Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the connective tissues of the skin and of the internal organs. Several infectious agents, including human herpesvirus 6 (HHV-6), have been suggested as possible triggering factors, but a direct association between infection and SSc is still missing. Often, SSc patients display concomitant autoimmune thyroiditis signs, and an association between HHV-6 infection/reactivation and autoimmune thyroid diseases has been suggested by us and others. With the aim of investigating the possible association between HHV-6 infection and SSc, we characterized 20 SSc patients for the presence of HHV-6 in tissues and blood (by digital droplet specific PCR), as well as for the immune response against the virus. In addition, as endothelial cells (EC) are a target for HHV-6 infection and EC damage has a main role in the disease pathogenesis, we investigated the expression of factors associated with fibrosis in HHV-6 infected EC in vitro. The results showed HHV-6A presence at the skin level in all SSc subjects, with higher virus load associated with disease severity. By contrast, HHV-6B was detected at the blood level. SSc patients also displayed a higher frequency and titer of antibodies directed against the virus U94 gene, compared to controls, similar to what already observed in Multiple Sclerosis and Hashimoto's thyroiditis, two pathologies that have been associated with HHV- 6 infection. Furthermore, HHV-6 infection in vitro induces the expression of pro-fibrosis factors in EC. Our data suggest that virus infection/reactivation might be associated with the disease development and could be correlated to the progression of the disease at the tissue level, and open the way to future studies aimed to clarify the cellular immune response against the virus and understand the mechanisms by which HHV-6 might favor fibrotic transition in infected cells.
HHV-6 infection and systemic sclerosis: clues of a possible association
M. D’Accolti;I. Soffritti;E. Caselli
2019
Abstract
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the connective tissues of the skin and of the internal organs. Several infectious agents, including human herpesvirus 6 (HHV-6), have been suggested as possible triggering factors, but a direct association between infection and SSc is still missing. Often, SSc patients display concomitant autoimmune thyroiditis signs, and an association between HHV-6 infection/reactivation and autoimmune thyroid diseases has been suggested by us and others. With the aim of investigating the possible association between HHV-6 infection and SSc, we characterized 20 SSc patients for the presence of HHV-6 in tissues and blood (by digital droplet specific PCR), as well as for the immune response against the virus. In addition, as endothelial cells (EC) are a target for HHV-6 infection and EC damage has a main role in the disease pathogenesis, we investigated the expression of factors associated with fibrosis in HHV-6 infected EC in vitro. The results showed HHV-6A presence at the skin level in all SSc subjects, with higher virus load associated with disease severity. By contrast, HHV-6B was detected at the blood level. SSc patients also displayed a higher frequency and titer of antibodies directed against the virus U94 gene, compared to controls, similar to what already observed in Multiple Sclerosis and Hashimoto's thyroiditis, two pathologies that have been associated with HHV- 6 infection. Furthermore, HHV-6 infection in vitro induces the expression of pro-fibrosis factors in EC. Our data suggest that virus infection/reactivation might be associated with the disease development and could be correlated to the progression of the disease at the tissue level, and open the way to future studies aimed to clarify the cellular immune response against the virus and understand the mechanisms by which HHV-6 might favor fibrotic transition in infected cells.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
