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Krooniset bakteeri-infektiot (Luettu 193806 kertaa)
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Re: Krooniset bakteeri-infektiot
Vastaus #300 - 20.12.2016 - 15:58:58
 
Antivirus immune activity in multiple sclerosis correlates with MRI activity.

https://www.ncbi.nlm.nih.gov/pubmed/25939660

Jan 2016

OBJECTIVE:
The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging.

METHODS:
Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays.

RESULTS:
We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later.

CONCLUSIONS:
We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.
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Re: Krooniset bakteeri-infektiot
Vastaus #301 - 20.12.2016 - 16:09:50
 
Aetiology: Neighbourhood watch

http://www.nature.com/nature/journal/v540/n7631_supp/full/540S4a.html?cookies=ac...

Emerging evidence points to a viral infection, low levels of vitamin D and genetics as culprits in multiple sclerosis, but how they combine to cause the disease is unclear.
*******
Canada has the highest rate of MS in the world, with 291 cases per 100,000 people2. But rates vary widely from one region of Canada to another3, 4, 5. Several studies have concluded that something in the environment in Canada is contributing to MS — indeed, rates of MS in immigrants to Canada quickly rise to approach Canadian levels6, 7.

Differences between countries can suggest possible causes. Clusters in particular neighbourhoods, such as those in Ottawa and Winnipeg, raise suspicion about local environmental factors, including outbreaks of infectious disease or genetic differences in multicultural cities, says Mahmoud Torabi, a statistician at the University of Manitoba and an author of the Winnipeg study.

   “The body of evidence is difficult to get a grip on, it's so huge.”

Until recently, researchers could not pinpoint why Canada in general, and specific places in particular, are so rife with this neurodegenerative disease6, 7, 8. But an international research effort — including database analyses, epidemiology, microbiology, genetics and immunology — is now yielding a growing body of evidence on the causes of MS. “It's difficult to get a grip on, it's so huge,” says Egil Røsjø, a neurologist at Akershus University Hospital near Oslo, who is also completing a doctorate on MS aetiology. “There are lines of evidence that are pointing more or less in the same direction from all these different angles.”

And they are pointing to three main culprits: Epstein–Barr virus (EBV), which is a herpesvirus that causes mononucleosis (glandular fever); low levels of vitamin D; and genetic variants that increase susceptibility to MS.
******
There are three broad theories to explain how EBV infection could result in MS, explains Bar-Or. One possibility is that the EBV infects the central nervous system (CNS), especially the brain. The virus may then kill oligodendrocytes, the cells that produce the myelin sheath — the insulating envelope that coats the nerve fibres (axons). Myelin speeds up the nerve impulses travelling through the axons and is essential for normal nerve function.

In the CNS, the infection may also trigger an immune response in which a type of immune cell known as CD8 tries to kill the virus but also damages oligodendrocytes and neurons. Bar-Or admits that this theory is controversial, because although some researchers have found the virus in the CNS, others have been unable to replicate the finding.

A second theory involves molecular mimicry, in which the immune system, Bar-Or says, may mistake myelin basic protein (MBP), which is important for the myelination process, for a similar piece of the invading EBV. The immune system's T cells have receptors that can recognize both the virus and MBP, and when the T cells are activated during the immune response to the virus, they could attack MBP as well as EBV in parts of the brain, resulting in a loss of myelin.

A third possible mechanism involves immune cells known as B cells. In normal immune responses, there are interactions between B cells, myeloid cells and T cells when responding to invading bacteria and viruses, and reversing the immune response when it is no longer needed. Any imbalance in this delicate dance can cause a strong or long-term response that goes beyond its original purpose and injures the body by interfering with basic cell functions, says Bar-Or. Perhaps EBV causes such an imbalance in MS by activating the B cells that they no longer perform their crucial regulatory functions, but instead start to promote inflammation. There is some support for this theory because MS treatments that remove B cells have succeeded in decreasing MS relapses, says Bar-Or.
*********
The mounting evidence of the link with vitamin D has sparked discussion about how low levels could lead to MS. Bar-Or points out that vitamin D has been shown to affect the immune response in many of the cell types involved in MS, including myeloid, B and T cells. “There's an enormous amount of literature that associates vitamin D deficiency with risk of disease,” adds Richards.
*******
“The genetic contribution doesn't explain even half the risk,” cautions Bar-Or, so it may be possible to prevent the disease by targeting the environmental factors involved.

