Marker Of Sarcoidosis Research Articles

Serial chitotriosidase measurements in sarcoidosis – Two to five year follow-up study

Chitotriosidase (CTO) is a human chitinolytic enzyme secreted by activated macrophages and polymorphonuclear neutrophils. Albeit not specific for sarcoidosis, it is increased in over 90% of patients with active disease. The aims of this study were to correlate CTO measurements with clinical assessment of sarcoidosis and to test CTO as a marker of sarcoidosis relapse. 95 patients were followed-up for 24-60 months. Serial CTO measurements were performed every 3-6 months and correlated to clinical symptoms, lung function (FVC and DLco) and chest X-ray. In 38 patients clinical outcome status (COS) at 5 years was determined. Initial CTO levels were significantly higher in patients with impaired FVC/DLco (p=0.011 for both) but there was no correlation with standard chest X-ray stages. Patients with Loefgren's syndrome had significantly lower initial and control CTO level compared to other patients (p=0.011 and p=0.001, respectively). At follow-up there was a positive correlation of CTO and deterioration of clinical symptoms (p<0.001), chest X-ray (p<0.001) and FVC/DLco (p=0.012 and p=0.086, respectively). Control CTO levels were significantly lower in no disease groups versus minimal or persistent disease group as defined by COS (p=0.003 and p<0.001, respectively). At relapse CTO increased for 100% or more from baseline value in 12/14 patients. It was shown that CTO correlates with certain sarcoidosis phenotypes (Loefgren's syndrome, COS) and that serial measurements of CTO correlate with clinical symptoms, chest radiographs and lung function.

Triggering receptor expressed on myeloid cells‐1 and 2 in bronchoalveolar lavage fluid in pulmonary sarcoidosis

Pulmonary sarcoidosis (PS) is characterized by the formation of granulomas in the lungs and has been associated with infection by microorganisms. Triggering receptor expressed on the surface of myeloid cells (TREM)-1 is overexpressed in response to infection while TREM-2 is involved in granuloma formation. We hypothesized that these receptors are overexpressed in PS and might be useful for diagnostic testing. Cell surface TREM-1 and TREM-2 expression in cells obtained at bronchoalveolar lavage (BAL) was measured in individuals with sarcoidosis (n = 26) and compared with that seen in individuals with other interstitial lung diseases (ILD) (n = 27). TREM-1 and TREM-2 expression was significantly increased in sarcoidosis compared with other ILD: total number of TREM-1, P = 0.0039 (23.81 vs 13.50 cells/μl), TREM-2, P < 0.0001 (32.81 vs 7.76 cells/μl); percentage of TREM-1: P = 0.0002 (41.30% vs 15.70%), TREM-2: P < 0.0001 (34% vs 9.60%); and mean fluorescence of TREM-1: P = 0.0005 (5.43 vs 1.96), TREM-2: P = 0.0011 (6.85 vs 2.77). Increase in both of these receptors seems to be typical for PS. In discriminating sarcoidosis from other ILD, the specificity (96%) and sensitivity (72%) of the combination of TREM-1 and TREM-2 was high. Increased TREM-1 and TREM-2 cell surface expression is observed in sarcoidosis. Evaluation of BAL cell expression of both of these receptors may serve as a diagnostic marker for sarcoidosis.

Chitotriosidase - a potential biomarker in sarkoidosis

Introduction. Sarcoidosis is a multisystem granulomatous disease, whose unpredictable course has prompted research into biomarkers useful to predict outcome. Discussion and Review of Literature. Chitotriosidase, a chitinase produced by activated macrophages, has recently been proposed as an indicator among the potential markers of sarcoidosis. Chitotriosidase is involved in the defense against pathogens containing chitin. Increased concentrations of chitotriosidase have been observed in a number of lysosomal storage diseases, such as Gaucher?s disease, fucosidosis, galactosialidosis, atherosclerosis, ?-thalassemia, Plasmodium falciparum-induced acute malaria, visceral leishmaniasis and more recently in the cerebrospinal fluid in patients suffering from multiple sclerosis. Serum chitotriosidase activity in patients with sarcoidosis was first evaluated by Grosso et al in 2004. The idea to detect the enzyme in sarcoidosis sprang from evidence of direct involvement of activated macrophages in the pathogenesis of sarcoidosis and granuloma formation. Serum chitotriosidase was tested as a biomarker at our department in 2011, when 217 sarcoidosis patients were examined. Serum chitotriosidase has proved to differentiate active from inactive form of the disease much better than angiotensin-converting enzyme, thus adding to its role in the diagnosis and prognosis of this disease. Conclusion. Chitotriosidase is a good biomarker of sarcoidosis with good sensitivity and specificity.

Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis

BackgroundSerum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. However, there remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis.MethodsWestern blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis.ResultsKL-6/MUC1 in BALF showed three bands and five band patterns. These band patterns were associated with the MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were dependent on molecular size class in BALF. Significantly increased levels of serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were observed in the subjects with influx of high molecular size KL-6/MUC1 from the alveoli to blood circulation. The multivariate linear regression analysis involving potentially relevant variables such as age, gender, smoking status, lung parenchymal involvement based on radiographical stage and molecular size of KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was significant independent determinant of serum KL-6 levels.ConclusionsThe molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum levels of KL-6 in sarcoidosis. This information may assist in the interpretation of serum KL-6 levels in sarcoidosis.

Diagnostic value of CD103 expression in bronchoalveolar lymphocytes in sarcoidosis

Pulmonary sarcoidosis is frequently characterized by a CD4(+)/CD8(+) ratio ≥3.5 in bronchoalveolar lavage fluid (BALF), although up to 40% of the cases present a normal or even decreased ratio, pointing out its variability and limitation as a diagnostic marker for sarcoidosis. Lung lymphocytes within the bronchial epithelium, the alveolar walls, and BALF express the integrin CD103. Our aim was to compare the expression of CD103 in BALF T-lymphocytes between sarcoidosis and other interstitial lung diseases (ILD) and to evaluate its relevance as a BALF diagnostic marker for sarcoidosis. A total of 86 patients with ILD (mean age±standard deviation, 42.6±16.6 years; 60.5% female), who underwent BALF as part of their initial diagnostic work-up, were enrolled into 2 groups: sarcoidosis (n=41) and other ILD (n=45). Area under the receiver operating characteristic (ROC) curve (AUC) was used to describe the performance of CD103 for sarcoidosis diagnosis. Sarcoidosis patients presented a significantly reduced CD103 expression in BALF T-lymphocytes, more pronounced in the CD4(+) subset. The BALF CD103(+)CD4(+)/CD4(+) ratio for a cutoff point of 0.45 was associated with a better diagnostic performance for sarcoidosis (AUC: 0.86 [95% confidence interval (95% CI): 0.78-0.94]; sensitivity: 81%; specificity: 78%), even for those with a CD4(+)/CD8(+) ratio <3.5 (AUC: 0.79 [95% CI: 0.64-0.93]; sensitivity: 75%; specificity: 78%). Assessment of CD103 expression in BALF CD4(+) T-lymphocytes may be a reliable tool for sarcoidosis diagnosis, independently of CD4(+)/CD8(+) ratio, pointing out the relevance of evaluating the CD103(+)CD4(+)/CD4(+) ratio in the ILD diagnostic work-up.

Value of s-ACE, BAL lymphocytosis, and CD4+/CD8+ and CD103+CD4+/CD4+ T-cell ratios in diagnosis of sarcoidosis

To the Editors: Sarcoidosis is one of the most common causes of idiopathic lung disease. The international standard for diagnosis of sarcoidosis is based on three criteria: 1) a compatible clinical and/or radiological presentation; 2) histological evidence of noncaseating granulomas; and 3) exclusion of other diseases that produce a similar histological or clinical picture [1]. The diagnosis of sarcoidosis is supported by an elevated CD4+/CD8+ T-cell ratio, bronchoalveolar lavage (BAL) lymphocytosis and elevated serum angiotensin-converting enzyme (s-ACE). However, these parameters are variable in sarcoidosis [2–4]. The integrin CD103 is expressed on CD4+ T-cells in BAL. Due to the high influx of circulating T-cells to the granulomata in sarcoidosis, a reduction in the fraction of BAL CD103+CD4+ T-cells has been suggested as a marker of sarcoidosis, in combination with lymphocytosis and CD4+/CD8+ ratio [5]. In selected groups of patients, decreases in the fraction of CD103+CD4+ T-cells are significantly associated with sarcoidosis [6,7]. The purpose of this study was to evaluate these parameters as diagnostic markers of sarcoidosis in consecutive patients in a tertiary hospital setting. The study included patients who underwent BAL with subsequent flow cytometric analyses at the Dept of Respiratory Medicine, Aarhus University Hospital (Aarhus, Denmark) from August 2007 until April 2009 (n=107). The descriptive parameters and paraclinical findings, including s-ACE (U·L−1), BAL lymphocytosis (determined by differential count), and CD4+/CD8+ and CD103+CD4+/CD4+ T-cell ratios …

