Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV- 6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

HHV-6A infection and systemic sclerosis: Clues of a possible association / Caselli, E.; Soffritti, I.; D'accolti, M.; Bortolotti, D.; Rizzo, R.; Sighinolfi, G.; Giuggioli, D.; Ferri, C.. - In: MICROORGANISMS. - ISSN 2076-2607. - 8:1(2020), pp. 8-39. [10.3390/microorganisms8010039]

HHV-6A infection and systemic sclerosis: Clues of a possible association

Giuggioli D.;
2020

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV- 6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.
2020
8
1
8
39
HHV-6A infection and systemic sclerosis: Clues of a possible association / Caselli, E.; Soffritti, I.; D'accolti, M.; Bortolotti, D.; Rizzo, R.; Sighinolfi, G.; Giuggioli, D.; Ferri, C.. - In: MICROORGANISMS. - ISSN 2076-2607. - 8:1(2020), pp. 8-39. [10.3390/microorganisms8010039]
Caselli, E.; Soffritti, I.; D'accolti, M.; Bortolotti, D.; Rizzo, R.; Sighinolfi, G.; Giuggioli, D.; Ferri, C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1226101
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