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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 82.5% 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 (p = 0.272, P = 0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Recently published data indicate that vitamin D abnormalities are common in sarcoidosis patients. The purpose of this study was to compare serum vitamin 25(OH)D levels among sarcoidosis patients with different clinical courses of the disease. The study also included the first observations on cognitive functions (i.e. depression and fatigue syndrome) in relation to vitamin D deficiency in sarcoidosis patients. At the Biochemical Laboratory of the Clinical Center of Serbia, Belgrade, vitamin D25(OH)D was measured using the Elecsys® Vitamin D total test. A total of 226 patients with biopsy-positive sarcoidosis were analyzed. The average median value of serum vitamin D was 9.47 mg/L, suggesting severe deficiency. Statistically significant correlation was found in patients with chronic disease and low levels of serum vitamin 25(OH)D (Chi-Square=6.044; df=2; p=0.014). The patient group with vitamin D serum levels higher than 20 mg/L showed higher levels of the mean forced vital capacity (FVC) by 380 mL, and forced expiratory volume in one second (FEV1) by 220 mL, when compared to the patient group with lower serum vitamin D. A statistically significant role was established for serum vitamin 25(OH)D levels as the predictor of fatigue (R2=0.878; p=0.038 (b=0.216)) and depression in patients with sarcoidosis (R2=0.80; p=0.000 (b=0.391)). The insufficiency of 25(OH)D seems to be an important factor in predicting the course of chronic disease, significant lung function impairments and cognitive failures such as fatigue and depression. The fact that the majority of the analyzed sarcoidosis patients had totally deficient serum 25(OH)D levels made this finding even more notable.