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Overactive immune system, Neanderthal genes, and the Turkish connection

I read this today: "Also at the meeting, a team led by Michael Dannemann, a computational biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, reported that many humans have Neanderthal and Denisovan versions of genes that encode proteins called toll-like receptors (TLRs), which sense pathogens and launch a rapid immune response. Furthermore, cultured human cells containing the archaic versions tended to express the TLRs at higher levels than cells with the H. sapiens versions7. Although previous GWAS linked the archaic versions to a reduced risk of Heliobacter pylori infection, which can cause stomach ulcers, the variants were also associated with higher rates of allergies.

“Many traits that were adaptive 10,000 years ago might be maladaptive today” because of lifestyle, diet and other shifts, notes Rasmus Nielsen, a population geneticist at the University of California, Berkeley." http://www.nature.com/news/neanderthals-ha...

I had my genetic profile done by 23andme and they found I have 3.1% Neanderthal DNA (98th centile - max about 4%). Also that my mother's family (mitochondrial DNA) left Africa 50,000 years ago and so would have met the Neanderthals in the Silk Road area. (Behcet's is sometimes called the Silk Road Disease.)

A lot of people aren't diagnosed because they aren't Turkish so doctors will not consider the diagnosis. I have no doubt it is therefore under-diagnosed.

My maternal haplogroup is U5a1, but I have a lot more Neanderthal DNA than my mother so that came from my father.

It's an interesting thought that our problem may not be anything more than a hyperactive immune system. If anyone else is interested in following a possible genetic connection of our problem to the Neanderthals then I'd like to hear from you.

richard1
moderator

Hi Jane

There was an interesting article on Genetics and Behcets.

Some modern humans carry immune genes that originated in Neanderthals and a related species. But these genes may have come at a price

Interbreeding with Neanderthals (above) and Denisovans may have brought short-term health benefits but long-term problems.

One question seemed to hang in the air more than any other when scientists first turned the powerful techniques of modern genetics on the fragile and damaged remains of ancient humans: did we or didn't we? Have sex with them, that is.

The answer came after years of painstaking work, when material extracted from the leg of a Neanderthal and the fingerbone of a Denisovan, an apparent sister species, yielded readable DNA. It turned out that most of us have some of their genes. The Neanderthals contributed up to 4% of modern Eurasian genomes, while the Denisovans contributed roughly 4-6% of modern Melanesian genomes. That doesn't happen by holding hands.
And so the scene was set. Hundreds of thousands of years ago, early humans in Africa split into several groups, among them Homo sapiens, Neanderthals and their apparent sister species, the Denisovans. The Neanderthals headed for West Asia and Europe, the Denisovans to East Asia. Our ancestors left Africa much later, and arrived in Eurasia where the others had set up home. Cue amorous encounters, and surely a fair amount of less than amorous contact.

But the question of whether our ancestors mated with these other human-like groups was always just the starting point for a line of inquiry. With interbreeding now well-established the intriguing question is, what came of it? How did our ancestors' antics shape the people we are today?

A glimpse of the legacy of those ancient encounters is revealed in a study reported today in the US journal, Science. An international team of scientists, led by Stanford University, scoured the Neanderthal and Denisovan genomes for gene variants that are central to the immune system. These genes belong to a group known as the HLA class I genes, which govern the body's ability to recognise and destroy dangerous pathogens.

By comparing the HLA genes of modern human populations with those from Denisovans and Neanderthals, the scientists identified a handful that could be traced back to ancient sexual encounters between the groups. One variant, known as HLA-B*73, likely arose in modern humans after cross-breeding with Denisovans. The variant is most common in West Asian populations, the region where the mating probably happened.

The Neanderthals contributed a string of HLA gene variants, or alleles, to the modern Eurasian population's gene pool, the study found.

There was good reason for Neanderthal and Denisovan immune system genes to have spread through the populations of modern humans who encountered them. Both Neanderthals and Denisovans had established themselves long before modern humans arrived. Their immune systems had adapted to the threats of the local environment. When those genes crossed into modern humans, they conveyed an advantage. Natural selection took care of the rest.

But the scientists think there was a downside. Inheriting Denisovan or Neanderthal immunity genes will have helped modern humans to fight the diseases of the day, but beyond the age of reproductive maturity they might have a more harmful effect, turning our immune systems on ourselves.