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Re: Krooniset bakteeri-infektiot
Vastaus #302 - 24.12.2016 - 00:51:27
 
Role of Therapeutic Plasma Exchange in Treatment of Tumefactive Multiple Sclerosis-Associated Low CD4 and CD8 Levels

https://www.karger.com/Article/Pdf/448704

We  report  a  35-year-old  healthy  male  who  developed  central  nervous  system  inflammatory demyelinating  disease [ CNS IDD]  consistent  with  tumefactive  multiple  sclerosis.  About  2  weeks  after onset  of  symptoms  and  prior  to  initiation  of  therapy,  the  patient  had  lymphopenia  and  low CD4 and CD8 levels. His lymphocyte count was 400 cells/μl (850–3,900 cells/μl), CD4 was 193 cells/μl (490–1,740 cells/μl) and CD8 was 103 cells/μl (180–1,170 cells/μl). He was treated with intravenous methylprednisolone followed by therapeutic plasma exchange, the levels of CD4 and CD8 normalized, and ultimately, he recovered completely.
******
A unique aspect of our investigation  of  this  patient  are  the  immunological  parameters tested  in  the  patient  upon  initial  presentation  and  not  on  any  treatment.  His  CD4  and  CD8 counts were low, and to our knowledge, this is the first time this laboratory abnormality has been  observed  in  a  patient  with  IDD.  There  have  been  studies  of  the  role  of  CD4  and  CD8 cells in MS, where the implications of low levels of both of these
cell types is not clear, although a low CD4 count has been described in a number of conditions such as HIV disease
and levels of CD8 cells are reduced in patients treated with dimethyl fumarate [10]. However, the combination of reduced values of both the CD4 and CD8 levels has not been reported in any disorder [9, 11]. In this patient, this abnormality could be due to a prior viral infection which may have initiated the process of CNS demyelination. Alternatively, it  may represent the response of the immune system to the beginning of the disease process.
Whether abnormally low CD4 and CD8 levels are involved in the pathophysiology of IDD will require further confirmation with studies investigating CD4 and CD8 parameters in patients  early  in  the  clinical  course  prior  to  initiation  of  any  therapy.  If  our  results  are  confirmed, levels of CD4 and CD8 could represent a biomarker for tumefactive CNS IDD. Regardless of the specific pathophysiology, therapeutic plasma exchange should be a consideration in atypical cases of IDD consistent with tumefactive MS.
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Re: Krooniset bakteeri-infektiot
Vastaus #303 - 07.01.2017 - 15:18:06
 
Autoimmunity and infections: When the body fights itself

https://www.sciencedaily.com/releases/2017/01/170106092354.htm

January 6, 2017
Basel-based doctors are on the trail of a possible connection between autoimmune diseases and infections: errors can occur when immune cells absorb certain proteins from pathogen cells. These findings were reported in the journal PNAS by researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel, as well as colleagues in the USA.

It is already known that there is a connection between infections and autoimmunity -- the inability of an organism to recognize parts of its own body as "self." As a result, increasing hygiene is leading to a higher incidence of autoimmune diseases in the population. It is also apparent that some autoimmune diseases are triggered by infections. However, the mechanism behind these connections is still not fully understood. One possible explanation is that the immune system confuses protein structures from pathogens with the body's own proteins because they look structurally alike.

Errors in protein uptake

Together with colleagues from the Whitehead Institute in Cambridge (USA), the Basel-based team of researchers tested out a new hypothesis in experiments to investigate the special ability of immune cells to identify specific proteins on the surface of neighboring cells and capture them from the cell membrane. In certain cases, errors can occur in the uptake of these proteins, as the group led by Professor Tobias Derfuss has now demonstrated.

