Rizzo Roberta, Pietrobon Silvia, Mazzoni Elisa, Bortolotti Daria, Martini Fernanda, Castellazzi Massimiliano, Casetta Ilaria, Fainardi Enrico, Di Luca Dario, Granieri Enrico, Tognon Mauro
Section of Microbiology and Medical Genetics, Department of Medical Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121, Ferrara, Italy.
Section of Pathology, Oncology and Experimental Biology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Fossato di Mortara, 44121, Ferrara, Italy.
J Transl Med. 2016 Jul 22;14(1):216. doi: 10.1186/s12967-016-0981-y.
Many investigators detected the simian polyomavirus SV40 footprints in human brain tumors and neurologic diseases and recently it has been indicated that SV40 seems to be associated with multiple sclerosis (MS) disease. Interestingly, SV40 interacts with human leukocyte antigen (HLA) class I molecules for cell entry. HLA class I antigens, in particular non-classical HLA-G molecules, characterized by an immune-regulatory function, are involved in MS disease, and the levels of these molecules are modified according with the disease status.
We investigated in serum samples, from Italian patients affected by MS, other inflammatory diseases (OIND), non-inflammatory neurological diseases (NIND) and healthy subjects (HS), SV40-antibody and soluble sHLA-G and the association between SV40-prevalence and sHLA-G levels.
ELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples.
The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of OIND (N = 8/77) and 15 % of NIND (N = 9/59), which is suggestive of a lower prevalence in respect to HS (22 %, N = 18/83). MS patients are characterized by higher sHLA-G serum levels (13.9 ± 0.9 ng/ml; mean ± St. Error) in comparison with OIND (6.7 ± 0.8 ng/ml), NIND (2.9 ± 0.4 ng/ml) and HS (2.6 ± 0.7 ng/ml) subjects. Interestingly, we observed an inverse correlation between SV40 antibody prevalence and sHLA-G serum levels in MS patients.
The data obtained showed a low prevalence of SV40 antibodies in MS patients. These results seems to be due to a generalized status of inability to counteract SV40 infection via antibody production. In particular, we hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides.
许多研究人员在人类脑肿瘤和神经疾病中检测到猿猴多瘤病毒SV40的踪迹，最近有研究表明SV40似乎与多发性硬化症（MS）有关。有趣的是，SV40通过与人类白细胞抗原（HLA）I类分子相互作用进入细胞。具有免疫调节功能的HLA I类抗原，特别是非经典的HLA - G分子，与MS疾病有关，并且这些分子的水平会根据疾病状态而改变。
我们对来自意大利的MS患者、其他炎症性疾病（OIND）患者、非炎症性神经疾病（NIND）患者及健康受试者（HS）的血清样本进行研究，检测其中的SV40抗体和可溶性sHLA - G，并探究SV40流行率与sHLA - G水平之间的关联。
采用酶联免疫吸附测定（ELISA）试验检测血清样本中的SV40抗体并定量sHLA - G。
在6%的MS患者（N = 4/63）、10%的OIND患者（N = 8/77）和15%的NIND患者（N = 9/59）中检测到SV40抗体，这表明与HS（22%，N = 18/83）相比，其流行率较低。与OIND患者（6.7±0.8 ng/ml）、NIND患者（2.9±0.4 ng/ml）和HS受试者（2.6±0.7 ng/ml）相比，MS患者的血清sHLA - G水平较高（13.9±0.9 ng/ml；平均值±标准误）。有趣的是，我们观察到MS患者中SV40抗体流行率与血清sHLA - G水平呈负相关。
获得的数据显示MS患者中SV40抗体的流行率较低。这些结果似乎是由于普遍无法通过产生抗体来对抗SV40感染。特别是，我们推测SV40的免疫抑制直接作用以及高水平免疫抑制性HLA - G分子的存在可能共同作用，损害B淋巴细胞对SV40特异性肽的激活。
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