Paul Norman, a co-author on the paper, put it like this: "There's enormous genetic variation in people's immune systems and that can control how different people fight different diseases. This could go some way to explaining why some people are better at fighting some infections than others, but we think it also goes some way to explaining why some people are susceptible to autoimmune diseases."

Autoimmune diseases are conditions that arise when the immune system turns its firepower on the body, usually when it mistakenly identifies the body's tissues as foreign, and so potentially dangerous.

"The vast majority of autoimmune diseases have been shown by genome-wide association studies to be associated with particular HLA alleles and we find a couple of those in Denisovans," Norman added. "So it looks to me like modern humans have acquired these alleles, but we weren't kind of prepared for them, we hadn't grown up with them, and in some circumstances, they can start to attack us as well as the viruses and other pathogens."

The group is now investigating a gene variant called HLA-B51, which came from cross-breeding with Neanderthals and has already been linked to Behcet's disease, a rare and chronic inflammatory condition.

How else might immune genes inherited from Neanderthals and Denisovans affect the health of modern humans? The question is intriguing and will differ from population to population.

Regards

Methotrexate

Anyone here have experience with methotrexate? Side effects? How much it helped / didn't help? I just got prescribed, doctor wants me on it now. Started me on 10mg oral dosage. Not familiar with really anything besides colchicine and glucocorticoids...

Hi sunset, thank you for your reply. I'm trying to figure out what you're saying though. The English translation isn't making that much sense.

robpleticha
moderator

Hi Sunset,

I think you used Google Translate from Turkish--English and posted it there...? Unfortunately, Turkish isn't one of the five languages we currently support, but we'd like to help. If you share your post in Turkish, we can help translate. Please write in Turkish if you would like.

Thanks.

Thanks Robert, I will write letters Turkish.

Evil Eye

Last year I noticed I was seeing double and the optometrist prescribed new glasses with prism which helped. I had uveitus few years 'ago so I was a bit upset. He didn't see much inflammation but my eyes seemed dry. I started using drops every day. A few months later I started seeing double again, I went to a Neuro- optometrist who said the optic nerve was fine and said to use more eye drops because I had "pitted" lenses. I ended up going back to the regular eye doctor. He remade the lenses at a higher per and maxed the prism. I was back in a months cause I still had double vision. I was referred to physical therapy for my eyes. She told me she was positive it was my unknown autoimmune issues that were causing the double vision. So I started the old doctor rounds. Thats when the clinic Nurse Practitioner in rhuematology studied my past files, ran blood work. I told here I was always negative and most doctors wouldn't believe me until my first episode eye and retinal inflammation. I was dealing wish symptoms getting worse by the week, plus the mouth ulcers, fungal infection in my ears. I didn't tell anyone of my privates getting abcess's. Those were getting worse as well. So the question I have is with seeing double, is it my brain that is affected or my eye muscles? Will therapy do any good? Each session would cost me $100 a visit and the therapist states it would be weekly for up to a year! I can't afford it but I put in a financial assistance request. If it wont then I would rather not have the money spent. I am frustrated too because everyone is running for books. Finding doctors for treatments is difficult if not impossible.

Sorry! I have problems with my eyes double vision,ulcers,black spots in my central vision.i have no peripheral vision at all.I fall a lot.walk into things trip over nothing. have they done a ct scan? It may be your brain.Good luck.

Thanks.no recent ct but I visited with a neurologist it took 6 months to get an appt for. He and my Rheumatologist are disgussing new treatment. My cognitive function is worsening. I'm having trouble thinking between times? Timelines? My food isn't being pushed thru very well for digestion either so possibly the autonomous nerves are being effected. I'm scared of being helpless. I feel isolated and I don't know if my family realize how serious it is. My eye dr feels helpless too. I saw it on his face last visit. He said he will do what he can until he can't. It was unspoken that I'm losing my vision too. Well, I'll be seeing the doc next wed. I hope the insurance doesn't cause problems or delay treatment. Fingers cross!

