dc.contributor.author |
Menezes, Soraya Maria |
|
dc.contributor.author |
Decanine, Daniele |
|
dc.contributor.author |
Brassat, David |
|
dc.contributor.author |
Khouri, Ricardo |
|
dc.contributor.author |
Schnitman, Saul V. |
|
dc.contributor.author |
Kruschewsky, Ramon |
|
dc.contributor.author |
López, Giovanni |
|
dc.contributor.author |
Alvarez, Carolina |
|
dc.contributor.author |
Talledo Albujar, Michael John |
|
dc.contributor.author |
Gotuzzo Herencia, José Eduardo |
|
dc.contributor.author |
Vandamme, Anne-Mieke |
|
dc.contributor.author |
Galvão-Castro, Bernardo |
|
dc.contributor.author |
Liblau, Roland |
|
dc.contributor.author |
Weyenbergh, Johan Van |
|
dc.date.accessioned |
2020-06-10T18:12:16Z |
|
dc.date.available |
2020-06-10T18:12:16Z |
|
dc.date.issued |
2014 |
|
dc.identifier.uri |
https://hdl.handle.net/20.500.12866/8080 |
|
dc.description.abstract |
Background: Human T-cell lymphotropic virus (HTLV-1) is the causative agent of the incapacitating, neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, there are no disease-modifying therapies with long-term clinical benefits or validated biomarkers for clinical follow-up in HAM/TSP. Although CD80 and CD86 costimulatory molecules play prominent roles in immune regulation and reflect disease status in multiple sclerosis (MS), data in HAM/TSP are lacking.Methods: Using flow cytometry, we quantified ex vivo and in vitro expression of CD80 and CD86 in PBMCs of healthy controls, HTLV-1-infected individuals with and without HAM/TSP, and MS patients. We hypothesized ex vivo CD80 and CD86 expressions and their in vitro regulation by interferon (IFN)-α/β mirror similarities between HAM/TSP and MS and hence might reveal clinically useful biomarkers in HAM/TSP.Results: Ex vivo expression of CD80 and CD86 in T and B cells increased in all HTLV-1 infected individuals, but with a selective defect for B cell CD86 upregulation in HAM/TSP. Despite decreased total B cells with increasing disease duration (p = 0.0003, r = -0.72), CD80+ B cells positively correlated with disease severity (p = 0.0017, r = 0.69) in HAM/TSP. B cell CD80 expression was higher in women with HAM/TSP, underscoring that immune markers can reflect the female predominance observed in most autoimmune diseases. In contrast to MS patients, CD80+ (p = 0.0001) and CD86+ (p = 0.0054) lymphocytes expanded upon in vitro culture in HAM/TSP patients. The expansion of CD80+ and CD86+ T cells but not B cells was associated with increased proliferation in HTLV-1 infection. In vitro treatment with IFN-β but not IFN-α resulted in a pronounced increase of B cell CD86 expression in healthy controls, as well as in patients with neuroinflammatory disease (HAM/TSP and MS), similar to in vivo treatment in MS.Conclusions: We propose two novel biomarkers, ex vivo CD80+ B cells positively correlating to disease severity and CD86+ B cells preferentially induced by IFN-β, which restores defective upregulation in HAM/TSP. This study suggests a role for B cells in HAM/TSP pathogenesis and opens avenues to B cell targeting (with proven clinical benefit in MS) in HAM/TSP but also CD80-directed immunotherapy, unprecedented in both HAM/TSP and MS. |
en_US |
dc.language.iso |
eng |
|
dc.publisher |
BioMed Central |
|
dc.relation.ispartofseries |
Journal of Neuroinflammation |
|
dc.rights |
info:eu-repo/semantics/restrictedAccess |
|
dc.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es |
|
dc.subject |
Adult |
en_US |
dc.subject |
Female |
en_US |
dc.subject |
Humans |
en_US |
dc.subject |
Male |
en_US |
dc.subject |
Middle Aged |
en_US |
dc.subject |
Gender |
en_US |
dc.subject |
Severity of Illness Index |
en_US |
dc.subject |
Sex Factors |
en_US |
dc.subject |
HTLV-I Infections |
en_US |
dc.subject |
human |
en_US |
dc.subject |
adult |
en_US |
dc.subject |
female |
en_US |
dc.subject |
male |
en_US |
dc.subject |
Multiple sclerosis |
en_US |
dc.subject |
multiple sclerosis |
en_US |
dc.subject |
article |
en_US |
dc.subject |
sex difference |
en_US |
dc.subject |
biological marker |
en_US |
dc.subject |
disease severity |
en_US |
dc.subject |
Cells, Cultured |
en_US |
dc.subject |
Leukocytes, Mononuclear |
en_US |
dc.subject |
Flow Cytometry |
en_US |
dc.subject |
HTLV-1 |
en_US |
dc.subject |
clinical article |
en_US |
dc.subject |
disease duration |
en_US |
dc.subject |
T lymphocyte |
en_US |
dc.subject |
autoimmune disease |
en_US |
dc.subject |
in vitro study |
en_US |
dc.subject |
human cell |
en_US |
dc.subject |
tropical spastic paraparesis |
en_US |
dc.subject |
flow cytometry |
en_US |
dc.subject |
B lymphocyte |
en_US |
dc.subject |
upregulation |
en_US |
dc.subject |
antigen expression |
en_US |
dc.subject |
peripheral blood mononuclear cell |
en_US |
dc.subject |
drug targeting |
en_US |
dc.subject |
CD86 antigen |
en_US |
dc.subject |
Paraparesis, Tropical Spastic |
en_US |
dc.subject |
Multiple Sclerosis |
en_US |
dc.subject |
Biological Markers |
en_US |
dc.subject |
ex vivo study |
en_US |
dc.subject |
beta interferon |
en_US |
dc.subject |
alpha interferon |
en_US |
dc.subject |
Antigens, CD80 |
en_US |
dc.subject |
Antigens, CD86 |
en_US |
dc.subject |
B cell |
en_US |
dc.subject |
B-Lymphocytes |
en_US |
dc.subject |
B7 antigen |
en_US |
dc.subject |
CD86 |
en_US |
dc.subject |
cell expansion |
en_US |
dc.subject |
Costimulatory CD80 |
en_US |
dc.subject |
Disease severity |
en_US |
dc.subject |
Ex vivo |
en_US |
dc.subject |
Human |
en_US |
dc.subject |
immunoregulation |
en_US |
dc.subject |
immunotherapy |
en_US |
dc.subject |
Interferon-alpha/beta |
en_US |
dc.subject |
lymphocyte proliferation |
en_US |
dc.subject |
Neuroinflammatory disease |
en_US |
dc.title |
CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis |
en_US |
dc.type |
info:eu-repo/semantics/article |
|
dc.identifier.doi |
https://doi.org/10.1186/1742-2094-11-18 |
|
dc.subject.ocde |
https://purl.org/pe-repo/ocde/ford#3.01.03 |
|
dc.subject.ocde |
https://purl.org/pe-repo/ocde/ford#3.02.25 |
|
dc.subject.ocde |
https://purl.org/pe-repo/ocde/ford#3.01.04 |
|
dc.relation.issn |
1742-2094 |
|