Serum Chitotriosidase: A Potential Marker of Sarcoidosis Activity

PURPOSE: Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. The unpredictable clinical course of the disease has prompted research into biomarkers useful for predicting outcome. Among the potential markers of sarcoidosis, a recently proposed indicator was chitotriosidase, a chitinase produced by activated macrophages. In 2007 chitotriosidase activity was analyzed for the first time in a group of 96 patients with sarcoidosis in order to assess chitotriosidase specificity as a marker of sarcoidosis.((Bargagli E et al. Respiration 2007; 74: 548-552). In this study we wanted to evaluate value of chitotriosidase as a marker of sarcoidosis activity in our patients.

Functional variant ANXA11 R230C: true marker of protection and candidate disease modifier in sarcoidosis

In the recent genome-wide association study the polymorphisms of annexin A11 (ANXA11) gene were associated with susceptibility to sarcoidosis. Beside the replication of this finding and analysis of local ANXA11 expression in bronchoalveolar lavage cells, we wondered whether 'leading' ANXA11 rs1049550 (R230C) variant might also be related to the clinical manifestation of sarcoidosis. The study included 245 Czech patients with sarcoidosis and 254 healthy control subjects. The frequency of ANXA11(*)T allele was significantly lower in patients with sarcoidosis (35%) compared with controls (42%, P=0.04, odds ratio=0.77). Furthermore, ANXA11(*)T allele was less frequent in patients with the infiltration of lung parenchyma by comparison with those with isolated hilar lymphadenopathy (P=0.01). In line with the previous observation, ANXA11 mRNA expression was not deregulated in sarcoidosis and was independent from rs1049550 variant. In conclusion, ANXA11 rs1049550 single nucleotide polymorphism is the susceptibility marker in sarcoidosis, at least in Caucasians. Its role as a disease modifier should be independently replicated.

The potential of the immunological markers of sarcoidosis in exhaled breath and peripheral blood as future diagnostic and monitoring techniques

Sarcoidosis is characterised by non-caseating granulomatous inflammation, with exaggerated immune responses at sites of disease and derangements of normal tissue architecture. The lungs are most commonly involved and progressive inflammation may result in pulmonary fibrosis. The immunopathogenesis and aetiology remain uncertain, which has made it difficult to identify a single sufficiently sensitive or specific diagnostic marker. Further investigation is needed to identify sensitive and specific markers of disease, such as in peripheral blood and exhaled breath condensate (EBC). Identification of disease markers may also be useful for investigating disease activity and predicting progression to fibrosis. This review explores the literature on the cytokine profiles of blood and bronchoalveolar lavage lymphocytes following ex vivo stimulation, as well as disease markers measured using the medium of EBC.

Analysis of serum amyloid A in sarcoidosis patients

A crucial pathogenetic role of serum amyloid A (SAA) in granulomatous inflammation of sarcoidosis has recently been reported. In this study we analyzed SAA expression in detail, starting from proteomic analysis of serum of sarcoidosis patients. We also used the faster ELISA method that enabled us to examine a greater number of samples. Serum concentrations of SAA were significantly higher in sarcoidosis patients than controls (p<0.001), inversely correlated with FEV(1) and significantly higher in patients with subacute onset requiring prolonged and multiple steroid treatments (class 6 SCAC) than in patients with subacute onset not requiring therapy (class 4 SCAC) (p<0.001). Our results suggest that serum amyloid A could be a suitable marker of sarcoidosis: its serum concentrations are significantly higher in sarcoidosis patients than controls, the protein is only expressed in gels of sarcoidosis patients and not in healthy subjects, and the SAA1 isoforms could match the unidentified biomarker of sarcoidosis reported in a previous proteomic study by another group. The effectiveness of SAA as a clinical biomarker of sarcoidosis should now be investigated in a large prospective study.