Thnks Jane, I did do the diet food trigger thing and nothing different. My parents both have autoimmune problems. Dad died from a lung biopsy that triggered his idiopathic pulmonary fibrosis to destroy what lung function he had left. He had early heart problems but nothing else was detected. Mom has Addisons disease, cardio myapathy or what have you plus other autoimmune issues. This year she has had 2 major strokes and couple small ones. These have been going on for years. Yes for my family it is genetics. My daughter and son both have food allergies and digestive issues. My daughter has anklesponditis as well and as a child had an idiopathic meningitis scare. I don't drink milk but I can tolerate yogurt. I am allergic to mold and fungus, dust and feathers. At least I can still eat chocolate! I can tell the difference most the time when I eat chocolate on my tongue... it has its own creaminess to the texture, sweet but not grainy, not slimy thank god! I still enjoy that

Back pain and Behcet's

Does anyone else experience crippling lower back pain with Behcet's? I will have my second full dose Remicade infusion next week. I have heard good things about Remicade. Has it helped decrease back pain for others? I hurt so bad I take Zofran so I do not throw up. I am trying to stay away from narcotics. Has Remicade helped patients w/back pain?

Yes I have back pain if I have one of my Behcet food triggers. And used to have it for days/weeks at a time. I found that going for a long walk often made the pain go away.

Hello, my name is Mindy. I've been on Remicade before (about 6 months ago) and I found I did help with BD pain and other symptoms, like mouth and genital ulcers, neck and head pain etc...
However, I had to stop for now because I was getting horrible kidney infections from the Remicade infusions. But I'm so very hopeful it works out for you!!! You'll be in my thoughts and prayers!! Xoxo

Hi Lauren,
I have not had Remicade. I haven't had a confirmed diagnosis of Bechets yet, however I am certain I have it. My rheumotologist believes I have it as well, however for some reason he hasn't diagnosed me yet. I have had chronic lower back pain for a few years now, and sometimes I have gotten extremely painful spasms that make me not be able to move. I had no idea chronic back pain could be from Bechets. So far nobody has been able to find the cause of my back pain. I went to physical therapy for about 6 months or so. It sort of helped; the stretching felt nice. I have had xrays done during a spasm, and my doctor had come to the conclusion that my lower spine was being pulled straight by my muscles, hence the extreme pain. Other than that thought, I have just lived with it and not questioned it. I feel bad myself and others have to live with this, but it's nice to know I'm not alone. I hope you are feeling well!

Feeling dizzy / lightheaded / out of it / shortness of breath before flare up?

Anyone notice these signs before a flare? I don't know if it's just me or not, but reflecting back before some of my flares, I feel a bit woozy, really weak feeling. It's hard to explain the sensation, but it's similar to having low blood sugar or something like that (but it's a different feeling). It's like a sign it's coming on.

It reminds me like someone has blown a bunch of smoke in a room. I actually described it that way one time. The brain fog hits - it's hard to think clearly. Generally feel bad all over - often accompanied by joint pain. When I feel "woozy" - it's like my blood sugar is messed up, even though it tests normal (my blood pressure is relatively normal as well). Then I start feeling really out of it. When the "rubber legged" feeling starts it's the worst, its like you're uncomfortable in your own skin. The shortness of breath will come and go very periodically and randomly during this period of time. I also notice I will feel unusual sensations in different places of my body when it happens. A horrible experience all around. I believe it is a sign of all around systemic activity. It is very easy to mistake what is going on for something separate. It becomes all too clear though when the "usual" symptoms (mouth ulcers, genital ulcers, eye issues, skin problems) become more frequent. I know I'm reiterating myself a bit, but it's good to see others who feel the same things. I can't really comment if I'm stuffy or my lungs are junky or not, because I've had allergies and sinus issues (congestion, stuffiness, a sinus infection every blue moon) forever.

It is so helpful to hear you both describing this because I feel this way a lot of the time and I have been considering everything as separate symptoms and treating them separately too. I have tested with borderline blood sugar so I think it's that but when I eat something it is still there. When I stand up, my legs do feel rubbery and I feel like the energy is draining out. I do feel woozy and dizzy but I thought it was from standing up too quickly but it lasts for a while so it can't be. I do feel like I am wandering around in a fog. I told the Dr. I was spaced out all the time. I am stuffy a lot. I have sinus issues but this is much worse. I am taking a lot of pseudofed. I have asthma anyway so hard to tell about shortness of breath. I am waking up with bad headaches and neck aches.. It is systemic since I am starting to get mouth ulcers again, I usually have genital ones.
Thank you both for sharing that! It is very helpful knowing that it isn't separate.

