Lactoferrin may protect B cells from ebv infection

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Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Fri Feb 14, 2014 6:52 am

http://www.ncbi.nlm.nih.gov/m/pubmed/22433582/
Lactoferrin (LF) is a multifunctional glycoprotein that plays an important role in native immune defense against infections, including human herpetic viruses, such as cytomegalovirus and herpes simplex virus types 1 and 2. However, its anti-Epstein-Barr virus (EBV, a γ-herpesvirus) function has not been reported in the literature. EBV is widespread in all human populations and is believed to be linked to tumorigenesis, such as lymphomas and nasopharyngeal carcinoma (NPC). We previously reported that LF expressed a significantly lower level in NPC tissues and was a likely tumor suppressor. Since EBV infection is a major carcinogen of NPC development, we investigated the effect of LF on EBV infection and found that LF could protect human primary B lymphocytes and nasopharyngeal epithelial cells from EBV infection, but had no effect on EBV genome DNA replication. LF prevented EBV infection of primary B cells mediated by its direct binding to the EBV receptor (CD21) on the B-cell surface. Tissue array immunohistochemistry revealed that LF expression was significantly downregulated in NPC specimens, in which high EBV viral capsid antigen-IgA levels were observed. These data suggest that LF may inhibit EBV infection and that its downregulation could contribute to NPC development.

Copyright © 2012 S. Karger AG, Basel.

Available at health food stores in the immune boosting section. I started taking it last night for a different reason but was pleased to find this paper this am. I might have to keep taking it to protect my new B cells. :D Will post if I react poorly to it.
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Re: Lactoferrin may protect B cells from ebv infection

Postby Leonard » Fri Feb 14, 2014 6:58 am

yes please let us know, also if you react well, but I gues it will take some time, possibly half a year or more.
it might be useful to get your EBV viral load tested at several time intervals to see what happens.
very interested in this, wow... thanks
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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Fri Feb 14, 2014 7:36 am

Hi Leonard,

I'm in a bit of a different spot than most at the moment. I had 4 weekly rounds of iv and it rituxan in October so most of my B cells have been killed off (plasma cells still there)...few ebv infected left. I'm also having iron/ferritin issues so my reaction to the lactoferrin (which handles iron in various ways) may not be typical. You might be best off giving it a try yourself.

You might find more natural ways of fighting ebv by researching ptld, burkitts lymphoma, and nasopharyngeal cancers.
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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Fri Feb 14, 2014 10:12 am

Full text for study
http://www.karger.com/Article/FullText/336178

Also, this wouldn't be enough to fully address ebv issue. Aside from lactoferrins inability to prevent ebv replication, ebv also binds to another B cell receptor, cd35. Maybe lactoferrin binds that site as well but it wasn't documented initial study.
Ebv and cd35
http://www.ncbi.nlm.nih.gov/m/pubmed/23416052/
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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Fri Feb 14, 2014 12:16 pm

That's a great piece of work. Intuitively, it looks like you should take this. Particularly post Rituxan.
They make it very clear it only works on primary B cells and epithelial cells but that's what you need right now.
I'll see if I can find some and see how I react to it.

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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Fri Feb 14, 2014 4:15 pm

This is a good article too.

http://www.nature.com/ki/journal/v57/n5 ... 91533a.pdf

"In summary, our results show that the kidney produces LF in a highly ordered fashion and that only a minor fraction of this LF is secreted into the urine. These findings indicate that LF has important functions in both the immune defense of the urinary tract and in the general metabolism. It is also possible that LF has an important role in the antioxidant defense systems."

Lactoferrin is critical to the ordered role of iron. In turn this plays a part in the control of infection and inflammation.

This really deserves a bit of our time.

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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Fri Feb 14, 2014 5:09 pm

