© Borgis - Postępy Nauk Medycznych 3/2014, s. 150-153
Michał Szczepański1, Maciej Dądalski1, Edyta Szymańska2, Monika Meglicka1, Marek Woynarowski1, *Jarosław Kierkuś1
Stężenie kalprotektyny w stolcu jako dobry biomarker gojenia śluzówkowego w monitorowaniu przebiegu choroby u dzieci z nieswoistymi zapaleniami jelit
Fecal calprotectin is a good biomarker of mucosal healing in monitoring of children with IBD
1Department of Gastroenterology, Hepatology and Feeding Disorders, Children’s Memorial Health Institute, Warszawa
Head of Department: prof. Józef Ryżko, MD, PhD
2Department of Pediatrics, Nutrition and Metabolic Disorders, Children’s Memorial Health Institute, Warszawa
Head of Department: prof. Janusz Książyk MD,PhD
Streszczenie
Wstęp. Pacjenci z nieswoistymi zapaleniami jelit (IBD) mają dużo wyższe stężenie kalprotektyny w stolcu (FC) niż osoby zdrowe i chorzy z czynnościowymi chorobami jelit. Wykazano, że FC może być wykorzystana w diagnostyce różnicowej IBD, a także w monitorowaniu gojenia śluzówkowego u dorosłych pacjentów z IBD. Jednak nadal brak jest wystarczających danych oceniających ten marker u dzieci.
Cel pracy. Celem pracy jest ocena przydatności FC jako biomarkera gojenia śluzówkowego u dzieci chorych na IBD.
Materiał i metody. Do badania włączono 46 pacjentów (25 chłopców i 21 dziewczynek) w wieku 13,7 ± 3,8 lat chorujących na nieswoiste zapalenia jelit (24 na wrzodziejące zapalenie jelita grubego i 22 na chorobę Crohna). Wszyscy oni mieli wykonaną kolonoskopię i oznaczone w ciągu tygodnia przed badaniem stężenie kalprotektyny w stolcu. Endoskopowa ocena stanu zapalnego śluzówki opierała się na skali SES-CD w przypadkach choroby Crohna i skali Barona w przypadkach wrzodziejącego zapalenia jelita grubego. Całkowite wygojenie śluzówki było definiowane jako 0 punktów w skali SES-CD i 0 punktów w skali Barona. Dla oceny zdolności dyskryminacyjnej FC i optymalnych punktów odcięcia stężenia kalprotektyny w monitoringu wygojenia śluzówki wykorzystano analizę krzywych ROC.
Wyniki. Pole pod krzywą ROC (AUC) wyniosło 0,95. Optymalny punkt odcięcia różnicujący grupę chorych z całkowitym wygojeniem śluzówki od chorych z aktywnym zapaleniem wyniósł FC = 233 μg/g z czułością 1,0 i swoistością 0,79. Przy maksymalizacji swoistości natomiast punkt odcięcia wyniósł FC = 54 μg/g z czułością 0,77 i swoistością 0,97.
Wnioski. FC jest dobrym biomarkerem gojenia śluzówkowego w monitorowaniu przebiegu choroby u dzieci z nieswoistymi zapaleniami jelit. Stężenie kalprotektyny w stolcu poniżej 54 μg/g pozwala zidentyfikować 77% pacjentów z całkowitym wygojeniem śluzówki.
Summary
Introduction. Fecal calprotectin (FC) concentrations of patients with inflammatory bowel diseases (IBD) are much higher than those of healthy controls or patients with functional disorders or other gastrointestinal diseases. Thus FC is a good biomarker of gut inflammation in differential diagnosis of IBD as well as mucosal healing in monitoring of IBD in adults. There is shortage of data concerning predictive value of FC in mucosa status assessment in children with IBD.
Aim. The aim of the study was to assess the usefulness of FC as a biomarker of endoscopy proven mucosal healing in monitoring of children with IBD.
Material and methods. 46 patients (25M, 21F; aged 13.7 ± 3.8) with IBD (24 ulcerative colitis – UC, and 22 Crohn’s disease – CD) were involved to the study and had elective colonoscopy performed and FC within a week before endoscopy measured. Mucosa status during endoscopy were assessed with SES-CD in case of CD and with Baron score in case of UC. Full mucosal healing was defined as SES-CD = 0 or Baron score = 0. The ROC curves was used as a statistical method to establish cut off points and AUC (area under curve) was regarded as assessment of discrimination between subgroup with full mucosal healing vs. subgroup with mucosal inflammation present.
