Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression

Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to da...

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Main Authors:	Giovannetti, Antonello, Maselli, Angela, Colasanti, Tania, Rosato, Edoardo, Salsano, Felice, Pisarri, Simonetta, Mezzaroma, Ivano, Malorni, Walter, Ortona, Elena, Pierdominici, Marina
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776852/

id	pubmed-3776852
recordtype	oai_dc
spelling	pubmed-37768522013-09-20 Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression Giovannetti, Antonello Maselli, Angela Colasanti, Tania Rosato, Edoardo Salsano, Felice Pisarri, Simonetta Mezzaroma, Ivano Malorni, Walter Ortona, Elena Pierdominici, Marina Research Article Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERβ, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular, the percentage of activated Treg (CD4+CD45RA− FoxP3brightCD25bright) was significantly higher in anti-ERα antibody positive patients than in anti-ERα antibody negative patients. Taken together our data clearly indicate that anti-ERα antibodies, probably via the involvement of membrane-associated ER, can represent: i) promising markers for SSc progression but, also, ii) functional modulators of the SSc patients’ immune system. Public Library of Science 2013-09-18 /pmc/articles/PMC3776852/ /pubmed/24058548 http://dx.doi.org/10.1371/journal.pone.0074332 Text en © 2013 Giovannetti et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Giovannetti, Antonello Maselli, Angela Colasanti, Tania Rosato, Edoardo Salsano, Felice Pisarri, Simonetta Mezzaroma, Ivano Malorni, Walter Ortona, Elena Pierdominici, Marina
spellingShingle	Giovannetti, Antonello Maselli, Angela Colasanti, Tania Rosato, Edoardo Salsano, Felice Pisarri, Simonetta Mezzaroma, Ivano Malorni, Walter Ortona, Elena Pierdominici, Marina Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
author_facet	Giovannetti, Antonello Maselli, Angela Colasanti, Tania Rosato, Edoardo Salsano, Felice Pisarri, Simonetta Mezzaroma, Ivano Malorni, Walter Ortona, Elena Pierdominici, Marina
author_sort	Giovannetti, Antonello
title	Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
title_short	Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
title_full	Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
title_fullStr	Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
title_full_unstemmed	Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression
title_sort	autoantibodies to estrogen receptor α in systemic sclerosis (ssc) as pathogenetic determinants and markers of progression
description	Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERβ, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular, the percentage of activated Treg (CD4+CD45RA− FoxP3brightCD25bright) was significantly higher in anti-ERα antibody positive patients than in anti-ERα antibody negative patients. Taken together our data clearly indicate that anti-ERα antibodies, probably via the involvement of membrane-associated ER, can represent: i) promising markers for SSc progression but, also, ii) functional modulators of the SSc patients’ immune system.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776852/
_version_	1612012585936224256

Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression

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