Their assumption is that certain immune cells, so-called B cells, capture not only the protein of an influenza virus for which they were specialized but also small quantities of other neighboring membrane proteins. One example of this is a protein known as an autoantigen that originates from the cell membrane layer in the central nervous system. An immune response to this membrane protein results in an autoimmune inflammation in the brain in the animal model and may well also contribute to inflammation of this kind in humans.

Harmful immune cells

B cells cultivated with cells that had incorporated both the influenza virus protein and the membrane protein were not only able to activate other immune cells, specifically certain T cells, in order to combat the virus; they also activated T cells that had recognized the body's own membrane protein -- which can trigger autoimmune inflammation in the brain. Consequently, a viral infection could lead to the activation of autoaggressive T cells through an error in the protein uptake of B cells.

The researchers discovered this mechanism after conducting experiments using cells from genetically modified mice. "The next step would now be to examine whether similar errors occur in protein uptake by human B cells. We also want to clarify whether a viral infection in an animal can, under certain circumstances, lead to autoimmune inflammation in the brain," says Derfuss. Corresponding follow-up projects are planned.
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Re: Krooniset bakteeri-infektiot
Vastaus #304 - 07.01.2017 - 15:25:24
 
Factors responsible for chronic nature of autoimmune disease identified

https://www.sciencedaily.com/releases/2017/01/170104114327.htm

January 4, 2017
Researchers from Schepens Eye Research Institute of Massachusetts Eye and Ear have uncovered two factors responsible for the chronic, lifelong nature of autoimmune disorders, which tend to "flare up" intermittently in affected patients. These two factors are cell-signaling proteins called cytokines -- specifically Interleukin-7 and -15 (IL-7 and IL-15) -- that are secreted by cells of the immune system and help modulate memory Th17 cells, a subset of T cells which are known to contribute to autoimmune disorders. Until now, it was unclear how Th17 cells maintained memory; the study results show that IL-7 and IL-15 signal the Th17 cells to chronically reside in the body. These findings, published online in the Journal of Autoimmunity, may lead to the development of new therapies to address a variety of chronic autoimmune disorders.

"We wanted to know the precise factors that maintain memory in Th17 cells so that we can better understand what is causing chronic autoimmune disorders," said senior author Reza Dana, M.D., M.Sc., MPH, Director of the Cornea and Refractive Surgery Service at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. "By selectively targeting the production and expression of IL-7 and IL-15, we may be able to prevent the development of chronic autoimmune disorders."

Affecting up to 50 million Americans, autoimmune disorders develop when the body's immune system attacks its own healthy tissue. Many autoimmune disorders are chronic, and patients may experience "flare-ups," in which symptoms worsen temporarily and then enter a period of remission.

Previous research studies have linked Th17 cells to a variety of autoimmune disorders, including multiple sclerosis,
rheumatoid arthritis, inflammatory bowel disease, and chronic inflammatory eye disorders such as uveitis and dry eye disease. When Th17 cells are activated, a subset of them become memory cells, causing them to reside in the body for long periods of time. These memory Th17 cells can become reactivated and cause flare-ups of the autoimmune condition. However, the underlying mechanisms that promote the maintenance of Th17 memory were previously unknown.

Using a mouse model for dry eye disease, an autoimmune condition affecting the surface of the eye, the study authors set out to determine what molecular factors are critical for the maintenance of Th17 memory. They identified IL-7 and -15 as playing a crucial role in the survival and homeostatic proliferation of memory Th17 cells, and when they neutralized IL-7 and IL-15, they saw a substantial reduction of memory Th17 cells.

While further studies are needed to determine ways to block these factors, the findings suggest that targeting IL-7 and IL-15 in order to remove the memory Th17 cells may be an effective treatment strategy for autoimmune diseases.

"In the case of dry eye disease, many of the treatments are showing limited efficacy in patients that do not have a highly inflamed eye," said Dr. Dana. "Targeting the chronic, immune nature of autoimmune diseases may be a better strategy for controlling these conditions."

