CXCR3 chemokine receptor ligands in sarcoidosis

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...

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Autores principales:	N. M. Lazareva, O. P. Baranova, I. V. Kudryavtsev, N. A. Arsentieva, N. E. Liubimova, T. P. Ses’, M. M. Ilkovich, Areg A. Totolian
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2021
Materias:	sarcoidosis chemokines cxcl9 cxcl10 cxcl11 cxcr3 ligands peripheral blood plasma Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/0e74c93033564c2f88020c5119001f62
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id	oai:doaj.org-article:0e74c93033564c2f88020c5119001f62
record_format	dspace
institution	DOAJ
collection	DOAJ
language	RU
topic	sarcoidosis chemokines cxcl9 cxcl10 cxcl11 cxcr3 ligands peripheral blood plasma Immunologic diseases. Allergy RC581-607
spellingShingle	sarcoidosis chemokines cxcl9 cxcl10 cxcl11 cxcr3 ligands peripheral blood plasma Immunologic diseases. Allergy RC581-607 N. M. Lazareva O. P. Baranova I. V. Kudryavtsev N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich Areg A. Totolian CXCR3 chemokine receptor ligands in sarcoidosis
description	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.
format	article
author	N. M. Lazareva O. P. Baranova I. V. Kudryavtsev N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich Areg A. Totolian
author_facet	N. M. Lazareva O. P. Baranova I. V. Kudryavtsev N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich Areg A. Totolian
author_sort	N. M. Lazareva
title	CXCR3 chemokine receptor ligands in sarcoidosis
title_short	CXCR3 chemokine receptor ligands in sarcoidosis
title_full	CXCR3 chemokine receptor ligands in sarcoidosis
title_fullStr	CXCR3 chemokine receptor ligands in sarcoidosis
title_full_unstemmed	CXCR3 chemokine receptor ligands in sarcoidosis
title_sort	cxcr3 chemokine receptor ligands in sarcoidosis
publisher	SPb RAACI
publishDate	2021
url	https://doaj.org/article/0e74c93033564c2f88020c5119001f62
work_keys_str_mv	AT nmlazareva cxcr3chemokinereceptorligandsinsarcoidosis AT opbaranova cxcr3chemokinereceptorligandsinsarcoidosis AT ivkudryavtsev cxcr3chemokinereceptorligandsinsarcoidosis AT naarsentieva cxcr3chemokinereceptorligandsinsarcoidosis AT neliubimova cxcr3chemokinereceptorligandsinsarcoidosis AT tpses cxcr3chemokinereceptorligandsinsarcoidosis AT mmilkovich cxcr3chemokinereceptorligandsinsarcoidosis AT aregatotolian cxcr3chemokinereceptorligandsinsarcoidosis
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spelling	oai:doaj.org-article:0e74c93033564c2f88020c5119001f622021-11-18T08:03:50ZCXCR3 chemokine receptor ligands in sarcoidosis1563-06252313-741X10.15789/1563-0625-CCR-2181https://doaj.org/article/0e74c93033564c2f88020c5119001f622021-03-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/2181https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XSarcoidosis 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.N. M. LazarevaO. P. BaranovaI. V. KudryavtsevN. A. ArsentievaN. E. LiubimovaT. P. Ses’M. M. IlkovichAreg A. TotolianSPb RAACIarticlesarcoidosischemokinescxcl9cxcl10cxcl11cxcr3 ligandsperipheral bloodplasmaImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 23, Iss 1, Pp 73-86 (2021)

CXCR3 chemokine receptor ligands in sarcoidosis

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