Gastrointestinal: Rectal sarcoidosis due to paralytic ileus resembling adult‐onset Hirschsprung disease

A 37-year-old woman was referred to our hospital with refractory paralytic ileus. Previous abdominal CT scans from two months previously were normal, but the oral contrast medium remained in the bowel when the test was repeated. No organic obstruction of the small intestine was found by gastrograffin small bowel study. We tentatively diagnosed chronic idiopathic intestinal pseudo-obstruction (CIIP). However, gastroduodenal manometry revealed heterogeneous phase III activity from the second to third parts of the duodenum (visceral myopathy type), which made CIIP unlikely. Colonoscopy revealed no organic obstruction of the colon but there was rectal dilatation and extensive retention of stools. Biopsy specimens from the terminal ileum, ascending colon and the rectum were normal with no inflammation or dysplasia. Because of the finding of rectal dilation and weak colonic contraction a barium enema was performed for suspected adult-onset Hirschsprung disease. This revealed narrowing of the distal rectum (Fig. 1 arrow). Rectal manometry showed that the patient had no reflex contraction of the rectum despite anal dilatation with a balloon at 30 mmHg. These findings were compatible with Hirschsprung disease. To confirm the diagnosis, biopsy of all layers of the rectal wall was performed. Histological examination revealed numerous epithelioid cell granulomas (Fig. 2) involving the peripheral nerves and nerve plexuses of the muscular and the submucosal layers. Hyperplasia of acetylcholinesterase-positive fibers was not found in the lamina propria. Therefore, she was diagnosed as having rectal sarcoidosis with secondary paralytic ileus. There was no hilar lymphadenopathy, granular changes, or opacification on chest X-ray and CT scan. Angiotensin-converting enzyme, a marker of sarcoidosis, was normal at 10.5 (8.3–21.4) IU/L, but serum soluble IL-2receptor antibody was very high at 1,901 (135–483) pg/ml. Tuberculin skin test was negative (0 × 0/6 × 6 mm). Bronchoscopy revealed a mucosal reticular network that was compatible with sarcoidosis. The CD4/CD8 cell ratio was high (4.76) in the bronchial lavage fluid, but no granulomas were detected by transbronchial lung biopsy. We treated her for neurosarcoidosis with prednisolone at 60 mg/day. Her symptoms improved gradually, and she was discharged on oral prednisolone (30 mg/day). At that time, the mucosal reticular network had resolved on bronchoscopy. Narrow rectum (arrow) on barium enema with proximal recto-sigmoid dilatation. Epithelioid cell granulomas involving preipheral nerves and nerve plexuses of the muscular and submucosal layers (HE stain, magnification × 20). Sarcoidosis is a systemic disease that causes the formation of epithelioid granulomas. The incidence of symptomatic bowel obstruction due to sarcoidosis is 0.6%. However, all previous reported cases of bowel obstruction were from mechanical obstruction caused by sarcoid granulomas. A Pubmed search using the key words ‘sarcoidosis’ and ‘paralytic ileus’ from 1949 to 2009 did not reveal any previous publications on paralytic ileus induced by intramuscular sarcoid granulomas resembling adult-onset Hirschsprung disease. Contributed by

Exhaled 8-isoprostane as a prognostic marker in sarcoidosis. A short term follow-up

Background8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic value of this marker we tested whether: 1. high initial EBC 8-IP predispose to more severe disease; 2. low initial concentrations increase a chance of early remission; 3. remissions are connected with the decrease of EBC 8-IP.Methods40 patients (S) have been examined initially (V1) and after 8.5 ± 0.5 months (V2). EBC 8-IP concentrations were measured by ELISA. Chest X-ray, lung function test, serum ACE and Ca2+ concentrations, 24 hrs Ca2+loss, abdominal ultrasonography, symptoms evaluation were performed.ResultsWe confirmed higher concentrations of 8-IP in EBC of patients with sarcoidosis (p = 0.001). Relative risk (RR) of persistence of disease at V2 when initial 8-IP was above 20 pg/mL was 1.04, and the frequency distributions estimated by χ2 test were not significantly different. A chance (RR) of early complete remission when V1 8-IP was below DL, was 3.33 (p = 0.04 by χ2 test). A significant decrease of 8-IP at V2 was observed only in patients who received treatment (p = 0.03), but not in those with spontaneous remission.ConclusionsWe come to the conclusion, that low initial 8-IP may be a positive prognostic factor. A decrease of 8-IP in treated patients reflects a non-specific effect of treatment and is not related to mere regression of disease.