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Re: Krooniset bakteeri-infektiot
Vastaus #305 - 29.01.2017 - 14:59:18
 
Defective T-cell control of Epstein–Barr virus infection in multiple sclerosis

http://www.nature.com/cti/journal/v6/n1/full/cti201687a.html

20 January 2017
Mounting evidence indicates that infection with Epstein–Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8+ T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects. In 20 HLA-A2+ healthy subjects and 20 HLA-A2+ patients we also analysed CD8+ T cells specific for individual peptides, measured by binding to HLA-peptide complexes and production of IFN-γ, TNF-α and IL-2. We found a decreased CD8+ T-cell response to EBV lytic, but not CMV lytic, antigens at the onset of MS and at all subsequent disease stages. CD8+ T cells directed against EBV latent antigens were increased but had reduced cytokine polyfunctionality indicating T-cell exhaustion. During attacks the EBV-specific CD4+ and CD8+ T-cell populations expanded, with increased functionality of latent-specific CD8+ T cells. With increasing disease duration, EBV-specific CD4+ and CD8+ T cells progressively declined, consistent with T-cell exhaustion. The anti-EBNA1 IgG titre correlated inversely with the EBV-specific CD8+ T-cell frequency. We postulate that defective CD8+ T-cell control of EBV reactivation leads to an expanded population of latently infected cells, including autoreactive B cells.
***********
In this comprehensive study of the T-cell response to EBV in MS, we have shown that there is a decreased CD8+ T-cell response to EBV lytic phase antigens at the onset of MS and at all subsequent stages of the disease. In contrast to the decreased response to the lytic antigens of EBV, the CD8+ T-cell response to the lytic antigens of CMV, another common human herpesvirus, was normal in patients with MS. Even in healthy EBV carriers, EBV is continuously being reactivated in the tonsil with shedding of virions into saliva,5 a process normally kept in check by lytic-specific cytotoxic CD8+ T cells (Figure 7a).7, 8 Thus the predicted consequence of defective CD8+ T-cell control of EBV reactivation is increased production of infectious virions with increased oral shedding, as occurs in children with MS,37 and increased infection of new naive B cells, which become blasts in a new cycle of infection (Figures 7b and d).6 Indeed the amplification of virus production in the tonsil wherein virus released from each bursting plasma cell infects epithelial cells which in turn generate enough virions to infect ~10 000 naive B cells6 means that impaired immune control of this critical stage of the EBV life cycle can have a major follow-on effect into the infected blast population. The crucial importance of controlling the lytic phase of infection is also supported by the study of Hopwood et al.38 who concluded that in healthy individuals viral loads are maintained within normal limits by cytotoxic CD8+ T cells directed against lytic rather than latent EBV proteins. According to the mathematical model of EBV infection proposed by Hawkins et al.,6 increased input into the EBV-infected blast pool from the lytic phase will increase the size of the blast population, in turn stimulating the expansion of CD8+ T cells specific for EBV latent antigens, as we found in patients with MS. If the increase in latent-specific cytotoxic CD8+ T cells suffices to counteract the increased input into the blast population, the size of the infected blast cell population remains at its pre-existing healthy size at the expense of a sustained increase in the latent-specific CD8+ T-cell population. However, if the persistently high EBV latent antigen load induces T-cell exhaustion of the latent-specific T cells, as occurs in high-grade chronic viral infections, the increased input into the blast pool from the lytic phase is no longer counterbalanced by the T-cell response, so that the blast population increases in size, as does its input into the germinal centre pool. We have shown that there is indeed T-cell exhaustion of CD8+ T cells recognizing EBV latent antigens in MS. Interestingly the T-cell exhaustion appears preferentially to affect CD8+ T cells responding to the EBNA3C-derived LLD peptide rather than the LMP2A-derived CLG and FLY peptides. Potential explanations for the predilection of EBNA3C-specific CD8+ T cells to exhaustion include their immunodominance and the earlier expression of EBNA3 proteins than LMP proteins after infection of naive B cells. Increased input of cells from the expanded EBV-infected blast pool into the germinal centre pool will enlarge the infected germinal centre B-cell population, which will continue to grow if inadequately controlled. Furthermore, unchecked growth of the EBV-infected germinal centre B-cell pool will increase the infected memory B-cell population and thus the number of latently infected cells available to reactivate the virus into the lytic stage, thereby further taxing the already impaired EBV-lytic-specific CD8+ T-cell response. This in turn leads to increased generation of virions which infect naive B cells, driving them into clonal expansion with further enlargement of the EBV-infected blast population—truly a vicious cycle. Progressive exhaustion of EBV-latent-specific T cells will permit unbridled proliferation of EBV-infected germinal centre B cells (Figure 7d), which might underlie the development of EBV-infected lymphoid follicles in the brain in secondary progressive MS.
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Re: Krooniset bakteeri-infektiot
Vastaus #306 - 15.02.2017 - 21:42:46
 
