Sarcoidosis, alveolar  -actin and pulmonary fibrosis

Cooke, Gordon; Govender, Praveen; Watson, Chris; Armstrong, Michelle E.; O’Dwyer, David N.; Keane, Michael P.; King, R; Tynan, Aisling; Dünn, Michael J.; Donnelly, Seamas C.

doi:10.1093/qjmed/hct160

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…Острое начало саркоидоза (синдром Лёфгрена), как правило, характеризуется достаточно благоприятным прогнозом. При хроническом течении саркоидоза также возможен благоприятный прогноз, однако при неблагоприятном течении активируются процессы фиброгенеза в пораженных органах [3,11,12,14,18,24]. Мы изучали уровни хемокинов CXCL9, CXCL10, CXCL11 в плазме крови больных с хроническим течением заболевания без признаков фиброзирования легочной ткани и с пневмофиброзом.…”

Section: Discussionunclassified

“…Оказалось, что концентрация хемокина CXCL9 у пациентов без признаков фиброза составила 4375,52 (2306,14-6036,84) пг/мл и была достоверно (р = 0,035) выше, чем у пациентов с пневмофиброзом 1839,88 (1156,61-3582,48) пг/мл. В экспериментальных работах на модели саркоидоза показано, что, в зависимости от режимов сенсибилизации животных, возможны разные исходы гранулемообразования: от полного обратного развития гранулематозных поражений до выраженного пневмофиброза, формирующегося вокруг гранулем, а также в перибронхиальных зонах [18,24]. Основную роль для благоприятного прогноза заболевания, по-видимому, играет генетически обусловленная способность организма к своевременной активации иммунорегуляторных процессов, минимизирующих возможность деструкции и последующего фиброзирования пораженной ткани.…”

Section: Discussionunclassified

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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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Section: Discussionunclassified

CXCR3 chemokine receptor ligands in sarcoidosis

et al. 2021

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“…Chemokines CCL17 and CCL22 contribute to ske wing towards M2-polarized macrophage phenotype exerting pro-fibrotic properties and expressing a whole set of cytokines and chemokines, including CCL17 and CCL22 [18,21]. The latter chemokines were examined in activating fibrogenesis both in experimental models and clinical practice in patients with sarcoidosis, idiopathic pulmonary fibrosis and some other diseases [7,12,13,18,21].…”

Section: Introductionmentioning

confidence: 99%

Chemokines Ccl17 and Ccl22 in Sarcoidosis

et al. 2021

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Various immune cells as well as related cytokines are involved in immunopathogenesis of sarcoidosis and mechanisms of granuloma development. Currently, a role for chemokines in sarcoidosis has been extensively investigated, which is paralleled with a search for key molecules necessary for recruiting immune cells to intrusion site and granuloma formation as well as affecting outcome of the latter. Our study was aimed for determining level of plasma CCL17/TARC and CCL22/MDC chemokines in patients with sarcoidosis who received no immunosuppressive therapy is of high priority for clarifying some aspects in underlying immunopathogenesis as well as seeking out for secure clinical and laboratory criteria for assessing activity and disease prognosis. 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: CCL17 – 78.24 pg/ml vs 26.24 pg/ml, p < 0.001; CCL22 – 660.60 pg/ml vs 405.00 pg/ml, p < 0.001. 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 CCL17 – 63% and 78%, CCL22 – 63% and 91%; in chronic sarcoidosis: CCL17 – 58% and 83%, CCL22 – 67% and 86%, respectively. In chronic sarcoidosis the levels of this chemokine correlated with the activity of angiotensin-converting enzyme (ACE), for CCL17 (r = 0.530; p = 0.003), for CCL22 (r = 0.446; p = 0.014). Patients with systemic lesions vs no systemic lesions (sarcoidosis of the respiratory system only) had significantly elevated CCL17 level: 102.82 pg/ml vs 32.72 pg/ml, p = 0.011. The concentration of chemokine CCL17 was significantly increased in patients with vs without signs of hepatomegaly: 130.73 pg/ml vs 51.60 pg/ml, p = 0.022. Levels of chemokines was significantly increased in patients with vs without ultrasound signs of splenomegaly comprising: for CCL17 – 249.18 pg/ml vs 46.87 pg/ml, p = 0.002; for CCL22 – 1271.40 pg/ml vs 660.63 pg/ml, p = 0.003. Thus, it should be noted that the peripheral blood plasma level of chemokines CCL17 and CCL22 may be used as additional prognostic markers in chronic sarcoidosis with varying scoring of clinical signs including with/without systemic disease manifestations.

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