Chemokine receptor CXCR3 ligands in bronchoalveolar lavage fluid: associations with radiological pattern, clinical course, and prognosis in sarcoidosis

Piotrowski, Wojciech J.; Młynarski, Wojciech; Fendler, Wojciech; Wyka, Krystyna; Marczak, Jerzy; Górski, Paweł; Antczak, Adam

doi:10.20452/pamw.2349

Cited by 7 publications

(11 citation statements)

References 9 publications

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“…CXCL11 recruits immune cells, including CD4 + T helper cells, to sites of inflammation in response to local production of IFN-γ [8,34]. The potential relevance of this mechanism to sarcoidosis-associated granulomatous inflammation in the local environment has been suggested by previous studies showing that relative to healthy controls, sarcoidosis subjects have increased CXCL11 in bronchoalveolar lavage (BAL) fluid, alveolar macrophages, and lung tissue [12][13][14]. Our study takes this concept further by not only demonstrating that levels in the serum are also increased in sarcoidosis relative to health, but these serum levels also correlate with pulmonary disease manifestations.…”

Section: Discussionmentioning

confidence: 98%

“…Several studies have shown that protein and gene expression levels of CXCL9, CXCL10, and CXCL11 are increased in lung lavage or lung tissue in sarcoidosis subjects, suggesting a pathogenic role in the disease [12][13][14][15]. We have been interested in the potential for these chemokines to provide insights into sarcoidosis pathogenesis and to serve as informative biologic markers.…”

Section: Introductionmentioning

confidence: 99%

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Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Arger

Woodruff

et al. 2019

Respiratory Medicine

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Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects the lungs in 90% of patients, but has a wide range of disease manifestations and outcomes including chronic and progressive courses. Noninvasive biomarkers are needed to assess these outcomes and guide decisions for long term monitoring and treatment. Interferon-gamma (IFN-γ)inducible chemotactic cytokines (chemokines), CXCL9, CXCL10 and CXCL11, show promise in this regard because they have been implicated in the pathogenesis of and reflect the burden of granulomatous inflammation. CXCL11 has been reported to have unique functional properties in modulating adaptive immunity in model systems so our goal was to examine serum levels of CXCL11 in relation to clinical outcomes in a heterogeneous cohort of sarcoidosis subjects. Methods: CXCL19, CXCL10, and CXCL11 serum levels were measured in sarcoidosis and healthy subjects using ELISA assay. We determined relationships between CXCL11 and standard clinical inflammatory markers, expression of IFN-γ-related genes in whole blood, organ involvement, dyspnea scores, and measures of pulmonary function. Results: In a cross-sectional analysis of 104 sarcoidosis subjects, serum CXCL11 was significantly elevated compared to 49 healthy controls (p < 0.001). CXCL11 was positively correlated with CXCL9 and CXCL10 (p < 0.001), sedimentation rate (p < 0.01), and mean expression of three IFN-γ-related genes in whole blood (GBP1, STAT1, and STAT2) (p < 0.001). CXCL11 was inversely correlated with FVC %predicted (%pred) and FEV1 %pred and higher levels were associated with higher patient-reported dyspnea scores. We found positive correlations between CXCL11 and number of organs involved. Using survival analyses, we found that

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Serum CXCL11 correlates with pulmonary outcomes and disease burden in sarcoidosis

Arger

Woodruff

et al. 2019

Respiratory Medicine

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“…Хемокин CXCL9, как известно, способствует направленному движению клеток-эффекторов гранулемообразования в легкие из периферической крови [25,33,36,41,45]. Обнаруженное в настоящей работе пониженное содержание CXCL9 в плазме при активации процессов фиброзирования легочной ткани, вероятно, может свидетельствовать о снижении интенсивности гранулемообразования на этапе включения механизмов ремоделирования пораженной ткани и формирования пневмофиброза.…”

Section: Discussionunclassified

“…Целый ряд исследований посвящен изучению лигандов для CXCR3 при саркоидозе [11,12,21,33,36,45,46]. Это определяется тем, что, с одной стороны, именно клетки, экспрессирующие CXCR3, участвуют в формировании гранулем при саркоидозе, а с другой стороны, основным индуктором синтеза всех изученных лигандов CXCR3 является IFNγ, играющий важную патогенетическую роль в развитии иммунных ответов при заболевании.…”

