CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis.
CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis.
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DOI：
10.1186/1742-2094-11-18
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发表时间：
2014-01-29
影响因子：
9.3
通讯作者：
Weyenbergh JV
中科院分区：
文献类型：
--
作者：
Menezes SM;Decanine D;Brassat D;Khouri R;Schnitman SV;Kruschewsky R;López G;Alvarez C;Talledo M;Gotuzzo E;Vandamme AM;Galvão-Castro B;Liblau R;Weyenbergh JV
人类嗜T淋巴细胞病毒（HTLV-1）是导致失能性神经炎性疾病HTLV-1相关性脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）的病原体。目前，HAM/TSP中没有具有长期临床获益的疾病改善疗法或经验证的生物标志物用于临床随访。虽然CD 80和CD 86共刺激分子在免疫调节中起着重要作用，并反映了多发性硬化（MS）的疾病状态，但缺乏HAM/TSP的数据。使用流式细胞术，我们定量离体和体外表达的CD 80和CD 86在PBMC的健康对照，HTLV-1感染的个人和没有HAM/TSP，和MS患者。我们假设HAM/TSP和MS之间的离体CD 80和CD 86表达及其通过干扰素（IFN）-α/β的体外调节具有相似性，因此可能揭示HAM/TSP中的临床有用的生物标志物。在所有HTLV-1感染的个体中，T和B细胞中的CD 80和CD 86的离体表达增加，但在HAM/TSP中B细胞CD 86上调具有选择性缺陷。尽管总B细胞随着病程的增加而减少（p = 0.0003，r =-0.72），但在HAM/TSP中，CD 80 + B细胞与疾病严重程度呈正相关（p = 0.0017，r = 0.69）。B细胞CD 80表达在HAM/TSP女性中更高，强调免疫标记物可以反映在大多数自身免疫性疾病中观察到的女性优势。与MS患者相反，HAM/TSP患者中CD 80+（p = 0.0001）和CD 86+（p = 0.0054）淋巴细胞在体外培养时扩增。CD 80+和CD 86 + T细胞而非B细胞的扩增与HTLV-1感染中增殖增加相关。在体外用IFN-β治疗而不是IFN-α治疗导致健康对照组和神经炎性疾病患者的B细胞CD 86表达显著增加（HAM/TSP和MS），类似于MS中的体内治疗。我们提出了两种新的生物标志物，与疾病严重程度正相关的离体CD 80 + B细胞和优先由IFN-β诱导的CD 86 + B细胞，其恢复HAM/TSP中有缺陷的上调。这项研究表明B细胞在HAM/TSP发病机制中的作用，并为HAM/TSP中的B细胞靶向（在MS中具有已证实的临床获益）以及CD 80导向的免疫治疗开辟了途径，这在HAM/TSP和MS中都是前所未有的。
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. 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. 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. 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.
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影响因子：
2.3
作者：
da Silva, AJ;Brickelmaier, M;Hochman, PS
通讯作者：
Hochman, PS
DOI：
10.1128/cdli.11.6.1105-1110.2004
发表时间：
2004-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Brito-Melo, GEA;Souza, JG;Martins-Filho, OA
通讯作者：
Martins-Filho, OA
影响因子：
4.8
作者：
Domanski, P;Nadeau, OW;Colamonici, OR
通讯作者：
Colamonici, OR
影响因子：
4.6
作者：
Furukawa, Y;Bangham, CRM;Osame, M
通讯作者：
Osame, M
影响因子：
1.5
作者：
DETHE, G;BOMFORD, R
通讯作者：
BOMFORD, R