For those with CFS who have done 23andMe testing...

Discussion in 'Fibromyalgia Main Forum' started by rockyjs, Jul 28, 2014.

  1. rockyjs

    rockyjs Member

    We have known for years that I have some sort of immune deficiency that makes me very susceptible to viruses and chronic EBV, CMV, Parvo and other infections. My immunologist was not sure about the exact cause, but I have been working my way through my 23andMe raw data and looking for pathological mutations related to T-cell function.

    A few weeks ago I found the answer. I am compound heterozygous for (meaning one mutation on each of two SNPs) that cause Severe Combined Immune Deficiency, often referred to as the Bubble Boy Disease. My particular mutations only affect T-cells, not B or Natural Killer cells, so I can fight bacterial infections, just not viruses.

    For those of you who have done the testing and know how to check your raw data, here are the two SNPs:

    rs1494555 Normal is AA (TT on dbSNP) Mine is AG
    rs1494558 Normal is CC (GG on dbSNP) Mine is CT

    I am curious if any of you have these variants. SCID is a recessive disorder, so you would have to have two (in same SNP or two different SNPs) to have symptoms. I communicated with the top researcher about this and he said that although the most serious cases occur in the first six to twelve months of life (the only treatment is a bone marrow transplant) they are now recognizing that many survive and have undiagnosed SCID. It seems to be related to how much residual protein the defective receptors can produce and that varies.

    It doesn't really change treatment options for me (although children usually get bone marrow transplants) but it does help my doctors understand how critical it is that I minimize exposure to viruses and how important infection control is if I am in the hospital. For instance I got parvo virus from a blood transfusion because donors aren't screened in the US. When CNAs would come in to take check vitals they never disinfected the pulse oximeter. So they go from room to room, putting the clamp on index fingers of patients with all kinds of infections and never think about how they are spreading disease. When I go to the dentist I would always get a flare of Epstein-Barr. They wear gloves to protect themselves, but don't think about all the things they touch like drawer handles, lights, and other non-sterile objects that could spread germs.

    I asked some friends in a support group for Mast Cell Activation Syndrome to check their results and several had the same mutations as I did. Most of us are very sensitive to chemicals, fragrances, foods and medications. I suspect the heightened histamine response and mast cell proliferation is a protective effect when you can't make adequate lymphocytes to fight infection. The mast cells line mucosa and are one of the first lines of defense against pathogens.

    If you do have variants on the above SNPs, the next step is to get two tests to look for a deficient immune response. These are the test descriptions from Mayo Medical Laboratories, but most major labs offer them.

    Lymphocyte Proliferation Test

    T-Cell Subsets

    If you want to read more about the particular mutations, this is the OMIM database listing for the Interleukin 7 Receptor gene. The two SNPs above are the first two allelic variants listed in the description:


    Another good reason to get this documented if you have the variants is so that your doctors will realize how dangerous it can be to prescribe immunosuppressive drugs.

    It's nice to finally have a documentable reason for the chronic EBV infections (and other persistent viruses) and the constant fatigue they cause. The original SCID bubble boy, David Vetter, actually died from EBV. They did a bone marrow transplant using his sister as a donor. However they didn't screen the cells for Epstein-Barr and he developed a massive infection from the transplant and died two weeks later.

  2. victoriaz

    victoriaz Member

    rs1494555 Normal is AA (TT on dbSNP) Mine is AA
    rs1494558 Normal is CC (GG on dbSNP) Mine is CC

    So for me this isn't a problem.
    Though I also have sensitivities to chemicals, perfume, smoke, etc.
    And I do have low IGG 1 results on bloodwork, which I think is related to my viral infection problems.

  3. ME-sweden

    ME-sweden Member

    What happened after you found out that you had the mutation in both genes? I have the same mutations that you have. Did you get any help from your doctor? I have me/cfs since three years after a pneumonia.
    Hope to hear from you.

    Best regards
  4. rockyjs

    rockyjs Member


    We have run many other tests since then which confimed the immune deficiency including a B cell panel which contains naive and memory b cells.

    That raised the question of another type of gene mutation which is the Interleukin 21 receptor, and I also confirmed mutations in that gene (IL-21R). My serum immune globulins are fine and so are serum complements. So the problem for me is that the antibodies can't get the signal to the T cells and B cells to increase production and fight the virus. It's especially a problem with viruses like EBV and CMV because they use B cells as a host for replication.

    In some immune deficiencies it helps to get immune globulin therapy. In my case it doesn't because I already make plenty of antibodies. It's like an alarm going off at the fire station, but the firemen can't wake up to go fight the fire because they are wearing earplugs (the gene mutations).

    I have tried to many different things to try to clear viruses. Most immune boosting supplements don't work and in fact make me feel worse. I have seen some improvement with royal jelly in honey (1 tsp per day), Transfer Factor (I use the bovine colostrum) and pure bioactive unheated whey powder. What helps me the most is homeopathic nosodes for the particular viruses. I get mine from a company called DesBio in the US but in Europe I would recommend Remedia Pharmacy in Austria. I always use either C30 or C200 dilutions. On their website they have a nosode for EBV and also one for mycoplasma pneumonia which might be helpful for you.

  5. ME-sweden

    ME-sweden Member

    Hi Jan,
    Thank you for your answer. Do you know what IL21R genome (SNR) I should look for in my genome data, there's quite a few there. Six of them are not paired or what I should call them (CT instead of CC).

    Many thanks for your support.

