muramidase and Sarcoidosis--Pulmonary

We present a case of desquamative interstitial pneumonia (DIP) with elevated serum levels of angiotensin-converting enzyme and lysozyme, which are often found in sarcoidosis. After steroid therapy, improvements in the lung opacity and the serum lysozyme level were observed. Retrospective evaluation of four additional DIP cases showed that four of the five cases studied had an elevated serum lysozyme level. In an immunohistochemical analysis of the lung specimens, increased expression of lysozyme were found in the neutrophils and the alveolar macrophages. Elevated levels of serum lysozyme can occur in diseases such as DIP in which the neutrophil and macrophage activity may affect a patient's pathological condition.

Topics: Adrenal Cortex Hormones; Biomarkers; Biopsy, Needle; Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Follow-Up Studies; Humans; Idiopathic Pulmonary Fibrosis; Immunohistochemistry; Lung Diseases, Interstitial; Macrophages; Male; Middle Aged; Muramidase; Neutrophils; Peptidyl-Dipeptidase A; Radiography, Thoracic; Risk Assessment; Sarcoidosis, Pulmonary; Severity of Illness Index; Tomography, X-Ray Computed

Clinical appearance of sarcoidosis depends on the methods of case finding and geographical factors. In a further effort to clarify clinical characteristics of pulmonary sarcoidosis, we examined a larger population of consecutive pulmonary sarcoidosis cases throughout former West Germany and Switzerland.. In a prospective multicenter study from January 1982 to December 1984, 715 patients with newly-diagnosed pulmonary sarcoidosis were studied for their clinical appearance, roentgenological and laboratory findings and pulmonary function.. The group consisted of 366 male and 349 female patients with a median age of 33 years (range 14 to 76). 35% presented with roentgenological stage I disease, 51% with stage II and 14% with stage III. Extrapulmonary manifestations were found in 16%. Angiotensin converting enzyme was elevated in 62% of the cases. Lung function tests revealed a restrictive pattern in 19% and airway obstruction in 4%; 2% showed a combined ventilation disturbance. 66% of our patients were symptomatic in contrast to reports from former East Germany, a country with mass X-ray screening where only 18 to 35% of the patients presented with symptoms and 51 to 74% were in stage I.. Differences between our findings and data from East Germany underline the importance of case finding methods for the patterns of clinical appearance of sarcoidosis.

Topics: Adolescent; Adult; Aged; Diagnosis, Differential; Female; Follow-Up Studies; Germany, West; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prospective Studies; Radiography, Thoracic; Sarcoidosis, Pulmonary; Severity of Illness Index; Switzerland; Tuberculin Test

Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

Topics: Amyloidosis; Amyloidosis, Familial; Humans; Muramidase; Sarcoidosis; Sarcoidosis, Pulmonary

To compare the clinical characteristics of uveitic sarcoidosis in African American and non-African American patients with biopsy-proven sarcoidosis and to determine which diagnostic test results were most often suggestive of sarcoidosis in patients who were ultimately diagnosed as having the disease.. Retrospective review of consecutive patients with biopsy-proven sarcoidosis evaluated by the uveitis service between 1989 and 2009.. A total of 63 patients with uveitic sarcoidosis were identified: 39 (62%) were African American (P <.001) and 43 (68%) were female. African American patients presented at an earlier age (P <.001) and were more likely to have granulomatous anterior segment inflammation (P <.001). The levels of serum markers angiotensin-converting enzyme and lysozyme were elevated in 40% and 42% of patients tested, respectively. The levels of at least 1 marker were elevated in 18 patients (58%). Imaging study results were reported as consistent with sarcoidosis in 25 patients (69%) who underwent chest radiography and in 19 patients (100%) who underwent computed tomography.. In this series, African American patients were more likely to be diagnosed as having uveitic sarcoidosis and to present with uveitis if they were younger than 50 years. White patients were more likely to present when they were older than 50 years. A clinical picture that included granulomatous anterior segment inflammation was more common in African American patients. The use of serum markers (angiotensin-converting enzyme and lysozyme) positively identified more patients with biopsy-proven sarcoidosis when used in combination with appropriate chest imaging.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Black or African American; Female; Humans; Male; Mass Chest X-Ray; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Retrospective Studies; Sarcoidosis; Sarcoidosis, Pulmonary; Uveitis; Visual Acuity; White People; Young Adult