IL-17 increases in secondary progressive MS

http://multiple-sclerosis-research.blogspot.com/2014/09/il-7-increases-in-second...


Sunday, 28 September 2014

OBJECTIVE:In the current exploratory study, we longitudinally measured immune parameters in the blood of individuals with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and investigated their relationship to disease duration and clinical and radiologic measures of CNS injury.
******
RESULTS: Frequencies of myelin basic protein-specific IL-17- and IFN-γ-producing PBMCs were higher in individuals with RRMS and SPMS compared to healthy controls. Patients with SPMS expressed elevated levels of IL-17-inducible chemokines that activate and recruit myeloid cells. In the cohort of patients with SPMS without inflammatory activity, upregulation of myeloid-related factors correlated directly with MRI T2 lesion burden and inversely with brain parenchymal tissue volume.
CONCLUSIONS: The results of this exploratory study raise the possibility that Th17 responses and IL-17-inducible myeloid factors are elevated during SPMS compared with RRMS, and correlate with lesion burden. Our data endorse further investigation of Th17- and myeloid-related factors as candidate therapeutic targets in SPMS.
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Re: Krooniset bakteeri-infektiot
Vastaus #307 - 15.02.2017 - 21:54:26
 
The Antibody Response to Epstein-Barr Virus in Multiple Sclerosis Is Increased Only to Selected Antigens

http://www.neurology.org/content/86/16_Supplement/P5.344

Objective: The objective of this work was to identify Epstein-Barr virus (EBV) proteins that are the targets of an increased antibody response in multiple sclerosis (MS).
Background: EBV is associated with MS. One of the most consistent findings has been that antibodies to the EBV nuclear antigen-1 [b](EBNA-1) are increased in MS[/b]. Only a limited number of other EBV proteins have been investigated. Our previous work using Western blots demonstrated that most people have antibodies to many different EBV proteins, and suggested that antibodies were increased to some, but not all, EBV antigens in MS patients.
Methods: We immunoprecipitated EBV proteins using either MS or control IgG, and identified the bound proteins using iTRAQ quantitative mass spectrometry. We compared the amounts bound by MS or control IgG. We then selected and produced single EBV proteins, and used quantitative immunoassays to compare the antibody response in 80 MS patients and 80 matched controls.
Results: Mass spectrometry identified 28 EBV proteins that were immunoprecipitated by MS or control IgG. Fifteen of these proteins were more concentrated in the MS immunoprecipitate. We selected 8 individual EBV proteins for further study. The antibody response to EBNA-1 was significantly increased in MS (p<0.001), as was the antibody response to the small capsid protein BFRF3 (p=0.007) and the tegument protein BRRF2 (p=0.006). The antibody response to the other 5 antigens was not increased in MS.
Conclusions: The anti-EBV antibody response is increased only to selected EBV antigens in MS patients. This finding may be relevant to the pathogenesis of MS.

