Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis patients

1998 ◽  
Vol 4 (2) ◽  
pp. 49-54 ◽  
Author(s):  
P Ferrante ◽  
E Omodeo-Zorini ◽  
R Caldarelli-Stefano ◽  
M Mediati ◽  
E Fainardi ◽  
...  

JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), has been proposed as a possible aetiopathogenic factor in multiple sclerosis (MS). We performed a study to search the LT region of JCV genome by nested PCR in cerebrospinal fluid (CSF), peripheral blood mononuclear cell (PBMC) and urine samples collected from 121 MS patients, 24 patients with other neurological disorders (OND), 30 non neurological patients (NND) and in PBMCs and urine of 40 healthy subjects. JCV DNA has been found in the CSF of 11 MS patients (9%) while all the CSFs from the 24 OND and the 30 NND cases were negative. No significant differences have been observed as regard to the frequency of JCV DNA detection in PBMCs and urine between the MS patients and the control groups. Nucleotide sequences analysis of seven JCV CSF isolates showed that five strains were identical the prototypal strain, while the other two had a base mutation (T→C) in 4286 nucleotide (nt). The finding of JCV DNA in the CSF of MS patients suggest that JCV could play a role in the triggering and/or in the maintenance of MS aetiopathogenic process, and therefore it should be taken in consideration when monitoring this disease.

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandro Trentini ◽  
Massimiliano Castellazzi ◽  
Carlo Cervellati ◽  
Maria Cristina Manfrinato ◽  
Carmine Tamborino ◽  
...  

Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p<0.001andp<0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p<0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r=0.3,p<0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.


2003 ◽  
Vol 9 (3) ◽  
pp. 228-234 ◽  
Author(s):  
T Holmøy ◽  
B Vandvik ◽  
F Vartdal

Idiotopic sequences are created after V, D and J recombinations and by somatic mutations during affinity maturation of immuglobulin (Ig) molecules, and may therefore be potential immunogenic epitopes. Idiotope-specific T cells are able to activate and sustain the B cells producing such idiotopes. It is therefore possible that idiotope-specific intrathecal T cells could help maintain the persisting intrathecal synthesis of oligoclonal IgG observed in patients with multiple sclerosis (MS). This study was undertaken to examine T-cell responses to cerebrospinal fluid (CSF) IgG. Peripheral blood mononuclear cells (PBMC) from 14 of 21 MS patients and four of 17 control patients with other neurological diseases proliferated upon stimulation with autologous C SF IgG, while five and three, respectively, responded to serum IgG. By comparison, responses to myelin basic protein were recorded in only four MS and three control patients. Data from a limited number of patients indicate that the C SF IgG responsive cells were CD4+ and human leucocyte antigen DR restricted, that PBMC also respond to C SF IgG from other MS patients and that the C SF may contain T cells responding to autologous C SF IgG. This suggests that C SF IgG, or substances bound to this IgG, may represent T-cell immunogens, which could contribute to the intrathecal immune response in MS.


1998 ◽  
Vol 4 (2) ◽  
pp. 49-54 ◽  
Author(s):  
P. Ferrante ◽  
E. Omodeo-Zorini ◽  
R. Caldarelli-Stefano ◽  
M. Mediati ◽  
E. Fainardi ◽  
...  

2013 ◽  
Vol 261 (1-2) ◽  
pp. 123-128 ◽  
Author(s):  
Jerry Lin ◽  
Peggy Bettin ◽  
John K. Lee ◽  
Joseph K. Ho ◽  
Saud A. Sadiq

2008 ◽  
Vol 14 (8) ◽  
pp. 1056-1060 ◽  
Author(s):  
M Hirotani ◽  
C Maita ◽  
M Niino ◽  
SM Iguchi-Ariga ◽  
S Hamada ◽  
...  

Objectives DJ-1 plays a key role in the anti-oxidative stress function. Increasing evidence supports the role of oxidative stress in the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate whether the DJ-1 levels were increased in patients with MS and to examine its association with the progression of MS. Methods Quantitative immunoblot assays were performed to evaluate the DJ-1 level in serum and cerebrospinal fluid (CSF) collected from relapsing–remitting patients with MS ( n = 29), disease controls subjects ( n = 14), and healthy subjects ( n = 44). Results No significant difference was observed in the serum DJ-1 level among the patients with MS, disease controls, and healthy controls. However, the CSF DJ-1 levels were significantly higher in the patients with MS than in the disease control subjects ( P < 0.0001). A significant positive correlation was also found between the CSF DJ-1 levels and the Multiple Sclerosis Severity Score ( P < 0.005, r = 0.501). Conclusions These results show that the CSF DJ-1 levels are significantly increased in the CSF of patients with MS and that the CSF DJ-1 levels may be associated with the disease progression of MS. Therefore, DJ-1 possibly plays an important role in the pathogenesis of MS.


2007 ◽  
Vol 13 (5) ◽  
pp. 590-595 ◽  
Author(s):  
Roberto Alvarez-Lafuente ◽  
Marta García-Montojo ◽  
Virginia De Las Heras ◽  
Manuel Bartolomé ◽  
Rafael Arroyo

Objective To evaluate the possible involvement of JC virus (JCV) in the aetiology of multiple sclerosis (MS), through the comparison of DNA prevalences and viral loads of JCV in cerebrospinal fluid (CSF) of MS patients at the first demyelinating event and subjects suffering from other neurological diseases (OND). Methods Seventy-three CSF samples (43 from MS patients at the first demyelinating event, and 30 from patients with OND) were collected; all MS cases were followed up from 1 to 6.7 years after they were diagnosed with clinically definite MS. DNA was extracted and analysed by real-time PCR for the detection of JCV genomes. Results We found JCV DNA in the CSF of two MS patients (4.7%) with a mean viral load of 2.1 and 6.7 copies/mL of CSF. Among the patients of the OND group we did not find any positive sample. We did not find any difference in the course of the disease between MS patients with and without JCV genomes in their CSF along the follow up. Conclusion JCV seems to be only a bystander in the pathology of MS, and the presence of cell-free viral particles could be related to the immunological activation of the disease, mainly during relapses. Multiple Sclerosis 2007; 13: 590-595. http://msj.sagepub.com


1985 ◽  
Vol 31 (11) ◽  
pp. 1820-1823 ◽  
Author(s):  
O C Fagnart ◽  
C L Cambiaso ◽  
C J Sindic ◽  
P L Masson

Abstract A fetuin-like antigen was detected (smallest concentration detectable: 5 micrograms/L) by particle-counting immunoassay in 2% (13/641) of consecutive patients' sera but not in sera from 80 healthy blood donors, 40 neonates, or 40 pregnant women. The relation of the presence of detectable antigen to patients' diagnosis is not yet clear. However, in the group with cancer (154), it was found only in two of four patients with nephroblastoma and in three of five with tumors of tissue derived from the neurological crest: retinoblastoma (1/1), neuroblastoma (1/3), and medulloblastoma (1/1). Serum specimens from 422 patients with neurological disorders showed the antigen at a concentration greater than 5 micrograms/L in cases of neurosyphilis (5/11), peripheral neuropathy (12/38), Guillain-Barré syndrome (7/27), and multiple sclerosis (74/184). When we assayed 232 specimens of cerebrospinal fluid from the same neurological patients, we found the antigen in two cases of multiple sclerosis (6 and 15 micrograms/L) and in one case of Guillain-Barré syndrome (54 micrograms/L).


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