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.
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 (
F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis.
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
F-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 (
<0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (ρ=0.272,
=0.001).
Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.
Background
It has been reported that high‐density lipoprotein (HDL) particles have anti‐inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory ...and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis.
Materials and methods
Inflammatory high‐sensitive C‐reactive protein (hsCRP), angiotensin‐converting enzyme (ACE), SAA, lipid total cholesterol (TC), HDL‐cholesterol (HDL‐c), low‐density lipoprotein cholesterol (LDL‐c), triglycerides (TG) oxidative stress status parameters total oxidant status (TOS), malondialdehyde (MDA), pro‐oxidant–antioxidant balance (PAB), sulfhydryl (SH) groups and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects.
Results
HsCRP (P < 0·05), TC, LDL‐c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL‐c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration.
Conclusions
We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.
Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive oxygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in ...its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimination.
Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis patients and 90 controls.
Malondialdehyde, superoxide anion, total oxidant status, prooxidant–antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis.
Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development.
► Elevated serum and erythrocyte oxidative stress status were observed in sarcoidosis. ► Lipid status abnormality was noted in sarcoidosis. ► Serum and erythrocyte MDA strongly predict disease among oxidative stress markers. ► Serum oxidative stress parameters had the best discriminative potential. ► Connection between oxidative and lipid status may indicate risk for atherosclerosis.
Matrix metaloproteinases (MMPs) and their specific inhibitors - tissue inhibitors of matrix metalloproteinases (TIMPs) play an important role in pulmonary extracellular matrix destruction. ...Sarcoidosis is an inflammatory disease affecting multiple organs. It has been reported that MMP-9 and TIMP-1 levels were increased in bronchoalveolar lavage fluid and induced sputum of sarcoidosis patients. The aim of our study was to evaluate MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations and MMP-9/TIMP-1 ratio in sarcoidosis patients, their relationship with inflammatory markers and their ability do predict the existence of disease. We included 101 sarcoidosis patients and 50 healthy subjects. Serum samples were analyzed. Besides routine biochemical parameters, high-sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations were measured. MMP-9 (P<0.05), hsCRP, SAA and TIMP-1 (P<0.001) concentrations were significantly increased in patients whereas MMP-9/TIMP-1 complex was higher in patients, but with marginal significance. In sarcoidosis, TIMP-1 correlated significantly positively with inflammatory parameters (P<0.05). Uni-variate analysis showed that MMP-9, TIMP-1, hsCRP and SAA had the ability to predict the existence of sarcoidosis. In the model consisted of MMP- 9, TIMP-1, hsCRP and SAA, only SAA remained significant predictor of disease (P<0.01). Results showed the significance of MMP-9 and TIMP-1 in sarcoidosis.
Fatigue in sarcoidosis: detection and treatment Vucinic, Violeta; Stojkovic, Mirjana; Milenkovic, Branislava ...
Srpski arhiv za celokupno lekarstvo,
2012 Jan-Feb, 2012-00-00, 20120101, 2012-01-01, Letnik:
140, Številka:
1-2
Journal Article
Odprti dostop
Fatigue is a prominent symptom in a large number of medical conditions, malignant and infectious diseases. Fatigue is also a prominent symptom of sarcoidosis. The occurrence of fatigue in sarcoidosis ...is well known but exact incidence has not been established and varies from 30-70% of patients depending on age, sex and organ involvement by the granulomatous process. The exact definition of fatigue varies broadly. It can be both physical and mental. The patients describe their sensation of fatigue qualitatively different from that fatigue they experienced before they became sick. Fatigue has a major impact on the quality of life in sarcoidosis. Establishing the extent of fatigue in sarcoidosis provides relevant insight regarding the patient's quality of life. Unfortunately there is no objective parameter for assessing fatigue in sarcoidosis. Generally, fatigue is detected by means of questionnaires. Regarding the therapy, there is no effective treatment for fatigue in sarcoidosis.
The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United ...States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country.
This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status.
The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate.
The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.
Sarcoidosis is a multisystemic disease of unknown etiology. Genetic factors play a considerable role in the onset of the disease. Tumor necrosis factor alpha (TNF-a) is a proinflammatory cytokine ...which plays an important role in the pathogenesis of the disease and the formation of granuloma by regulating cellular proliferation and apoptosis.
The aim of this study was to investigate the role of TNF-alpha-308 G/A polymorphism in the development of sarcoidosis and to evaluate the association between the aforementioned type of polymorphism and the clinical course of the disease.
Seventy patients with sarcoidosis and 50 healthy volunteers were genotyped for the TNF-alpha-308G/A polymorphism. Polymorphism variants were examined by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) on the DNA isolated from blood leukocytes.
There were no significant differences in TNF-alpha-308A allele frequency distribution between sarcoidosis patients and the control group, but the TNF-alpha-308A allele was observed significantly more frequently in the sarcoidosis patients with Löfgren's syndrome when compared with non-Löfgren's patients.
We have found that the TNF-alpha-308A variant is associated with Löfgren's syndrome in Serbian patients with sarcoidosis.
The role of vitamin D in multisystem sarcoidosis Mihailović-Vučinić Violeta; Ignjatović Svetlana; Dudvarski-Ilić Aleksandra ...
Journal of medical biochemistry,
10/2012, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
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.
In diagnostics of neurosarcoidosis, radiological diagnostic procedures are available, non-invasive and they contribute significantly to the diagnosis of this disease. The aim of this paper is to ...present a brief overview of the radiological diagnostic methods, their application, and their importance in daily clinical work with these patients. RADIOLOGICAL PRESENTATION OF NEUROSARCOIDOSIS: Magnetic resonance is the method of choice in diagnostics of this disease. Computed tomography can also be helpful in patients with contraindications for magnetic resonance, although it is less precise in assessing the involvement of the periventricular white matter, hypothalamus, and cranial nerves. The number of lesions and the degree of involvement of the parenchyma and leptomeninges are better seen by magnetic resonance than by computed tomography scan. It is important to note that the magnetic resonance imaging may be normal in patients with neurosarcoidosis, especially in patients with cranial neuropathy, or in patients treated with corticosteroids. There is a number of variability in the occurrence of neurosarcoidosis on radiological images.
Radiological procedures are on the very top of diagnostic pyramid of this disease due to their availability, non-invasiveness, and precision.
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