*******
Ts, jos EBV testataan, niin täytyy vaatia, että tutkitaan EBNA-1. Itselläni sitä ei ole Suomessa mitattu, kun taas Saksassa se  oli >600 (normaali <5).
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Re: Krooniset bakteeri-infektiot
Vastaus #308 - 15.02.2017 - 22:01:08
 
The Interplay Between Epstein Barr Virus and B Lymphocytes: Implications for Infection, Immunity, and Disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199828/

Human B cells are the primary targets of Epstein Barr virus (EBV) infection. In most cases EBV infection is asymptomatic because of a highly effective host immune response but some individuals develop self-limiting infectious mononucleosis, while others develop EBV-associated lymphoid or epithelial malignancies. The viral and immune factors that determine the outcome of infection are not understood. The EBV life cycle includes a lytic phase, culminating in the production of new viral particles, and a latent phase, during which the virus remains largely silent for the lifetime of the host in memory B cells. Thus, in healthy individuals there is a tightly orchestrated interplay between EBV and the host that allows the virus to persist. To promote viral persistence EBV has evolved a variety of strategies to modulate the host immune response including inhibition of immune cell function, blunting of apoptotic pathways, and interfering with antigen processing and presentation pathways. In this article we focus on mechanisms by which dysregulation of the host B cell, and immune modulation, by the virus can contribute to development of EBV+ B cell lymphomas.
*********
In conclusion, EBV infection initiates a complex, ongoing interplay between the virus, the host B cell and the immune response. EBV has successfully employed a variety of strategies to promote viral persistence in healthy individuals, however, dysregulation of these pathways, or perturbation of host immunity, may contribute to the development of EBV-associated malignancies. Future studies to elucidate the mechanisms by which EBV coopts B cell function, the immune response to EBV, and the significance of viral diversity will be important in understanding the outcome of EBV disease.
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Re: Krooniset bakteeri-infektiot
Vastaus #309 - 15.02.2017 - 22:10:41
 
Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis

http://www.direct-ms.org/pdf/InfectiousMS/Cepak%20EBV%20in%20MS.pdf

MS is a chronic inflammatory and demyelinating disease of the CNS with as yet unknown etiology. A hallmark
of this disease is the occurrence of oligoclonal IgG antibodies in the cerebrospinal fluid (CSF). To assess the
specificity of these antibodies, we screened protein expression arrays containing 37,000 tagged proteins. The 2
most frequent MS-specific reactivities were further mapped to identify the underlying high-affinity epitopes.
In both cases, we identified peptide sequences derived from EBV proteins expressed in latently infected cells.
Immunoreactivities to these EBV proteins, BRRF2 and EBNA-1, were significantly higher in the serum and
CSF of MS patients than in those of control donors. Oligoclonal CSF IgG from MS patients specifically bound
both EBV proteins.
Also, CD8+ T cell responses to latent EBV proteins were higher in MS patients than in controls. In summary, these findings demonstrate an increased immune response to EBV in MS patients, which
suggests that the virus plays an important role in the pathogenesis of disease
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Re: Krooniset bakteeri-infektiot
Vastaus #310 - 17.03.2017 - 17:57:42
 
CONTROVERSIES  IN  LATE  NEUROBORRELIOSIS  AND  MULTIPLE  SCLEROSIS  
CASE  SERIES

http://www.mms-seminar.com/wp-content/uploads/2015/08/2009-romanian-study-ms-is-...

2009
Abstract.
Introduction
The  etiology  of  MS  remains  uncertain,  bacterial  infection  with  B.  burgdorferi  is  most  frequently  incriminated.  Neuroimaging  criteria  considered  in  the  diagnosis  of  MS  can  also  be fulfilled  in  NB,  the  joint  feature  being  demyelinating  lesions.  We  present  the  diagnosis  and  treatment difficulties  in  NB  versus  MS  and  other  clinical  considerations.

Methods
We  retrospectively  studied  all  consecutive  cases  of  neuroborreliosis  hospitalized  in  the  University  Hospital  of  Infectious  Diseases  during  2006-2008.  The  diagnosis  was  established  through  clinical  criteria  (using  a  probability  score  for  Lyme  disease),  serological  criteria  (enzyme  immunoassay  for  IgM  and IgG antibodies followed by confirmatory Western blot) and MS diagnosis was stratified as confirmed or  possible  according  to  MacDonald’s  criteria.

