In this interview I discuss the connection between Epstein-Barr Virus and Autoimmune Disease
You can listen to the interview above or read the transcript below:
Dr. Brady: Dr. Hedberg lectures all over the place, a lot of integrative medicine conferences. He's published in many journals. He teaches advanced functional medicine courses with Functional Medicine Town, professional co-op and as adjunct faculty with Hawthorn University. Dr. Hedberg has found that many chronic diseases are a result of stealth infections and that's what we're going to focus on tonight. Basically, he's also formed a website and a community known as "The Infection Connection" and I'll have him tell you a little bit more about that later in the call. You can learn more at infectionconnection.net.
Nick's a good friend of mine. I've known him for probably, I don't know, over 10 years I would say. He has the perfect radio DJ voice, as I always say, and you'll hear in a minute. When you hear that voice, I didn't know this at first, I learned this only in few years ago, but it did not surprise me when I found out that he's quite an accomplished opera singer. Nick, do you want to do a little tune for us to lead off or not?
Dr. Hedberg: No singing tonight Dave, LOL.
Dr. Brady: Okay. All right.
Dr. Hedberg: Yeah. Yeah.
Dr. Brady: All right. Well, thanks for being on, Nick, I appreciate it.
Dr. Hedberg: Yeah. It's great to be on again.
Dr. Brady: Great. Well, let's dive right into the topic. We're going to talk a lot about thyroid issues and stealth infections. We're going to look specifically tonight at the connections between Epstein-Barr virus and autoimmune diseases. I know that Epstein-Barr virus is certainly not the only virus out there implicated as an autoimmune potential trigger. Let's explore EBV first, so just give us an idea how you first started making the connection between EBV and autoimmune diseases, and just lay the groundwork for us, if you don't mind.
Dr. Hedberg: Right. So the first connection in the literature between EBV and autoimmune disease was actually in 1971. So a little over 40 years ago when they found that patients with Systemic lupus erythematosus had elevated antibody levels to EBV. It was actually about 10 years ago, David, you were talking about the connection between Yersinia and thyroiditis and that just kind of got me into looking at this molecular mimicry. So I just started noticing patterns on blood chemistry in patients with autoimmune diseases like low white blood cell counts, and then the class that has got elevated lymphocytes and low neutrophils which is the classic picture for a chronic viral activity. So I was seeing that a lot in the patients with autoimmune disease.
The other thing that shows up a lot in these patients were chronic low-grade fevers, getting fevers of unknown origin. A fever is basically an infection until proven otherwise. Then one of the other major red flag was, of course, cancer, but in these patients, cancer was not suspected. There was something going on there causing these chronic low-grade fevers. And then just started doing more and more Epstein-Barr virus panels on the autoimmune patients and seeing them coming back positive, reactivation of the Epstein-Barr virus. And then when I started focusing on that, the viral activity, that's when we started seeing excellent results in a lot of these patients.
Dr. Brady: I see. Did you happen to hear my interview earlier this year, in January sometime, with Derek Enlander, by any chance, from Columbia?
Dr. Hedberg: No. I didn't hear that.
Dr. Brady: Well, many of you on the call may have heard that. We talked about Myalgic Encephalomyelitis which is basically Fibromyalgia Chronic Fatigue Syndrome of viral origin. Of course, a lot of different viral agents are being studied and have been studied in relation to that, even though you wouldn't consider that necessarily an autoimmune disease classically. I think it's living in the same kind of sphere or camp and actually Enlander was first brought to the US by Stanford to study the relationship between Epstein-Barr virus and Cancer. So I thought it's kind of interesting. These calls kind of dovetail a little bit.
If you want to know more about his work, you can just look up Derek Enlander, you can go on our library and listen, download and listen to that Clinical Rounds call and some of the research he's doing at Columbia on Fibromyalgia Chronic Fatigue patients related to viral ideology and immune dysfunction from virus. But certainly this is in play in classic autoimmune conditions as well. So tell us just a little bit more about Epstein-Barr virus, some of the characteristics of the virus, the epidemiology of it out there, mechanisms, and can you share anything, anything meaty like that on EBV?
