Disertasi

Panel Baru Diagnosis Tuberkulosis Intestinal: Tinjauan Khusus Kadar TLR-2 pada Kolonosit Tereksfoliasi. = New Panel for Diagnosis of Intestinal Tuberculosis: Special Review of TLR-2 Levels in Exfoliated Colonocytes.

Penyakit tuberkulosis (TB) di Indonesia masih sangat tinggi dan menduduki urutan kedua di dunia pada tahun 2021. Kesulitan diagnosis tuberkulosis intestinal (TBI) antara lain manifestasi klinis penyakit TBI yang menyerupai penyakit lain, keterbatasan pemeriksaan laboratorium, dan pemeriksaan kolonoskopi yang invasif, sehingga perlu dikembangkan suatu panel pemeriksaan laboratorium skrining noninvasif dengan berbagai biomarka laboratorium. Penelitian ini adalah studi potong lintang, bertujuan untuk mendapatkan panel diagnosis TBI melalui pemeriksaan Polymerase Chain Reaction (PCR) TB feses, hematologi (hitung leukosit, hitung jenis leukosit, Rasio Neutrofil terhadap Limfosit (RNL), Rasio Monosit terhadap Limfosit (RML), dan Laju Endap Darah (LED)), Interferon-γ (IFN-γ) feses, Human Beta Defensin-2 (HBD-2) feses, Interferon Gamma Releasing Assay (IGRA) darah, Adenosine Deaminase (ADA) darah, ekspresi Toll Like Reseptor-2 (TLR-2) feses dan kolonosit tereksfoliasi. Penelitian dilakukan di Departemen Ilmu Penyakit Dalam (IPD), Pusat Endoskopi Saluran Cerna (PESC), Laboratorium Patologi Anatomi, dan Laboratorium Patologi Klinik di RSUPN dr. Cipto Mangunkusumo (RSUPNCM) sejak November 2020−Desember 2022. Subjek penelitian adalah pasien dewasa terduga TBI yang menjalani kolonoskopi dan pemeriksaan laboratorium histopatologi, PCR TB feses, hematologi (hitung leukosit, hitung jenis leukosit, RNL, RML, dan LED), IFN-γ feses, HBD-2 feses, IGRA darah, ADA darah, dan ekspresi TLR-2 dari feses dan kolonosit tereksfoliasi. Dari 143 subjek terduga TBI, didapatkan 22 subjek TBI dan 121 subjek NonTBI. Tidak didapatkan perbedaan bermakna pada hitung leukosit, hitung jenis leukosit, RNL, RML, proporsi positif IGRA, kadar HBD-2 feses, ekspresi TLR-2 feses, dan ekspresi TLR-2 kolonosit tereksfoliasi pada subjek TBI dan NonTBI. Didapatkan proporsi PCR TB feses positif, LED, ADA darah, dan kadar IFN-γ yang lebih tinggi bermakna pada kelompok subjek TBI dibandingkan NonTBI. Tidak terdapat perbedaan bermakna ekspresi TLR-2 pada feses dan kolonosit tereksfoliasi. Didapatkan nilai cut-off, sensitivitas, dan spesifisitas terbaik pada pemeriksaan ADA, HBD-2 feses, IFN-γ feses, RNL, RML, dan LED. Didapatkan usulan panel Model II (5 biomarka) yang telah memenuhi validasi internal dan lebih murah dalam aplikasi klinisnya.
Kata kunci: ADA darah, HBD-2 feses, IFN-γ feses, IGRA, leukosit, PCR TB feses, TLR-2 feses, TLR-2 kolonosit tereksfoliasi.


Tuberculosis (TB) disease in Indonesia is still very high and ranks 2nd in the world in 2021. Difficulty in diagnosing intestinal tuberculosis (ITB) is due to the clinical manifestations of ITB disease which resemble other diseases, limited laboratory examinations, and invasive colonoscopy examinations, so it is necessary to develop a screening laboratory examination panel noninvasive with various laboratory biomarkers. This research is a cross-sectional study, aimed to obtain a screening panel for ITB diagnosis through fecal TB (Polymerase Chain Reaction) PCR test, hematology (leukocyte count, leukocyte type count, Lymphocyte to Neutrophil Ratio (LNR), Lymphocyte to Monocyte Ratio (LMR), and Erythrocyte Sedimentation Rate (ESR)), fecal Interferon-γ (IFN-γ), fecal Human BetaDefensin-2 (HBD-2), blood Interferon Gamma Releasing Assay (IGRA), and blood Adenosine Deaminase (ADA), fecal and exfoliated colonocytes Toll Like Reseptor-2 (TLR-2) expression. The research was conducted in Department of Internal Medicine, Gastrointestinal Endoscopy Center (GEC), Anatomical Pathology Laboratory, and Clinical Pathology Laboratory RSUPN Dr. Cipto Mangunkusumo Hospital (RSUPNCM) from November 2020−December 2022. Research subjects were adult patients suspected of ITB who underwent colonoscopy and histopathology laboratory examination, fecal TB PCR, hematology (leukocyte count, leukocyte type count, RNL, RML, and ESR), fecal IFN-γ, fecal HBD-2, blood IGRA, blood ADA, and TLR-2 expression of feces and exfoliated colonocytes. From 143 subjects suspected of having ITB, there were 22 ITB subjects and 121 Non-ITB subjects. There were no significant differences in leukocyte count, leukocyte type count, RNL, RML, IGRA positive proportion, fecal HBD-2 levels, fecal TLR-2 expression, and colonocyte TLR-2 expression in ITB and Non-ITB subjects. It was found that the proportion of positive fecal TB PCR, ESR, ADA, and IFN-γ levels were significantly higher in the ITB subject group compared to Non-ITB subjects. There was no significant difference in TLR-2 expression in feces and exfoliated colonocytes. The best cut-off, sensitivity, and specificity values were obtained for examination of blood ADA, fecal HBD-2, fecal IFN-γ, RNL, RML, and ESR. Model II (5 biomarkers) is recommended for clinician due to applicability, has passed internal validation, and inexpensive.
Key words: blood ADA, ESR, exfoliated colonocyte TLR-2, fecal HBD-2, fecal IFN-γ, fecal TB PCR, fecal TLR-2, IGRA, leukocyte.