Results
There were 36 cases of probable or highly probable neuroborreliosis (score ≥6), out of which ten cases  were  also  diagnosed  as  possible  (5)  or  confirmed  MS  (5).  The  age  range  was  19  to  43  years,  with  female  predominance  (7/10).  The  clinical  picture  was  marked  by  poor  stamina  and  fatigue,  paresthesia  mainly  in  the  lower  extremities,  palsies  (facial  or  in  the  limbs),  difficult  walking  and  vertigo.  In  all  cases  the  screening  enzyme  immunoassay  was  positive  for  IgM  antibodies,  confirmatory  Western  blots  were  positive  in  four  out  of  seven  tests  performed.  Tick  exposure  was  identified  in  5  cases  without  erythema  migrans.  In  all  patients  cerebral  imaging  examination  revealed  demyelinating  lesions  that  were  interpreted  as  late  NB  and/or  MS  (possible  or  confirmed).  Treatment  with  neurotropic  drugs  and  antibiotics  was  done  and  the  five  patients  with  confirmed  MS  received  beta  interferon  or  corticosteroids.  All  cases  demonstrated  improvement  after  6  weeks  of  sequential  treatment  (ceftriaxone  and  doxycycline).  In  one  case,  the  diagnosis  of  cerebral  lymphoma  was  considered  suggesting  the  association  between  NB  and  MS  or  neuroborreliosis  mimicking  primary  effusion lymphoma.

Conclusions.
The  diagnosis  of  MS  and  NB  are  difficult  showing  remarkable  clinical  and  neuroimaging  similarities.  The  infectious  etiology  of  MS  remains  probable  and  in  patients  with  possible  MS  it  is  reasonable  to  evaluate  B.  burgdorferi  infection  in  order  to  ensure  etiologic  treatment.
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Re: Krooniset bakteeri-infektiot
Vastaus #311 - 07.04.2017 - 17:43:55
 
Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal

http://www.jni-journal.com/article/S0165-5728(17)30055-3/abstract?cc=y=

March 2017

Abstract

Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is a potentially life-threatening event. To verify whether highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during a fulminating MS relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation.
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Kaksi seikkaa tästä artikkelista: Tysabrin lopettaminen voi olla hengenvaarallista ja toiseksi sen teho näyttää perustuvan siihen, että se pitää EBV:n kurissa.
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Re: Krooniset bakteeri-infektiot
Vastaus #312 - 07.04.2017 - 17:59:00
 
Viimeisten testien mukaan minulla on aktiivinen EBV, yhä kaikkien vuosien jälkeen. Ja siihen liittyen CD8 arvo on normaalia pienempi, CD4 normaali, ja niiden suhde normaalia kaksinkertaisesti suurempi. CD8 T-solut tappavat solunsisäisiä bakteereita ja viruksia, ja niitähän minulla on riittänyt. Toisin sanoen immuunipuolustukseni on melko heikko. Mutta tulokset ovat aivan Penderin tutkimusten mukaisia. Sain teetettyä kokeet ulkomailla (Virossa), koska Suomessa en pääse neurologin vastaanotolle edes keskustelemaan.
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Re: Krooniset bakteeri-infektiot
Vastaus #313 - 07.04.2017 - 19:15:10
 
Defective T cell control of EBV in MS

http://multiple-sclerosis-research.blogspot.com/2017/03/

Clin Transl Immunology. 2017;6(1):e126

Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8+ T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects. In 20 HLA-A2+ healthy subjects and 20 HLA-A2+ patients we also analysed CD8+ T cells specific for individual peptides, measured by binding to HLA-peptide complexes and production of IFN-γ, TNF-α and IL-2. We found a decreased CD8+ T-cell response to EBV lytic, but not CMV lytic, antigens at the onset of MS and at all subsequent disease stages. CD8+ T cells directed against EBV latent antigens were increased but had reduced cytokine polyfunctionality indicating T-cell exhaustion. During attacks the EBV-specific CD4+ and CD8+ T-cell populations expanded, with increased functionality of latent-specific CD8+ T cells. With increasing disease duration, EBV-specific CD4+ and CD8+ T cells progressively declined, consistent with T-cell exhaustion. The anti-EBNA1 IgG titre correlated inversely with the EBV-specific CD8+ T-cell frequency. We postulate that defective CD8+ T-cell control of EBV reactivation leads to an expanded population of latently infected cells, including autoreactive B cells.
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So what did this study find

   The T-cell response to EBV-infected B cells is reduced at all stages of MS except during clinical attacks

   The T-cell response to EBV-infected B cells progressively decreases with increasing duration of MS.