Okay. Some more time gave me this...yikes.
http://www.ncbi.nlm.nih.gov/pmc/article ... rt=classic
In contrast, orally administered lactoferrin given to multiple sclerosis patients, naive mice, or tumor-carrying mice increased IFN-γ levels [157,158,164], indicating an increase in TH1 T-cell response. Similarly, Staphylococcus aureus infection of transgenic mice expressing human lactoferrin saw a shift of host responses towards TH1, as observed by increased levels of IFN-γ and TNF-α and decreased IL-5 and IL-10 [165]. This polarization of host immunity towards TH1 by lactoferrin can remain even after the initial T-cell activation subsided. In one specific example of polarization, recall responses in mice vaccinated with BCG/lactoferrin exhibited higher production of IFN-γ compared to mice immunized with BCG only [166,167]. The ability of lactoferrin to modulate antigen-specific T-cell response that can last several weeks after the initial sensitization suggest that lactoferrin affects events during priming of naïve T-cells to specific antigens.
B lymphocytes
In addition to lactoferrin’s role as a modulator of excessive response, an eloquent series of experiments demonstrated that lactoferrin can also function to enhance depleted immunoreactivity. This is most evident in the role of lactoferrin to affect B lymphocytes. Lactoferrin has the ability to promote maturation of murine immature B-cells, evident by increasing complement 3 receptor (C3R) expression and promoting acquisition of surface IgD. Immature B-cells cultured with lactoferrin increased their ability to promote antigen-specific T-cell proliferation, indirectly indicating enhanced B-cell antigen presentation [48]. B-cell presented antigens specifically stimulated T-cells to induce cytokines required for isotype switching events. Oral delivery of lactoferrin increased secretion of overall IgA and IgG from murine Peyer’s patches [168] with specific antibody titers remaining elevated in both serum and intestinal secretions [159]. In a chemotherapy-induced immune suppression murine model, lactoferrin given intraperitoneally prior to a sub-lethal dose of cyclophosphamide lessened the suppression of antibody forming cells. Lactoferrin was also able to facilitate restoration of the immune response [156]. In another series of experiments, lactoferrin specifically exhibited the ability to overcome the suppressive action of methotrexate in the secondary, humoral immune response to sheep erythrocytes in mice [169]. Furthermore, the biological activity of different glycoforms was tested in vitro, revealing the importance of N-acetylneuraminic (sialic) acid as a terminal sugar in propagation of the reconstituted immune responses [170]. Consequentially, this suggests that lactoferrin can act on B cells, a known antigen presenter, to allow subsequent T cells interactions that favor elevation of the antibody response.

You'd really have to buy into the ebv/ms theory to take it...

I'm not stopping yet but that's because I probably have fewer antigen presenting cells for now.
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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Fri Feb 14, 2014 6:14 pm

About that ifn-y increase. It was tried in a group of 18 (I think) msers for 4 weeks only. They all relapsed. Oops! Edit: only 7/18 relapsed. http://m.neurology.org/content/37/7/1097.short So ifn-y is known to be an ms bad guy. But...in light of Penders recent case study, what do you think about that and this....??
http://m.cid.oxfordjournals.org/content ... pdf#page=1 (full study)
A 26-year-old previously healthy woman developed granulomatous pneumonitis, encephalitis, and genital ulceration during primary Epstein-Barr virus (EBV) infection. EBV DNA was demonstrated by polymerase chain reaction analysis of serum, lung tissue, and genital ulcer specimens. Serology verified primary EBV infection. The patient lacked lymphocytes cytotoxic to autologous EBV-transformed B lymphocytes. No spontaneous or in vitro EBV-induced interferon gamma (IFN-gamma) production was evident in peripheral blood. The cells had normal IFN-gamma production when stimulated with Staphylococcus aureus exotoxin A. In the bone marrow and peripheral blood, the number of large granular CD56+ lymphocytes (natural killer cells) increased 39%-55%, but no CD4 or CD8 cell lymphocytosis was initially found. A partial clinical response was achieved with treatment with acyclovir, corticosteroids, and intravenous gamma-globulin. Because of persistent granulomatous central nervous system and lung involvement, subcutaneous IFN-gamma therapy was started but was discontinued after 3 months because of development of fever, pancytopenia, and hepatitis. This therapy initiated a complete clinical recovery, which occurred parallel to development of EBV-specific cytotoxic CD8+ T lymphocytes and normalization of natural killer cell lymphocytosis. These findings provide evidence for an EBV-induced lymphoproliferative disorder due to a T lymphocyte dysfunction associated with a selective lack of IFN-gamma synthesis.
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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Sat Feb 15, 2014 2:47 am

The conclusion I'm forced to draw based on that last link is IFN-y will flare as a result of an increase in viral particles as the virus enters a lytic phase. All interferons are antiviral so they should signal NK cells as particles increase. If Lactoferrin prevents EBV from binding then I guess the immune system thinks more are in circulation. I recall EBV uses phox 47 to help it hide from the immune system. Perhaps (I don't know) the Lactoferrin by blocking the binding to a B cell exposes the EBV by interfering with the action of phox 47 exposing the virus to the immune system and promoting a IFN-y response. It may be a case of just using Valacyclovir to limit the EBV in lysis and looking through the IFN-y surge.

Interesting isn't it!
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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Sat Feb 15, 2014 8:06 am

Definitely interesting. I noticed in the ifn-y study that csf igg numbers didn't change...which should have happened at some point if ebv were the cause of increased igg and was the target of relapse. Maybe they tested before the antibodies could clear out of csf.

