Markers of Inflammation in Sarcoidosis: Blood, Urine, BAL, Sputum, and Exhaled Gas
Section snippets
Angiotensin-converting enzyme
Serum ACE activity has been used as a diagnostic and prognostic marker of sarcoidosis since Lieberman [17] revealed its elevation in patients with active disease in 1975. ACE is an acid glycoprotein (molecular weight 140,000 d) that converts angiotensin I into angiotensin II by cleaving the dipeptide histidine and leucine C-terminal of angiotensin I [17]. It is secreted by monocytes and macrophages and in sarcoidosis by pulmonary endothelial cells that release ACE into blood vessels where it
Lysozyme
Lysozyme, produced by the monocyte-macrophage system, is another enzyme that can be considered a potential marker of sarcoidosis severity. Enhanced activity of phagocytes in sarcoidosis may determine an increase in lysozyme in serum of these patients. This enzyme was first discovered in 1922 by Fleming who reported that it had antibacterial activity through cleavage of β1-4 glycoside bonds in cell walls of certain bacteria. Lysozyme is normally present in the granules of monocytes, macrophages,
Chitotriosidase
Chitotriosidase is a member of family 18 of glycosylhydrolases (or chitinases), enzymes involved in the degradation of chitin (an abundant polymer of N-acetylglucosamine) and chitin-like substrate [43]. The enzyme is expressed by activated macrophages and elevated activity has been observed in serum of patients with atherosclerosis, β-thalassemia, acute Plasmodium falciparum malaria, and visceral leishmaniasis, and in cerebrospinal fluid of patients with multiple sclerosis [44], [45], [46].
Cytokines and chemokines
Many cytokines and chemokines have been analyzed in serum and BAL of sarcoidosis patients [3], [54]; some of these mediators, together with immunocompetent cells, are involved in the inflammatory processes occurring in this disease and may have a potential clinical application (Box 1, Fig. 3) [1], [12]. They have been studied singly and in panels to evaluate Th1/Th2 profile. BAL seems to have the potential to provide useful diagnostic parameters; however, no single biochemical marker
Markers of oxidative stress
Oxidative stress is the result of an imbalance between oxidant and antioxidant molecules and may cause cell damage. Inflammatory cells, such as neutrophils and macrophages, release reactive oxygen species, such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, which act as oxidants during inflammatory processes, damaging neighboring cells [98]. Reactive oxygen species affect different cell components, such as cell membrane lipids, DNA, and proteins [98]. Oxidative stress can be
Other markers of sarcoidosis
Immunologic studies on serum, tissue, and BAL have highlighted a polyclonal hypergammaglobulinemia (with a predominance of IgG) in sarcoidosis patients [33], [57], [107] and formation of circulating immune-complexes [107]. Their clinical value, however, is poorly defined.
Other markers of inflammation have been analyzed in different human biologic fluids by different methods. For example, endothelin-1, a vasoactive bronchoconstrictive peptide involved in lung fibroproliferative processes, has
Proteomic approach
A more recent approach to the analysis of sarcoidosis markers is the application of proteomics. Proteome analysis enables one simultaneously to analyze all proteins present in a biologic sample and to define protein profiles characteristic of a disease [86], [123]. This approach is independent of any a priori hypothesis about specific proteins, implying high potential for new discoveries [86], [104], [124], [125], [126], [127], [128], [129], [130], [131], [132]. Many techniques with different
Summary
Sarcoidosis is characterized by intense inflammation at the different sites of localization full-stop. According to a recent classification, has also been included among autoinflammatory diseases [133]. Many different mediators, such as cytokines, chemokines, and other proteins with various functions, participate in its complex pathogenesis and some have been proposed as markers of inflammation. These generally increase during the active phase of the disease and they are considered markers of
Acknowledgments
The authors thank C. Madioni, C. Olivieri, and F, Mezzasalma for their contribution.
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