Although several serum markers have shown their ability to reflect lymphocytic alveolitis and disease progression in pulmonary sarcoidosis, to our knowledge no prior study has made comparative evaluations of these markers.. Forty-three patients with pulmonary sarcoidosis were enrolled. BAL fluid (BALF) cells were analyzed, and serum levels of serum amyloid A (SAA), soluble interleukin 2 receptor (sIL-2R), lysozyme, angiotensin-converting enzyme (ACE), and the mucin-like, high-molecular-weight glycoprotein KL-6 were measured at disease presentation. Clinical data, including chest radiographs, were collected at presentation and during follow-ups. Univariate and multivariate analyses were used to identify markers best predictive of increased parenchymal infiltration.. Significantly higher serum levels of sIL-2R, lysozyme, and KL-6 were found in patients with parenchymal infiltration compared with those without parenchymal infiltration. The numbers of total cells and lymphocytes in BALF were significantly higher in patients with parenchymal infiltration. Serum levels of sIL-2R, lysozyme, and KL-6 were significantly correlated with the numbers of total cells, lymphocytes, and CD4(+) T lymphocytes in BALF. At the cutoff levels determined by receiver operating characteristic curves, sIL-2R, lysozyme, KL-6 serum levels, and the number of BAL lymphocytes showed significant correlations with increased parenchymal infiltrations by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of increased parenchymal infiltration.. Our results suggest that initial serum sIL-2R, lysozyme, and KL-6 levels may reflect lymphocytic alveolitis in pulmonary sarcoidosis. Furthermore, initial serum KL-6 tends to associate with increased parenchymal infiltration in pulmonary sarcoidosis.

Topics: Adult; Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Bronchoscopy; Colorimetry; Disease Progression; Flow Cytometry; Follow-Up Studies; Humans; Latex Fixation Tests; Logistic Models; Luminescent Measurements; Male; Middle Aged; Mucin-1; Muramidase; Nephelometry and Turbidimetry; Peptidyl-Dipeptidase A; Radiography, Thoracic; Receptors, Interleukin-2; Respiratory Function Tests; Retrospective Studies; ROC Curve; Sarcoidosis, Pulmonary; Serum Amyloid A Protein; Statistics, Nonparametric

Pathogens such as mycobacteria and proprionibacterium have been implicated in the pathogenesis of sarcoidosis. alpha-Defensins (DF) are naturally occurring antimicrobial peptides. The aim of the present study was to assess whether DF are increased in the airway and/or systemic circulation in patients with pulmonary sarcoidosis and whether DF levels are related to sarcoidosis disease activity.. DF levels in plasma and BAL fluid (BALF) were measured in 30 patients with pulmonary sarcoidosis and in 10 controls. Plasma and BALF DF levels were compared according to disease activity. Molecular forms were analysed using reverse-phase (RP) HPLC to confirm plasma and BALF DF kinetics in pulmonary sarcoidosis.. DF concentrations in plasma and BALF were higher in patients with pulmonary sarcoidosis than in the controls. Plasma DF levels correlated with lysozyme but not with angiotensin-converting enzyme. These levels were high in patients in whom more organs were involved, whereas BALF DF levels were higher in patients at stage II or III than with those at sarcoidosis I. RP-HPLC showed high plasma levels of pro-defensins, DF precursors from the bone marrow, in sarcoidosis, although DF in peripheral neutrophils and BALF were the mature type.. High plasma DF concentrations resulted from bone marrow stimulation and seemed to be associated with disease activity, whereas BALF DF were released from accumulated neutrophils in the lungs and may contribute to parenchymal involvement in sarcoidosis.

Topics: Adult; Aged; alpha-Defensins; Bone Marrow; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Case-Control Studies; Female; Humans; Male; Middle Aged; Muramidase; Neutrophils; Peptidyl-Dipeptidase A; Sarcoidosis, Pulmonary

Nodular and reticular opacities were detected in both lower lung fields of a 75-year-old man in 2000. Bronchoscopy revealed pulmonary sarcoidosis. In 2002, nodular and reticular opacities were shown in the right upper lobe, and video-assisted thoracoscopic surgery was performed. The histological findings revealed usual interstitial pneumonia (UIP)-like lesions, whereas non-caseous granulomas were not detected. In the present case of pulmonary sarcoidosis, nodular and reticular opacities were predominantly distributed in both lower lung fields, and the histological findings obtained by video-assisted thoracoscopic surgery showed UIP-like lesions. These findings may enlighten the assist in understanding of the process of development of pulmonary sarcoidosis.

Topics: Aged; Antigens, Neoplasm; Bronchoalveolar Lavage Fluid; Glucocorticoids; Humans; Lung; Lung Diseases, Interstitial; Male; Mucin-1; Mucins; Muramidase; Peptidyl-Dipeptidase A; Prednisolone; Radiography; Sarcoidosis, Pulmonary; Thoracoscopy

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

Topics: Analysis of Variance; Biomarkers; Case-Control Studies; Cell Line; Enzyme-Linked Immunosorbent Assay; Epithelioid Cells; Female; Humans; Immunoglobulin Isotypes; Immunohistochemistry; Interferon-gamma; Interleukin-12; Lung; Lymph Nodes; Macrophages; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Radionuclide Imaging; Sarcoidosis, Pulmonary; Th1 Cells

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0. 05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases.

