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. 2016 Nov 2;35(4):390-400.
doi: 10.1515/jomb-2016-0017. eCollection 2016 Oct.

Verifying Sarcoidosis Activity: Chitotriosidase versus ACE in Sarcoidosis - a Case-control Study

Spasoje Popević  1   2 , Zorica Šumarac  3 , Dragana Jovanović  1   2 , Dragan Babić  4 , Mihailo Stjepanović  2 , Snežana Jovičić  3   5 , Dragana Šobić-Šaranović  1   2 , Snežana Filipović  2 , Branko Gvozdenović  6 , Maja Omčikus  2 , Anđela Milovanović  7 , Jelica Videnović-Ivanov  2 , Ana Radović  3 , Vladimir Žugić  1   2 , Violeta Mihailović-Vučinić  1   2
Affiliations

Verifying Sarcoidosis Activity: Chitotriosidase versus ACE in Sarcoidosis - a Case-control Study

Spasoje Popević et al. J Med Biochem. .

Abstract
in English, Serbian

Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme - ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls.

Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis.

Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of .5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P < 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ =0.272, P =0.001).

Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Uvod: Do sada, nisu nađeni odgovarajući biomarkeri za procenu aktivnosti sarkoidoze. Ciljevi studije su bili: procena osetljivosti i specifičnosti dva već korišćena biomarkera aktivnosti sarkoidoze (serumskog angiotenzin-konvertujućeg enzima (ACE) i serumske hitotriozidaze) u populaciji od 430 bolesnika sa sarkoidozom. Ovi markeri su takođe analizirani u kontrolnoj grupi od 264 zdrava ispitanika.

Metode: Četiristo trideset bolesnika sa sarkoidozom koja je dokazana biopsijom podeljeno je u grupe sa aktivnom i neaktivnom bolešću i u grupe sa akutnom i hroničnom sarkoidozom. U podgrupi od 55 bolesnika, aktivnost sarkoidoze je procenjivana i F18 fluorodeoksiglukoznom pozitronskom emisionom tomografijom (18F-FDG-PET). Nivoi serumske hitotriozidaze i ACE nisu pratili normalnu distribuciju, tako da su u statističkoj analizi korišćeni neparametrijski testovi.

Rezultati: Nivoi serumske hitotriozidaze su skoro 6 puta bili viši kod bolesnika sa aktivnom sarkoidozom u odnosu na kontrolnu grupu i na bolesnike sa neaktivnom bolešću. Nivo serumske hitotriozidaze od 100 nmol/mL/h pokazao je osetljivost od 82,5% i specifičnost od 70,0%. Cut off vrednost od 32,0 U/L za aktivnost ACE u serumu pokazala je osetljivost od 66,0% i specifičnost od samo 54,0%. Statistički značajna povezanost je nađena između fokalne granulomatozne aktivnosti koja je detektovana pomoću 18F-FDG PET/CT i nivoa serumske hitotriozidaze, dok takva korelacija nije nađena sa ACE. Nivoi serumske hitotriozidaze su bili u značajnoj korelaciji sa trajanjem bolesti (P < 0,0001). Serumska hitotriozidaza je bila značajno povezana sa kategorijama kliničkog ishoda (COS) (ρ = 0,272, P = 0,001).

Zaključak: Aktivnost hitotriozidaze u serumu je dokazano pouzdan biomarker za procenu aktivnosti i hroniciteta sarkoidoze.

Keywords: biomarker; sarcoidosis; serum angiotensin converting enzyme; serum chitotriosidase.

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Conflict of interest statement

Conflict of interest statement The authors stated that they have no conflicts of interest regarding the publication of this article.

Figures

Figure 1
Figure 1
Box-plots graphs: A) Serum chitotriosidase in active sarcoidosis, inactive disease and healthy controls. B) Serum ACE values in healthy controls, patients with active and inactive disease.
Figure 2
Figure 2
Box-plots graphs: A) Serum chitotriosidase in acute versus chronic sarcoidosis and healthy controls. B) Serum ACE in healthy controls and sarcoidosis patients with acute and chronic disease.
Figure 3
Figure 3
ROC curve: serum chitotriosidase and serum ACE levels.
Figure 4
Figure 4
Box-plots graphs. The correlation of serum chitotriosidase level with the radiographic stage of lung sarcoidosis.
Figure 5
Figure 5
Serum chitotriosidase levels and sarcoidosis activity assumed on 18F-FDG PET/CT.
Figure 6
Figure 6
Disease duration and S-ACE levels and S-Chitotriosidase levels.
See this image and copyright information in PMC

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