Peripheral Blood Mononuclear Cell Immunophenotyping in Fibrodysplasia Ossificans Progressiva Patients: Evidence for Monocyte DNAM1 Up-regulation

Genny Del Zotto, Francesca Antonini, Irma Azzari, Claudio Ortolani, Gino Tripodi, Francesca Giacopelli, Serena Cappato, Lorenzo Moretta, Roberto Ravazzolo, Renata Bocciardi

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done.

METHODS: In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells.

RESULTS: We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA-DR molecules.

CONCLUSIONS: DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. © 2017 International Clinical Cytometry Society.

Original languageEnglish
Pages (from-to)613-622
Number of pages10
JournalCytometry Part B - Clinical Cytometry
Volume94
Issue number4
DOIs
Publication statusPublished - Jul 2018

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Myositis Ossificans
Immunophenotyping
Monocytes
Blood Cells
Up-Regulation
Heterotopic Ossification
Inborn Genetic Diseases
HLA-DR Antigens
Virus Diseases
Immune System
Adrenal Cortex Hormones
Vaccination
Cell Death
Mutation
Wounds and Injuries
Genes

Cite this

@article{c4fd97f025804727925dcf0d85f215d5,
title = "Peripheral Blood Mononuclear Cell Immunophenotyping in Fibrodysplasia Ossificans Progressiva Patients: Evidence for Monocyte DNAM1 Up-regulation",
abstract = "BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done.METHODS: In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells.RESULTS: We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA-DR molecules.CONCLUSIONS: DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. {\circledC} 2017 International Clinical Cytometry Society.",
author = "{Del Zotto}, Genny and Francesca Antonini and Irma Azzari and Claudio Ortolani and Gino Tripodi and Francesca Giacopelli and Serena Cappato and Lorenzo Moretta and Roberto Ravazzolo and Renata Bocciardi",
note = "{\circledC} 2017 International Clinical Cytometry Society.",
year = "2018",
month = "7",
doi = "10.1002/cyto.b.21594",
language = "English",
volume = "94",
pages = "613--622",
journal = "Cytometry Part B - Clinical Cytometry",
issn = "1552-4949",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Peripheral Blood Mononuclear Cell Immunophenotyping in Fibrodysplasia Ossificans Progressiva Patients

T2 - Evidence for Monocyte DNAM1 Up-regulation

AU - Del Zotto, Genny

AU - Antonini, Francesca

AU - Azzari, Irma

AU - Ortolani, Claudio

AU - Tripodi, Gino

AU - Giacopelli, Francesca

AU - Cappato, Serena

AU - Moretta, Lorenzo

AU - Ravazzolo, Roberto

AU - Bocciardi, Renata

N1 - © 2017 International Clinical Cytometry Society.

PY - 2018/7

Y1 - 2018/7

N2 - BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done.METHODS: In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells.RESULTS: We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA-DR molecules.CONCLUSIONS: DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. © 2017 International Clinical Cytometry Society.

AB - BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. However, an extensive expression profile of the peripheral blood mononuclear cells (PBMC) of FOP patients has never been done.METHODS: In this study, we carried out a wide PBMC immunophenotyping on a cohort of FOP patients and matching controls by multiparametric analysis of the expression of a panel of 37 markers associated with migration, adhesion, inhibition, activation, and cell death of circulating immune cells.RESULTS: We observed a statistically significant increase of the expression of DNAM1 receptor in patients' monocytes as compared to controls, and little but significant differences in the expression profile of CXCR1 (CD181), CD62L, CXCR4 (CD184), and HLA-DR molecules.CONCLUSIONS: DNAM1 had been previously shown to play a pivotal role in monocyte migration through the endothelial barrier and the increased expression detected in patients' monocytes might suggest a role of this surface receptor during the early phases of FOP flare-ups in which the activation of the immune response is believed to represent a crucial event. © 2017 International Clinical Cytometry Society.

U2 - 10.1002/cyto.b.21594

DO - 10.1002/cyto.b.21594

M3 - Article

C2 - 28985649

VL - 94

SP - 613

EP - 622

JO - Cytometry Part B - Clinical Cytometry

JF - Cytometry Part B - Clinical Cytometry

SN - 1552-4949

IS - 4

ER -