Dr. Hedberg: Right. So a lot of people forget that Epstein-Barr virus is a herpes virus. It's in that family. It's a gamma virus and it's very different from the other herpes virus in that it's the only one to infect B cells. It's these naive B cells that get infected. The other thing to know about it is that unlike, for example, say the flu virus where when the flu multiples and it expands, the cell is destroyed. There's almost instantaneous cellisis [SP] and viruses are spread into the system. The herpes viruses are very slow. What they do, it's called budding. The budding is just basically the virus is using the DNA to replicate itself, but the cell is actually not destroyed, and that's one of the main...
Dr. Brady: So that's why there's not such a virulent course or a [inaudible 00:13:57] obvious acute illness like there is with something like the flu, I would imagine.
Dr. Hedberg: Exactly. So it's slow like that and the host cell is spared by the virus. The other herpes viruses are of course, the cytomegalovirus virus and then we have herpes 1, 2, 6, 7 and 8. We're learning a lot more about herpes 6 and autoimmune disease, and then of course the varicella-zoster, chickenpox virus. About 95% of the world's population is infected with Epstein-Barr virus and most people get it before the age of three and they are asymptomatic.
Dr. Brady: What was the percentage you gave, Nick?
Dr. Hedberg: 95% percent.
Dr. Brady: Okay.
Dr. Hedberg: Yes. Most people will get it by the age of three, but there's no symptoms. And then, there's about 100% infection rate of those individuals, of course, by the time they reach adolescence. It's usually because they're stressed. The immune system is compromised or they get a higher viral load. Because EBV is the cause of the classic kissing disease, mononucleosis, and a lot of people will get that in adolescence, in high school and into college. So it is transmitted by saliva, and the first place that it infects is the B cells in the tonsils. That's where it germinates and that's where it really sets up shop.
Dr. Brady: If so many people, it's almost just universal that we're infected, what makes one person progress on to autoimmune disease or some other type of chronic illness and the majority of people not?
Dr. Hedberg: Right. That's what I'm talking about tonight, Dr. Pender's hypothesis of Epstein-Barr virus and autoimmunity. He has these eight-step hypothesis. Dr. Pender is out of the University of Queensland, School of Medicine in Australia. He breaks in down into eight steps. I just want to go through these briefly. Step one is a genetic CD8 T cell deficiency. So basically, these viral infected B cells are normally metabolized and controlled by cytotoxic CD8 T cells. If there's a genetic deficiency there, then it allows for an uncontrolled environment of the EBV infection. So you start with the genetic deficiency. The second part is of course the primary EBV infection.
Step three is a decreased cytotoxic CD8 T cells control of the infection. Step four is an increased EBV load and increased anti-EBV antibodies. Then step five is EBV infection in the target organ. So for example, these infected B cells with EBV actually would enter, for example, the thyroid gland and germinate in that area, and progress in maintaining a low-grade infection in the thyroid gland as an example. Other examples would be say the salivary glands and Sjogren's, the gut and Crohn's disease, examples like that. Step six is clonal expansion of the EBV-infected B cells in the target organ. Step seven, infiltration of autoreactive T cells into the target organ.
Finally, step eight, you get these ectopic lymphoid follicles in the target organ. So for example when you see a follicle on the thyroid, what they found is that that follicle was actually filled with EBV-infected B cells. So it's a really fascinating hypothesis that when you put it all together, it makes sense and it also would explain why if everyone has it, why doesn't everyone have autoimmune disease.
Dr. Brady: Can you pick up this genetic lack of those specific CD8 cells with lymphocyte subset testing or do you have to do genetic testing? Can you just look at the cell population in some way? Can you offer any wisdom there?
Dr. Hedberg: Yes. Let's just talk about the testing. And just on a side note, the Epstein-Barr virus panels that are offered through the major labs like LabCorp and Quest, et cetera, they're looking at the three main things which is the nuclear antigen, the viral capsid antigen and the early antigen. Unfortunately, in their standard panels, they leave out the IgM from the nuclear antigen and then early antigen. So when I started doing these testing, IgG and IgM for all three, and so I'm seeing a lot more activity when I do that. Yeah, you can do, basically, just a CD4/CD8 ratio and what you'll see, and this is one of the things he talks about it in his papers, there's one common theme among almost everyone who has autoimmune disease and that's a low CD8 count. So their CD4/CD8 ratio is elevated. CD4 is high,
