22i2.1117

Abstract

Sampling for urinalysis to see the activity and the degree of recurrence of Lupus Nephritis (LN) is very difficult. New biomarkersthat are more simple, sensitive, specific and non-invasive in assessing the activity of the LN need to be investigated. Interleukin-4 (IL-4)and interferon gamma (IFN-?) were implicated to LN process. Urine samples from 17 LN patients were taken every month for 6 (six)months to examine the level of uIL-4, uIFN-?, activity and recurrence of LN. Significant differences were observed in the uIFN-? levelsbetween the active and inactive LN groups (p=0.012), but not in uIL-4 levels (p=0.187). Correlations between each biomarker andrenal domain score were weak (r=0.201, p=0.042 for uIL-4; r=0.268, p=0.006 for uIFN-?). Significant differences were also found inthe uIL-4 and uIFN-? levels against LN recurrence (p=0.033; p=0.017). The best cut off values to assess recurrences and activity of LNwere 8.17 pg/mL for uIL-4 showed a sensitivity of 74%, specificity 71%, NPV 90%, PPV 42% to assess recurrences and to assess activityof LN showed sensitivity 46%, specificity 75%, NPV 48%, PPV 78%. The cut off 18.58 pg/mL for uIFN-? to predict recurrent and assessthe activity of LN showed sensitivity 68%%, specificity 70%, NPV 88%, PPV 40% to predict the recurrent and to assess the activity of LNshowed sensitivity 57%, specificity 64%, NPV 49%, PPV 73%. Based on the research, uIL-4 and uIFN-? are not good enough to predictrecurrence and activity of LN