I've started to get the weird head I get with supplementing iron these days so have to give up on the lactoferrin (and iron) for now. To be clear, I don't feel like my ms is worse...I feel the stupid iron in my brain. Grrr.

If you try lactoferrin, post your reaction. :) I might try again once I'm straightened out.
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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Sat Feb 15, 2014 11:53 am

What I'm hoping is I don't notice a reaction!

I thought about this all night and I ended up casting my mind back to when I started taking the combination of Avonex and Valtrex. At that stage Avonex wasn't doing much for me and I had significant problems with brain fog and the body wasn't that flash either. When I added the Valtrex there was a noticeable improvement. If I tried one without the other I could only go five weeks without a noticeable deterioration.
If I use that time as an analogue for what I'm about to try, the thinking will be along these lines- The Avonex was a signaling agent to wake up the immune system and, of itself, was not antiviral. That's all interferon does anyway. The Valtrex was the antiviral and inserted a stop in the codan of the EBV RNA. As the interferon had woken up the immune response, the EBV, weakened by Valtrex, was more susceptible to body's natural defenses.
This time round, the lactoferrin may be affecting the shell of the EBV making it visible to the immune system (perhaps by knocking out phox 47) so the normal reaction is the body increases interferon production as a response (IFN-y) without stimulation. The immune system makes a better attempt at clearing circulating EBV because it is unbound. We can boost this response by adding Valacyclovir (Valtrex) to weaken the virus.
Timing might be critical. The study you published shows IFN-y was discontinued after a time but the end result was a cure for the girl. As they were inducing the IFN-y and it wasn't a natural response it muddies the picture a little. I also recall that a single Valtrex tablet's usefulness is completely depleted after 17hours. That's why I took one morning and night.
I will have to make a giant leap here; I will assume the lactoferrin definitely stops EBV binding to a primary B cell so it becomes vulnerable to discovery by the immune system and the potent life of this action lasts some time. Also I will assume that my immune system is functioning just fine because of all the things I already do.
So for me, I will start on day 1 taking a Valtrex morning and night and on day 2 start taking lactoferrin for 7 days. After that I will stop the lactoferrin for a week but keep the Valtrex going at a half dose (because I'm actually quite well). Then I will repeat it again. If I last the course I will report back then. If I fall over I will report sooner. This is all subject to sourcing the lactoferrin.

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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Sun Feb 16, 2014 7:40 am

Sounds like a plan. :) If you can't find lactoferrin, I believe it will probably be in colostrum supplements. Maybe it would be better to get the full benefit of colostrum anyway? There's some pretty sketchy info out there on colostrum and ms though.

I quickly returned to normal head and started taking a new iron supplement (has liver in it. Gross!). So far so good. I should be able to try the lactoferrin again in a week or so if everything stays good with the new iron supplement.

I'm interested to see how it goes for you. It seems like based in your avonex/valtrex notes, herxing shouldn't be an issue. So for those with higher ebv loads than we currently have, if they feel worse taking lactoferrin, it's aggravation of ms, no? Probably too many assumptions being made to say that.

Good luck!
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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Sun Feb 16, 2014 11:04 am

I don't think we could say. It would be a very poorly constructed argument to blame a herx on EBV if you haven't tested for other infections first. There is a long list of other things that could be the cause of an adverse reaction. There a very great need to avoid putting people into neat little boxes yet that's what happens. Some doctors act though the approach is "oh, now we know you have MS we should blame everything on that"!

Hopefully I just sail through this. I have the lactoferrin on order.

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Re: Lactoferrin may protect B cells from ebv infection

Postby Scott1 » Mon Feb 17, 2014 3:54 am

This is trickier than it looks!

I've started the Valtrex to give me cover but that's the easy part. The Lactoferrin I've got is 150mg of bovine plus 150mg of Saccharomyces cerevisiae(boulardi) but it also has 1725iu per tablet of Retinyl palminate. The suggested dose is up to 5 tablets per day. I can't get the stuff straight.

If I take 5 tablets then its 750mg Lactoferrin plus 8625 iu of Vitamin A. I like my retinoids from Carrot juice. Not this way. So I will definitely be pulsing it. The yeast looks like it acts as a transport agent but its not going to be the same product as the links you posted had.

I'll give it a go but I'm now unsure how this will go.

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Re: Lactoferrin may protect B cells from ebv infection

Postby Anonymoose » Mon Feb 17, 2014 7:11 am

You can't get symbiotics brand? That's what I have and it's just lactoferrin (250mg once a day). I hate it when they throw a bunch of extras into supplements. It's *hard* to find anything decent without herbs and probiotics added these days. :(

I think it's a good idea to pulse it anyway (wouldn't have thought of it myself). It's a naturally produced by your body so I think taking it all the time, long term, might mess with the natural metabolism.
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