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CXCR3 chemokine receptor ligands in sarcoidosis

et al. 2021

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Sarcoidosis is a polysystemic inflammatory disease of unknown etiology, morphologically related to the group of granulomatosis, with heterogeneous clinical manifestations and outcomes. Immune cells, in particular T helper cells, are attracted to lung tissue and/or other organs by chemokine gradients and play an important role in the granuloma formation. T helper cells migrate from peripheral blood to the tissues due to expression of CXCR3 chemokine receptor on their surface. It interacts, e.g., with CXCL9/MIG, CXCL10/IP- 10, and CXCL11/I-TAC. Our study was aimed for determining the levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC chemokines in peripheral blood of the patients with sarcoidosis, depending on the features of their clinical course before administration of immunosuppressive therapy. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 52). In 37% (19/52), they exhibited acute clinical manifestations, and 63% (33/52) had chronic sarcoidosis. The control group included peripheral blood samples from healthy volunteers (n = 22). The chemokine concentrations (pg/ml) were determined by multiplex analysis using xMAP technology (Luminex), and Milliplex MAP test system (Millipore, USA). In the patients with sarcoidosis, significantly higher levels of chemokines were shown relative to healthy volunteers: CXCL9, 4013.00 pg/ml vs 1142.00 pg/ml (p < 0.001); CXCL10, 565.90 pg/ml vs 196.60 pg/ml (p < 0.001); CXCL11, 230.20 pg/ml vs 121.10 pg/ml (p = 0.018). Plasma concentrations of CXCL9 and CXCL10 were significantly increased both in blood samples from patients with acute and chronic sarcoidosis compared to healthy volunteers, p < 0.001. The level of CXCL11 chemokine was significantly increased only in the patients with chronic sarcoidosis, compared to the healthy volunteers: respectively, 251.50 pg/ml and 121.10 pg/ml (p = 0.044). The levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), with r = 0.374; p = 0.042. The ACE level in sarcoidosis is considered a clinical and laboratory index of the disease activity. In acute sarcoidosis, the level of CXCL11 chemokine was not significantly higher than in healthy individuals, whereas the CXCL9 chemokine content was significantly increased and correlated with ACE activity (r = 0.762; p = 0.037). The level of CXCL9 chemokine was significantly decreased in patients with signs of fibrosis as compared with fibrosis-free patients (1839.88 pg/ml vs 4375.52 pg/ml, p = 0.035). Significantly higher levels of CXCL9 were detected in cases of systemic sarcoidosis, i.e. 6036.84 pg/ml, as compared with 1927.44 pg/ml in the patients without these signs (p = 0.018). Evaluation of clinical and laboratory diagnostic characteristics for plasma chemokine levels in sarcoidosis patients allowed to assess their sensitivity and specificity. The respective values were as follows: in acute sarcoidosis: for CXCL9, 84% and 95%; for CXCL10, 84% and 95%; for CXCL11, 74% and 59%. In chronic sarcoidosis, the respective values for CXCL9 were 82% and 72%; for CXCL10, 91% and 77%; for CXCL11, 79% and 55%, respectively. Thus, the determination of plasma CXCL9, CXCL10, and CXCL11 chemokines in sarcoidosis allows of understanding their role in development of the disease, e.g., recruitment of T helper cells from peripheral blood to the lung tissue, and granuloma formation. Clinical and immunological comparisons of CXCL9 levels in the peripheral blood of patients and characteristics of the clinical course of sarcoidosis indicate to the role of this diagnostic parameter for assessing the disease activity, signs of lung fibrosis, and systemic manifestations in this disease.

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“…Immunoangiostatic environment in sarcoidosis may also be confirmed by the studies showing the role of CXCR3 ligands (interferon inducible cytokines, such as IP-10, ITAC, and MIG). These cytokines are related to more severe and chronic course of sarcoidosis (Piotrowski et al 2014b). Apparently, the inconsistent rise in VEGF gene expression is the evidence of axis The progress in medical science and higher living standards have contributed to the increase life expectancy.…”

Section: Discussionmentioning

confidence: 99%