Levels of Transferrin in Bronchoalveolar Lavage Fluid in Sarcoidosis

There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. This study was designed to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 (range, 0.00-3.97) mg/dl, which was significantly higher compared with controls (0.36 (range, 0.00-1.02) mg/dl; p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 (range, 171- 383) mg/dl, which was significantly lower compared with controls (322 (range, 234-356) mg/dl; p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity.

Chitotriosidase activity in sarcoidosis and some other pulmonary diseases

Background: Patients with sarcoidosis have elevated levels of several markers of inflammation. Particularly high levels have been reported for chitotriosidase. In this study, we evaluate whether determining chitotriosidase in serum would be useful in the diagnosis and clinical management of patients with sarcoidosis. Methods: Patients with newly diagnosed sarcoidosis and patients with asthma, fibrosis, asbestosis, lung cancer or chronic obstructive pulmonary disease (n=190) were recruited from an outpatient department. Individuals with no disease (n=26) served as controls. An X-ray was taken, diffusion capacity was measured and blood samples were taken for analysis of chitotriosidase, soluble receptor for interleukin-2, tumour necrosis factor alpha and angiotensin converting enzyme. In most patients with sarcoidosis, the analyses were done before and after regular treatment with corticosteroids over 6 months. Results: Some patients with sarcoidosis had markedly high activities of chitotriosidase, but activities above controls were also found among patients with asbestos, fibrosis and lung cancer. There were significant relationships between chitotriosidase and interleukin-2 receptor and angiotensin-converting enzyme. After treatment, chitotriosidase activity decreased in 52 of 69 patients. Conclusions: The results confirm that chitotriosidase activity is markedly increased in some cases of sarcoidosis. As increased activities are also found in other diseases, chitotriosidase cannot be considered a specific marker of sarcoidosis. In cases of sarcoidosis where high CTO activities are found, this enzyme could serve as a useful marker supporting the diagnosis of sarcoidosis when following the effects of treatment and in surveillance for recurrence of the disease.

Chitotriosidase and soluble IL‐2 receptor: Comparison of two markers of sarcoidosis severity

Background. Sarcoidosis is a multisystemic granulomatous disease with an unpredictable clinical course characterized by accumulation of activated proliferating T lymphocytes and mononuclear phagocytes in affected organs. Aims and methods. The aims of this study were to describe the clinical, radiological and immunological features of a population of sarcoidosis patients followed at the Sarcoidosis Regional Centre in Siena and to analyse chitotriosidase and sIL‐2R concentrations in serum of these patients in order to understand their potential as disease markers. Results. Chitotriosidase and sIL‐2R concentrations in serum of sarcoidosis patients were found to be significantly higher than in healthy controls (p<0.01) and a positive correlation between the two markers was documented for the first time. Moreover, chitotriosidase and sIL‐2R were expressed differently in different radiographic stages of the disease. Conclusion. Chitotriosidase and sIL‐2R are two markers of sarcoidosis of different origin, the values of which show a correlation in these patients; they are easily detectable in serum and could be useful clinical markers of progression.

Clinical proteomics in chronic inflammatory diseases: A review

There is a need for better markers for the diagnosis and prognosis of chronic inflammatory diseases. Proteomic strategies can be helpful to detect new biomarkers. Proteomic analyses are performed to characterize the behaviour of the system rather than the behaviour of any single component. Since the genome has been unravelled, the proteome received more attention. Aim of this review was to focus on the use of different proteomics techniques to detect potential and/or common biomarkers in chronic inflammatory diseases. The identified and validated proteins detected in the different studies are compared and discussed to conclude if there are some common markers which can be used in the diagnosis and prognosis of the three chronic inflammatory diseases described in this study; multiple sclerosis, rheumatic diseases and lung inflammatory diseases. The heat shock protein family (hsp) was entitled as biomarkers with potential for further research in multiple sclerosis. Myeloid-related protein 8 (MRP-8) was found in three different rheumatoid arthritis (RA) studies with different sample materials and could be a potential marker for RA. α1-Antitrypsin was validated in two studies as a marker for sarcoidosis and α1-antitrypsin was also found to be a marker for cystic fibrosis (CF), together with myeloperoxidase and IgG.

