Comparative Evaluation of Serum Markers in Pulmonary Sarcoidosis

Miyoshi, Seigo; Hamada, Hironobu; Kadowaki, Toru; Hamaguchi, Naohiko; Ito, Ryoji; Irifune, Kazunori; Higaki, Jitsuo

doi:10.1378/chest.09-1975

Cited by 113 publications

(98 citation statements)

References 22 publications

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“…However, SARC patients presented with lower abundance of T cell-derived migration factors acting on monocytes and granulocytes compared with both TB patients and healthy controls. Previous reports have shown increased levels of sIL-2Ra in SARC (22). Although our data suggest a similar trend in both TB and SARC, differences were not statistically significant.…”

Section: Discussioncontrasting

confidence: 86%

Common patterns and disease-related signatures in tuberculosis and sarcoidosis

Maertzdorf

Weiner

Mollenkopf

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

301

308

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In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.G ene expression in peripheral blood cells from tuberculosis (TB) patients and healthy controls, both latently Mycobacterium tuberculosis-infected and uninfected, has been profiled by several groups in the recent past (1-7). Identified expression profiles indicate chronic activation of the immune system, with a marked activation of IFN signaling (3), proinflammatory signaling through the JAK-STAT pathway (5, 6), and elevated expression of Fc γ-receptors and their downstream response elements (2, 4). Although these biosignatures have been identified by several independent groups and possess the potential to discriminate latently M. tuberculosis-infected healthy individuals from active TB patients, the question remains whether these gene expression signatures are specific for TB or shared, at least in part, with diseases of similar pathology but distinct etiology.To address this question, we have conducted a comparative analysis of blood profiles in patients with active pulmonary disease manifestation of TB and sarcoidosis (SARC). The rational for choosing pulmonary SARC for such a comparison is the remarkable similarity in immune activation with active TB, suggesting a shared underlying pathophysiology (8). Although SARC is generally considered a noncommunicable disease of unknown etiology, patients with pulmonary involvement present with histological and ...

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Section: Discussioncontrasting

confidence: 86%

Common patterns and disease-related signatures in tuberculosis and sarcoidosis

Maertzdorf

Weiner

Mollenkopf

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

301

308

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“…As sarcoidosis is an inflammatory disease, it has been expected to observe increased values of hsCRP, ACE (11,12) and SAA compared to controls (13,14) and our results were in agreement with these findings (Table I). Increased concentrations of SAA may be a consequence of either increased production of proinflammatory cytokines that stimulate hepatic production of SAA (11) or activated cells in granulomas that also produce SAA (15).…”

Section: Discussionsupporting

confidence: 92%

Matrix metalloproteinases-9 and tissue inhibitor of matrix metalloproteinases-1 in sarcoidosis patients

Ivanišević¹,

Stefanović²,

Kotur‐Stevuljević³

et al. 2017

Arh farmaciju

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SummaryMatrix 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.

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“…These mechanisms result in elevated serum levels of KL-6 in active interstitial lung disease [9][10][11]. Therefore, KL-6 is a useful biological marker to evaluate the activity of interstitial lung disease [12][13][14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%