scholarly journals Autoantibodies against central nervous system antigens in a subset of B cell–dominant multiple sclerosis patients

2020 ◽  
Vol 117 (35) ◽  
pp. 21512-21518 ◽  
Author(s):  
Stefanie Kuerten ◽  
Tobias V. Lanz ◽  
Nithya Lingampalli ◽  
Lauren J. Lahey ◽  
Christoph Kleinschnitz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
B Cell ◽  
Predictive Biomarker ◽  
Successful Outcome ◽  
Highly Active ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs). Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time. These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.

HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

2010 ◽  
Vol 16 (10) ◽  
pp. 1173-1177 ◽  
Author(s):  
M. Shahbazi ◽  
H. Ebadi ◽  
D. Fathi ◽  
D. Roshandel ◽  
M. Mohamadhosseni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Promoter Polymorphism ◽  
Exact Test ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Pcr Method ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients

2011 ◽  
Vol 18 (7) ◽  
pp. 1038-1041 ◽  
Author(s):  
Felipe von Glehn ◽  
Alessandro S Farias ◽  
Augusto C Penalva de Oliveira ◽  
Alfredo Damasceno ◽  
Ana Leda F Longhini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Oligoclonal Bands ◽  
Natalizumab Treatment ◽  
The Central Nervous System ◽  
Immunologic Abnormality ◽  
Csf Oligoclonal Bands ◽  
Multiple Sclerosis Patients

Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.

IsChlamydia pneumoniaepresent in the central nervous system of multiple sclerosis patients?

2000 ◽  
Vol 48 (3) ◽  
pp. 399-399 ◽  
Author(s):  
Servaas A. Morré ◽  
Corline J. A. De Groot ◽  
Joep Killestein ◽  
Chris J. L. M. Meijer ◽  
Chris H. Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients

Metallothionein expression in the central nervous system of multiple sclerosis patients

2003 ◽  
Vol 60 (6) ◽  
pp. 1258-1266 ◽  
Author(s):  
M. Penkowa ◽  
C. Espejo ◽  
A. Ortega-Aznar ◽  
J. Hidalgo ◽  
X. Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients

Human herpesvirus 6 infects the central nervous system of multiple sclerosis patients in the early stages of the disease

2004 ◽  
Vol 10 (4) ◽  
pp. 348-354 ◽  
Author(s):  
A Rotola ◽  
I Merlotti ◽  
L Caniatti ◽  
E Caselli ◽  
E Granieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Human Herpesvirus ◽  
Clinical Samples ◽  
Human Herpesvirus 6 ◽  
Early Stages ◽  
The Central Nervous System ◽  
Herpesvirus 6 ◽  
Multiple Sclerosis Patients

The presence and the replicative state of human herpesvirus 6 (HHV-6) were evaluated in clinical samples from multiple sclerosis (MS) patients at the first time of MS diagnosis. HHV-6 variant B was present in peripheral blood mononuclear cells of 5/32 (15%) patients, but persisted with a latent infection. Viral sequences were present also in cerebrospinal fluid (CSF), both free in the liquid (7/32, 22%) and latent in the cellular fraction (3/32, 9%), as shown by analysis of viral transcription. In these cases, variant A was detected. HHV-6 DNA sequences present in the CSF were associated to mature viral particles. In fact, in vitro infectious assays of CSF showed the presence of replication-competent virions. These results show that about 20% of MS patients have active foci of HHV-6 variant A infection in the early stages of the disease and suggest that viral replication takes place within the central nervous system.

Enhanced levels of IL-27 and IL-27R in the central nervous system of multiple sclerosis patients

2014 ◽  
Vol 275 (1-2) ◽  
pp. 173
Author(s):  
Vincent Sénécal ◽  
Diane Beauseigle ◽  
Raphael Schneider ◽  
Craig Moore ◽  
Alexandre Prat ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients
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