Topics: Clinical Enzyme Tests; Female; Humans; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Sarcoidosis, Pulmonary; Sensitivity and Specificity

Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, alpha-defensins are mainly bactericidal effectors in circulating granulocytes, beta-defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar lavage fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, alpha-defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway mucosa. In conclusion, the airway epithelium is protected by a complex antibacterial defense system. This is activated in sarcoidosis, and may explain why these patients seldom develop severe respiratory tract infections.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bronchoalveolar Lavage Fluid; Carrier Proteins; Cathelicidins; Defensins; Female; Granulocytes; Humans; Male; Middle Aged; Muramidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Sarcoidosis, Pulmonary

Topics: Biopsy; Eye Diseases; Humans; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis, Pulmonary; Surveys and Questionnaires

Interstitial lung diseases are characterised by the recruitment of mononuclear cells to disease sites where maturation occurs and activation products, including lysozyme (LZM), are released. Analysis of in vitro cell culture supernatants for activation products masks the functional heterogeneity of cell populations. It is therefore necessary to examine the secretion of activation products by single cells to assess whether the activation of newly recruited mononuclear phagocytes at the sites of disease in the lung is uniform and controlled by the local microenvironment.. The reverse haemolytic plaque assay was used to evaluate, at a single cell level, the ability of bronchoalveolar lavage (BAL) fluid from seven patients with sarcoidosis to activate Ficoll-Hypaque-separated peripheral blood mononuclear cells by comparison with BAL fluid from six normal volunteers and nine patients with systemic sclerosis. Monolayers of peripheral blood mononuclear cells and sheep red blood cells were cultured either alone or in the presence of 20% (v/v) BAL fluid with a polyclonal anti-LZM antibody. LZM/anti-LZM complexes bound to red blood cells surrounding the secreting cells were disclosed following complement lysis of red blood cells and quantification of plaque dimensions using microscopy and image analysis.. Bronchoalveolar lavage fluid from all the patients with sarcoidosis increased LZM secretion by peripheral blood mononuclear cells compared with unstimulated mononuclear cells. By contrast, BAL fluid from the other individuals had no effect on LZM secretion.. Single cells activated by BAL fluid can be evaluated by the reverse haemolytic plaque assay. BAL fluid from patients with sarcoidosis, but not from patients with systemic sclerosis or normal individuals, contains components capable of activating mononuclear phagocytes to secrete lysozyme.

Topics: Adult; Bronchoalveolar Lavage Fluid; Epithelium; Female; Hemolytic Plaque Technique; Humans; Immunoenzyme Techniques; Male; Middle Aged; Monocytes; Muramidase; Sarcoidosis, Pulmonary; Scleroderma, Systemic

Polyclonal elevation of immunoglobulins is classically described in sarcoidosis and could possibly be useful in the work-up of suspected sarcoidosis uveitis. Because exposure to viruses of the herpes group is high in all populations, determination of herpes serologies is probably suited for this purpose.. Therefore serum anti-herpes antibody patterns in sarcoidosis (SARC), HLA-B27 positive acute anterior uveitis (AAU), pars planitis (PP) and healthy age-matched controls were analysed. Frozen sera were analysed for exposure to CMV, HSV, VZV by ELISA IgG testing and to EBV-VCA by immunofluorescence. Complement fixing titers > or = 1/40 and an EBV-VCA titer > or = 1/1280 were considered elevated. For each patient exposed to 2 or more herpes viruses, a score made out of the number of elevated titers divided by the number of herpes viruses the patient was exposed to, was calculated and mean scores were compared using Student's t-test.. Mean score of patients with sarcoidosis was 0.47 +/- 0.27 (N = 18, mean age 60.2 +/- 21.4 years), significantly higher than AAU (N = 21; score 0.12 +/- 0.2; p < or = 0.000), than PP (N = 20; score 0.18 +/- 0.2; p < 0.003), and than age-matched healthy controls (N = 341, mean age 59 +/- 5.5 years; score = 0.15 +/- 0.14; p < 0.000).. Anti-herpes antibodies were found to be significantly elevated in sarcoidosis uveitis, suggesting that herpes serologies may be useful in the work-up of suspected ocular sarcoidosis, a disease for which sufficiently sensitive and specific tests are lacking.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Viral; Female; Herpesvirus 4, Human; Humans; Immunoglobulins; Keratitis, Herpetic; Male; Middle Aged; Muramidase; Sarcoidosis; Sarcoidosis, Pulmonary; Simplexvirus; Uveitis