HLA class II amino acid epitopes as susceptibility markers of sarcoidosis

Sarcoidosis is a multisystemic disorder of unknown etiology, affecting primarily the lung and characterized by epithelioid granulomas. Disease association studies showed human leukocyte antigen (HLA) class II to be related to sarcoidosis. Initially, we studied the association of sarcoidosis with DQB1, and in the present study, we evaluated all amino acid variants of the HLA-DPB1, -DQB1, -DRB1, -DRB3, -DRB4 and -DRB5 genes to identify possible polymorphisms associated with the disease. Patients and controls were typed for class II genes to the allele level by sequence-based typing. Multiple logistic regression models showed DRAla71 and DQPhe9 to be independently associated with the disease. Subdivision of patients according to their radiographic stage resulted in identification of DRArg74 as independent associated residue in the RS I group, whereas DRAla71 and DQTyr30 were associated with RS II-IV groups. Polymorphic residues specifically associated with sarcoidosis shed new light on the characteristics of sarcoidosis-triggered peptides. Overall, pocket 9 of DQ and pocket 4 of DR seem to be the most important areas involved in the association with sarcoidosis.

WITHDRAWN: Low CD4+ lymphocyte count in a non-HIV setting: A surrogate marker of sarcoidosis?

WITHDRAWN: Low CD4+ lymphocyte count in a non-HIV setting: A surrogate marker of sarcoidosis?

L’enzyme de conversion de l’angiotensine I (ECA) dans le diagnostic de la sarcoïdose

Angiotensin I-converting enzyme (ACE) is synthesized by sarcoidotic granulomas defining this enzyme as a diagnosis and prognosis marker of sarcoidosis. This granulomatous disease, a frequent disease with unknown aetiology, is essentially localized in lung and skin, but many other localizations are possible, as well as in nervous system. The diagnosis is based on a panel of clinical, biological and radiological arguments. Serum ACE has a particular interest although its sensitivity and specificity for sarcoidosis are not perfect; ACE can also help to follow this disease either spontaneously or after corticoid therapy. ACE can be measured in bronchoalveolar lavage fluid (BAL) where it better signs the activity of the pulmonary disease than in serum. ACE in cerebrospinal fluid (CSF), and eventually in other biological fluids, allows the diagnosis of sarcoidosis with extra-pulmonary locations. The methods for ACE activity determination are essentially based on the use of polypeptidic synthetic substrates. By varying their nature and the conditions for use various assays were developed for serum, plasma, BAL, CSF and other fluids where ACE can help. The data must be given in a critical manner in function of the actual knowledge on ACE gene, the enzymatic properties of the protein and the limits of sensitivity and specificity of the assays sometimes reserved to peculiar biological fluids.

Evaluation of Bronchoalveolar Lavage Fluid Phospholipids and Cytokine Release by Alveolar Macrophages as Prognostic Markers in Sarcoidosis

Background: The clinical course of sarcoidosis is unpredictable and reliable laboratory prognostic parameters are lacking. Objectives: The aim of the present study was to estimate the prognostic value of bronchoalveolar lavage fluid (BALF) phospholipids and cytokine production by alveolar macrophages (AM) in pulmonary sarcoidosis. Methods: We investigated BALF parameters in 64 subjects (55 patients with sarcoidosis and 9 healthy volunteers as controls). After a period of 12 months, the total sarcoidosis study population was divided into three groups according to radiological, functional and laboratory dynamics: the group with a favorable (n = 15), the one with an unfavorable (n = 16) and the one with an intermediate clinical course of the disease (n = 24). Results: The group of patients with a poor clinical outcome was characterized by a lower percentage of lymphocytes in BALF [20% (4–56%)], rather small amounts of cytokines [TNF-α: 1.5 ng/ml/10⁶(0.08–8.6), IL-6: 5.75 ng/ml/10⁶ (1.7–22.5)] and a significant decrease in BALF phospholipids [total lipid phosphorus (TLP): 29.9 µmol/l (13.8–68.3) as compared to 67.5 µmol/l (33.2–127.2) in controls]. Patients with a favorable clinical outcome were shown to have higher lymphocytosis (40%, range 6–64, p < 0.05 versus poor outcome), intensive TNF-α and IL-6 release by AM, and close to normal phospholipid content in BALF. Conclusions: The level of TNF-α secretion by AM <3.9 ng/ml/10⁶ and total lipid phosphorus in BALF less than 30 µmol/l may serve as markers of poor prognosis in pulmonary sarcoidosis.