These results are consistent with progressive T-cell exhaustion of EBV-specific CD4+ T cells and CD8+ T cells during the course of MS although they could also be due to other factors, for example an age-related decline in the tendency of EBV to reactivate.

T cell exhaustion is a state of T cell dysfunction that arises during many chronic infections and cancer. It is defined by poor effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells.

The CD8+ T-cell response to EBV lytic phase antigens is reduced at the onset of MS and throughout its course.
CD8+ T cells recognizing EBV latent phase antigens in MS show T-cell exhaustion.

To test this model they suggest that further studies are necessary to determine:
(i) the cause of CD8+ EM/EMRA T-cell deficiency in MS, whether it genetically determined, and related to decreased type I IFN production;
(ii) whether CD8+ T-cell deficiency precedes the onset of MS and is present in healthy first-degree relatives of people with MS,
(iii) whether sunlight deprivation and vitamin D deficiency aggravate the CD8+ T-cell deficiency
(iv) how and why the EBV-specific CD4+ T-cell response declines during the course of MS;
(v) whether oral shedding of EBV is increased during clinical attacks;
(vi) whether the frequency of EBV-infected memory B cells in the blood is increased in MS, as in rheumatoid arthritis and systemic lupus erythematosus;
(vii) whether EBV-infected B cells and plasma cells in the CNS in MS are autoreactive, and (viii) finally and most importantly, whether therapies aimed at controlling EBV infection, such as EBV-specific T-cell therapy,prevent and cure MS.
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Re: Krooniset bakteeri-infektiot
Vastaus #314 - 21.04.2017 - 16:05:18
 
Preliminary study suggests possible new treatment for MS

https://www.sciencedaily.com/releases/2017/04/170420162236.htm

A small, preliminary study may show promise of a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase 1 study, a study designed to enroll 10 people, are being presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017.

Phase 1 studies are designed to evaluate the safety of a treatment and identify side effects, using a small number of participants. While it was not the goal of this study to measure how effective the treatment was, symptoms improved for three of the six participants.

"While these results are very preliminary and much more research is needed, we are excited there were no serious side effects," said study author Michael Pender, MD, PhD, of The University of Queensland in Brisbane, Australia.

The study investigates the relationship between MS and the Epstein-Barr virus (EBV), a herpes virus that is extremely common but causes no symptoms in most people. However, when a person contracts the virus as a teenager or adult, it often leads to mononucleosis. Previous research has shown a link between the virus and MS.

The study involved six people with progressive MS with moderate to severe disability. People with progressive MS have a severe condition with slow, steady worsening of symptoms.

In MS, the body's immune system attacks the nerves in the central nervous system. As part of the normal immune response, immune cells called T cells and B cells work together to protect the body against infectious agents. In some people with MS, the immune response may be altered and T cells may be unable to control EBV-infected B cells, which accumulate in the brain and produce antibodies that attack and destroy myelin, the protective layer that insulates nerves in the brain and spinal cord. This in turns leads to neurologic dysfunction and symptoms. Elimination of the EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with Epstein-Barr virus. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients through 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three of the participants showed improvement, starting two to eight weeks after the first infusion.

"One person with secondary progressive MS showed striking improvement," Pender said. "This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one sided assistance. Lower leg spasms that had persisted for 20 years resolved."

Pender said another participant with primary progressive MS showed improved color vision and visual acuity.

All three responding participants had improvements in fatigue and ability to perform daily activities.

"The best responses were seen in the two people who received T cells with the highest amount of reactivity to the Epstein-Barr virus," Pender said.

None of the six participants had serious side effects.

"Of course, much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings," Pender said. "But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.

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