Results. The AUC was 0.95. The optimal cut-off level of discrimination between subgroup with full mucosal healing vs. subgroup with mucosal inflammation present was 233 μg/g with sensitivity 1 and specificity 0.79. When specificity was outweighed over sensitivity the cut-off point was 54 μg/g with sensitivity 0.77 and specificity 0.97.
Conclusions. FC is a good biomarker of mucosal healing in monitoring of children with IBD. Values below 54 μg/g enable to select 77% patients with full mucosal healing.
Introduction
Calprotectin is a calcium-binding protein with in vitro bacteriostatic and fungistatic properties. It is found in abundance in neutrophils, where it accounts for 60% of the protein in the cytosol. Lower calprotectin concentrations are found in monocytes and reactive macrophages (1, 2). Calprotectin is involved in the inflammatory process regulation. Study evidence has shown that its level is significantly increased in inflammatory bowel disease (IBD) and neoplasms, whereas normal values are found in patients with irritable bowel syndrome (IBS) and in healthy subjects (3, 4). Although, calprotectin is found in cerebrospinal fluid, colonic biopsies, saliva, plasma, synovial fluids, urine and faeces (5), only its fecal concentration (fecal calprotectin FC) seems to be an useful biomarker of intestinal inflammation, because, it is not influenced by extraintestinal inflammatory processes. Costa et al. (3, 4), proved that patients with clinically active IBD presented higher FC levels than those in remission or with quiescent disease. This highlighted FC as a promising non-invasive, cheep, and simple tool for predicting relapse and monitoring therapy. Study of Tibble et al. (6) showed strong correlation between FC levels and histopathologic findings in biopsies of IBD patients, and weak correlation with clinical condition expressed by CDAI (Crohn's Disease Activity Index), respectively. Other studies (7-9) proved that FC tends to correlate stronger with endoscopic activity than with aforementioned clinical indices. These results suggested that FC is useful not only in predicting relapse but also in monitoring mucosal healing, which is considered an endpoint for evaluation of efficacy in IBD treatment nowadays. However, there is shortage of data concerning predictive value of FC in mucosa status assessment, specially in children. The aim of the study was to assess the usefulness of FC as a biomarker of endoscopy proven mucosal healing in monitoring of children with IBD.
Aim
The aim of the study was to assess the usefulness of fecal calprotectin as a biomarker of endoscopy proven mucosal healing in monitoring of children with IBD.
Material and methods
Patients
46 patients (25M, 21F; aged 13.7 ± 3.8) with IBD (24 ulcerative colitis – UC, and 22 Crohn’s disease – CD) were involved to the study and had elective colonoscopy performed and FC within a week before endoscopy measured. Mucosa status during endoscopy were assessed with SES-CD in case of CD and with Baron score in case of UC. Full mucosal healing was defined as SES-CD = 0 or Baron score = 0. The ROC curves was used as a statistical method to establish cut off points and AUC (area under curve) was regarded as assessment of discrimination between subgroup with full mucosal healing vs. subgroup with mucosal inflammation present. Table 1 presents patients characteristics.
Table 1. Characteristics of study participants (n = 46).
Parameter | Characteristic |
Gender: – males – females | 25 (54.3%) 21 (46.7%) |
Age (years) | 13.7 ± 3.8 |
Type of IBD: – UC – CD | 24 (52.2%) 22 (47.8%) |
Methods
The level of fecal calprotectin was assessed with Bühlmann Quantum Blue Calprotectin test. It is an immunologic test which serves quantitive assessment of fecal calprotectin level. The test is a disposable cartridge which allows FC assessment within only about 45 minutes. After assessment, the outcome is registered with reader.
Quantum Blue Calprotectin is an immunologic test of double-binding which uses 2 types of mouse monoclonal antibodies (mAb) highly specific to human calprotectin. First of the antibodies (marked with colloid gold) is unchained and deposited within membrane in the distal part of the cartridge. After covering the membrane by properly prepared samples containing calprotectin’s molecules, the specific antibodies immediately bind the molecules and form complexes. These complexes quickly move along the cartrigde toward the test window, where constantly membrane bound antibodies bind them. The increased number of such gold marked complexes within small space become visible as a single line (testing Line). The intensity of this Line is proportional to the level of calprotectin within analyzed sample. Since the quantity of gold conjugeted antibody is in the number adequate to saturate calprotectin molecules within the sample, its excess (not calprotectin bound) moves forward along the cartridge reaching the point where goat anti-mouse antibody is deposited. This antibody binds all anti calprotectin antibodies forming the second single line (control line). The intensity of both lines is measured with Quantum Blue® Reader.
Statistics
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Piśmiennictwo
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