SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME

Atypical hemolytic uremic syndrom (aHUS) is a rare severe life-threatening form of thrombotic microangiopathy. aHUS is thought to be primarily mediated by dysfunctional complement regulation, due to mutations or genetic rearrangement of the complement components, or regulatory factors, as well as au...

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Autores principales:	T. E. Pankratenko, O. V. Moskalets, T. Yu. Abaseeva
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2018
Materias:	atypical hemolytic uremic syndrome children soluble adhesion molecules complement eculizumab remission Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6ddb4f90dd4a4159bc6cbc00b2a66176
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spelling	oai:doaj.org-article:6ddb4f90dd4a4159bc6cbc00b2a661762021-11-18T08:03:47ZSOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME1563-06252313-741X10.15789/1563-0625-2018-6-871-876https://doaj.org/article/6ddb4f90dd4a4159bc6cbc00b2a661762018-12-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1672https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XAtypical hemolytic uremic syndrom (aHUS) is a rare severe life-threatening form of thrombotic microangiopathy. aHUS is thought to be primarily mediated by dysfunctional complement regulation, due to mutations or genetic rearrangement of the complement components, or regulatory factors, as well as autoantibody production to the complement factors. These alterations promote uncontrolled complement activation by the alternative pathway on the surface of endothelial cells, followed by endothelial dysfunction, microthrombosis and organ damage, especially, renal pathology. Many studies showed that the biomarkers of endothelial activation/dysfunction including intercellular adhesion molecule type 1 (ICAM-1) and vascular cell adhesion molecule type 1 (VCAM-1) were associated with severe disease and could predict complications and clinical outcomes in different disorders. Increase of these biomarkers was observed in aHUS as well. Until recently, aHUS resulted in unfavorable outcomes, with high death rates in acute phase, and up to 2/3 patients progressed to the end-stage renal failure. Understanding the role of complement dysregulation in aHUS pathogenesis has led to major changes in therapeutic approaches. Eculizumab (a humanized anti-C5 monoclonal antibody) inhibits the terminal complement pathway. This drug has revolutionized treatment and improved prognosis in aHUS. Those patients who received eculizumab have shown sharp decreae in the C3 levels. However, the questions concerning duration of targeted therapy inremission still remains unclear.The aim of the present study was to evaluate serum С3, sICAM-1, sVCAM-1 levels in the children with aHUS remission supported by eculizumab maintenance treatment, or without it. Serum C3, sICAM-1 and sVCAM-1 levels were determined in 25 children with aHUS (14 treated with eculizumab and 15, without eculizumab). A control group included 17 children with a history of typical HUS. Serum levels of C3, sICAM-1 and sVCAM-1 were within normal age ranges in all the groups. The children treated with eculizumab showed decreased C3 levels (99±20 mg/l vs 112±15 mg/l, and 123±40 mg/l, respectively), and increased sICAM-1 levels (483±103 ng/ ml vs 343±50 ng/ml and 401±91 ng/ml, respectively) compared to other groups (p < 0.05). No differences in sVCAM-1 levels were revealed in the groups. Hence, no signs of subclinical complement activation or endothelial disfunction were revealed in the group free of eculizumab therapy. Normal C3, sICAM-1 and sVCAM-1 levels in blood indicate that normal endothelial state could be restored in aHUS, and this condition is maintained after discontinuation of the targeted therapy. Our results suggest that C3, sICAM-1 and sVCAM-1 monitoring may be useful for further management of these patients and for prediction of relapses.T. E. PankratenkoO. V. MoskaletsT. Yu. AbaseevaSPb RAACIarticleatypical hemolytic uremic syndromechildrensoluble adhesion moleculescomplementeculizumabremissionImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 20, Iss 6, Pp 871-876 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	atypical hemolytic uremic syndrome children soluble adhesion molecules complement eculizumab remission Immunologic diseases. Allergy RC581-607
spellingShingle	atypical hemolytic uremic syndrome children soluble adhesion molecules complement eculizumab remission Immunologic diseases. Allergy RC581-607 T. E. Pankratenko O. V. Moskalets T. Yu. Abaseeva SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
description	Atypical hemolytic uremic syndrom (aHUS) is a rare severe life-threatening form of thrombotic microangiopathy. aHUS is thought to be primarily mediated by dysfunctional complement regulation, due to mutations or genetic rearrangement of the complement components, or regulatory factors, as well as autoantibody production to the complement factors. These alterations promote uncontrolled complement activation by the alternative pathway on the surface of endothelial cells, followed by endothelial dysfunction, microthrombosis and organ damage, especially, renal pathology. Many studies showed that the biomarkers of endothelial activation/dysfunction including intercellular adhesion molecule type 1 (ICAM-1) and vascular cell adhesion molecule type 1 (VCAM-1) were associated with severe disease and could predict complications and clinical outcomes in different disorders. Increase of these biomarkers was observed in aHUS as well. Until recently, aHUS resulted in unfavorable outcomes, with high death rates in acute phase, and up to 2/3 patients progressed to the end-stage renal failure. Understanding the role of complement dysregulation in aHUS pathogenesis has led to major changes in therapeutic approaches. Eculizumab (a humanized anti-C5 monoclonal antibody) inhibits the terminal complement pathway. This drug has revolutionized treatment and improved prognosis in aHUS. Those patients who received eculizumab have shown sharp decreae in the C3 levels. However, the questions concerning duration of targeted therapy inremission still remains unclear.The aim of the present study was to evaluate serum С3, sICAM-1, sVCAM-1 levels in the children with aHUS remission supported by eculizumab maintenance treatment, or without it. Serum C3, sICAM-1 and sVCAM-1 levels were determined in 25 children with aHUS (14 treated with eculizumab and 15, without eculizumab). A control group included 17 children with a history of typical HUS. Serum levels of C3, sICAM-1 and sVCAM-1 were within normal age ranges in all the groups. The children treated with eculizumab showed decreased C3 levels (99±20 mg/l vs 112±15 mg/l, and 123±40 mg/l, respectively), and increased sICAM-1 levels (483±103 ng/ ml vs 343±50 ng/ml and 401±91 ng/ml, respectively) compared to other groups (p < 0.05). No differences in sVCAM-1 levels were revealed in the groups. Hence, no signs of subclinical complement activation or endothelial disfunction were revealed in the group free of eculizumab therapy. Normal C3, sICAM-1 and sVCAM-1 levels in blood indicate that normal endothelial state could be restored in aHUS, and this condition is maintained after discontinuation of the targeted therapy. Our results suggest that C3, sICAM-1 and sVCAM-1 monitoring may be useful for further management of these patients and for prediction of relapses.
format	article
author	T. E. Pankratenko O. V. Moskalets T. Yu. Abaseeva
author_facet	T. E. Pankratenko O. V. Moskalets T. Yu. Abaseeva
author_sort	T. E. Pankratenko
title	SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
title_short	SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
title_full	SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
title_fullStr	SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
title_full_unstemmed	SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME
title_sort	soluble adhesion molecules in children with hemolytic uremic syndrome
publisher	SPb RAACI
publishDate	2018
url	https://doaj.org/article/6ddb4f90dd4a4159bc6cbc00b2a66176
work_keys_str_mv	AT tepankratenko solubleadhesionmoleculesinchildrenwithhemolyticuremicsyndrome AT ovmoskalets solubleadhesionmoleculesinchildrenwithhemolyticuremicsyndrome AT tyuabaseeva solubleadhesionmoleculesinchildrenwithhemolyticuremicsyndrome
_version_	1718422358259138560

SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME

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