Abstract
BackgroundMany 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.ObjectiveWe 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.MethodsELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples.ResultsThe 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.ConclusionThe 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.
Highlights
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
The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of other inflammatory diseases (OIND) (N = 8/77) and 15 % of non-inflammatory neurological diseases (NIND) (N = 9/59), which is suggestive of a lower prevalence in respect to healthy subjects (HS) (22 %, N = 18/83)
We hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory human leukocyte antigen (HLA)-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides
Summary
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. 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. HLA-G has an important role in MS: (i) cerebrospinal fluid (CSF) levels and the intrathecal synthesis of sHLA-G are higher in MS patients in comparison with controls and are associated with clinical and radiological evidence of disease remission (ii) elevated sHLA-G concentrations in CSF correlated with the presence of an anti-inflammatory and pro-apoptotic intrathecal microenvironment, (iii) HLA-G expression is high within and around MS lesions and (iv) HLA-G + regulatory T cells highly represented in brain lesions of MS patients [8]
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