Jenny, I am so sorry you were sick and lost everything in the fire! I am glad everyone was ok!

Thanks Behcet 710

Julia

I am really interested to read what you're saying about blood sugar. Beginning in my 30's, I found that if I waited until after 7pm to eat in the evening I would get a STARVING sensation. On many occasions we were going out for a meal and I would ask my husband to stop so I could buy something to eat. If I didn't then I would get terrible pain in my stomach and end up on the sofa or upstairs for the evening. Weird thing is that once the pain and hunger started NOTHING would make it go away! Even if I forced myself to eat a huge meal I would still be starving.
As long as I stay off anything containing milk in any form that doesn't happen. Now I know what real hunger is, and it isn't anything like the starving feeling I used to get.

Speculation : is behcet's at least partially affected by histamines, dysbiosis?

I've read many stories from many behcet's patients saying that they complain about food sensitivity, stomach problems, and them losing their appetite heavily. This is something I went through, and tend to go through around the worst flare ups. Some patients report finding relief through certain foods, probiotics, and taking antihistamines. I also find relief after I take an antihistamine.

A lot complain about a bacterial or viral infection at some point before the diagnosis.

What I'm wondering if something like this : if some type of infection causes an immune system reaction, triggering it to go chronically "out of wack" long after the infection is gone, causing behcet syndrome. Maybe people with HLA-B51 genes are more sensitive to this type of reaction? Maybe this is why some people recover when they're older in life and maybe this is why people have different symptoms?

I already feel my gut has significantly improved when I control my diet and take a probiotic. It's known that the gut bacteria interact with the immune system, so maybe that's the reason for some improvement there. I am thinking about taking an antihistamine daily before bed to see if I have improved results. I believe when my gut issues are at their worst I might be having a type of histamine reaction at times. I will ask the doctor about this next time, maybe he can check my histamine levels.

I found this study also : http://www.ncbi.nlm.nih.gov/pubmed/7250460

Interestingly enough I also found someone else who thought of something similar too : https://healthunlocked.com/behcetsuk/posts...

This is all just my personal guess and speculation on the matter. I could be 100% wrong. Will see with time if antihistamine improves anything.

Anyone else think something similar?

I know the other group I was in they took a poll and a lot of us had mono. so it could be a good possibility.

For ulcers oral or genital you should ask your doctor an RX for Fluocinonide. It's a steroidal gel. It's Knocks them down big time. It's a miracle for a mouth full of ulcers because it gets them to go away not just numb the pain.
Good luck!

thanks! I have grown use to them I think.Is it not sad when you have grown used to something painful? spring is the worst for me the pollen and season change I flare every spring.

Any specific diet?

I really want to start eating healthier, and I was wondering if anyone has made any specific diet changes that has helped them. Are there any food someone with Bechets should avoid, or any that seem to be helpful? This is a very generic question but I figured it couldn't hurt to ask. Thanks in advance for any advice or suggestions.

Thank you for your advice. :) I dont eat much nut products, and I really cant eats nuts at all right now. I just got all 4 of my wisdom teeth out 3 weeks ago and have been having a very rough healing time. The nerve in the left side of my jaw running from my chin up to my ear has been in quite a bit of pain. It's finally getting better though, thank goodness. I'm wondering if the Bechets, if in fact I do have it, is causing the slow healing and overreaction of the injury to my mouth. I will definitely look into the food with the alkaline phosphatase (unsure if I spelled that right?).

martacampabadal
moderator

Hello,

You should check this conversation "Food sensitivities with Behçet's". It has lots of interesting comments: https://www.rareconnect.org/en/community/b...

It almost certainly has caused the slow healing. please be careful! I had an ulcer in my mouth. it got infected and tunneled along my jaw all the way to my lip. needless to say I no longer have feeling on the right side of my face to the jaw.I wait until I know I am in a flare to have dental work done,change meds,anything that will disturb or agitate the disease.Last time I made an appoint. had 4 teeth pulled and reconstruction work done on 18 teeth at once.I value my good days.Good Luck! pm me with any questions!