    Best regards
    Last edited: May 8, 2016
  6. rockyjs

    rockyjs Member

    This is the SNP on IL-21R where I am homozygous for the variant:
    rs12934152 C:C (normal T, variant C)

    Having a variant on a SNP does not mean it will affect the production of the protein or enzyme. If you have one variant like CT it is called heterozygous, if you have two it is homozygous. If you have one variant on two different SNPs it is called compound heterozygous and that can have the same effect as a homozygous mutation. It all depends on whether the mutations are in a regulatory region and shown to either increase or decrease the production of the protein.

    Another clue with IL-21R immune deficiencies is that you will have tetanus antibodies, but you will have no response from your lymphocytes when they are challenged with the toxin. Same with candida on the lymphocyte stimulation test.

    23andMe only has a few SNPs listed out of the hundreds possible for that gene. I just lucked out and happened to have one of the known pathogenic mutations that was tested on their chip. It's still important to get the B cell testing to confirm or rule out that type of deficiency.

  7. ME-sweden

    ME-sweden Member

    Many thanks for your answer Jan! Have s nice day.
  8. acts31920

    acts31920 Member

    Is this correct? I am asking a question to understand. This is not a flame or a rant.

    The author of this thread said that:
    rs1494555 Normal is AA (TT on dbSNP)
    rs1494558 Normal is CC (GG on dbSNP)

    Is this correct?

    Mine was this flagged by a 23andme scanners as SCID combined immunodeficiency, autosomal recessive, T Cell negative, B Cell positive, NK Positive? I saw some research and it didn't list this as normal.


    Does anyone have links that show this to be normal?
  9. rockyjs

    rockyjs Member

    Both of those are listed as allelic variants associated with SCID on the OMIM page for IL-7R.

    Even if you have the risk alleles it is important to confirm with immune function testing like the panels I mentioned above. A researcher I spoke with said they're seeing more and more adults developing symptoms later in life rather than just the fatal form seen in children. They think epigenetics is a other words you may be able to make enough of the protein when you're younger, but environmental factors including chemical exposure, illness, etc may further inhibit the function and you will begin to have more severe symptoms.

    I just had an acute reactivation of EBV after a dental visit (which makes sense because it's a salivary virus). We ran a cytokine panel that showed very high levels of TNF alpha (the last one on the list) which is associated with acute mono/EBV. The problem is my T cells can't respond properly to fight the virus.


  10. rockyjs

    rockyjs Member


    IL7R, THR66ILE [dbSNP:rs1494558] [ClinVar]
    In a patient with T-, B+, NK+ SCID (608971), Puel et al. (1998) identified 2 homozygous mutations in the IL7R gene: a C-to-T (thr66-to-ile) transition in exon 2 resulting in a thr66-to-ile (T66I) substitution, and an A-to-G transition in exon 4 resulting in an ile138-to-val (I138V; 146661.0002) substitution. The patient was homozygous and both parents were heterozygous for both mutations. Each parent expressed mRNA only from the wildtype allele.

    IL7R, ILE138VAL [dbSNP:rs1494555] [ClinVar]
    See 146661.0001 and Puel et al. (1998).
  11. My results say.....

    Severe combined immunodeficiency, autosomal
    recessive, T cell-negative, B cell-positive, NK cell-
    You have the variants associated to the condition.

    555 is AA and 558 is CCto

    Attached Files:

  12. acts31920

    acts31920 Member

    So, Where is he best place to start asking the doctor's questions and for referrals? Which specialist? I have several due to multiple autoimmune issues.

    I have an infectious disease control doctor, but they have been struggling to understand the many different recurring infections that I get, and why it doesn't fit the normal standard diagnostic criteria.

    With you having gone through the testing, what is an effective method to getting where I need to go without overwhelming the doctors?
  13. rockyjs

    rockyjs Member

    Those are actually the normal alleles, not variants. It's not that unusual for third party analysis to be wrong (Livewello is the worst). Promethease is the only one I have found to be consistently accurate.


  14. rockyjs

    rockyjs Member

    The best way to get diagnosed is a good immunologist who specializes in immunology, not allergy (they're part of the same specialty). They can be hard to find. The Immune Deficiency Foundation has a doctor list. I can't post a link but you can find their website by searching.

    This is a list of the important tests to confirm an immune deficiency:

    Serum Complement
    Immune Globulins
    Lymphocyte Proliferation with Antigens and Mitogens
    Humoral Immunity Panel
    Lymphocyte Subset Panel (Total Lymphocyte Enumeration)
    B Cell Memory and Naive Panel
    Cytokine Panel (ARUP Cytokine 12)

    There are two sides to your immune system. If the humoral side is dominant (referred to as TH2) you will tend to have chronic allergies and mast cell reponses. If the cell mediated side is dominant (TH1) you will tend to have autoimmune disorders. While the tendencies can be genetic, there are things you can do with diet, medications and supplements to help balance them out.


  15. owdboot

    owdboot Member

    Hi Jan,

    I have just come across your thread. I have just had my 23-andme data returned, and have been suffering from persistent viruses for several years. I was starting to wonder if I had CFS and came across this site. When I read your entry, I thought I would check my 23andme raw data, and was gobsmacked to find I have the same mutations as you on IL-7 on those same SNPs.

    I have no idea what this might mean, or where to start. I am in the UK, so have to access any kind of lab tests via my GP or use private health insurance (which I do have, thankfully) somehow, although will require my GP to refer me in order to qualify for payment of any further tests.

    Clinically speaking, I had the usual childhood illnesses, but nothing out of the ordinary, as far as I know - chicken pox, mumps etc. As an adult, and particularly since having children, I have had recurrent viruses that seem to exhaust me for much longer than my husband (if he gets them) or my children (ditto). I often notice that stressful life events or situations can result in exhaustion, weird sore throats, swollen glands, a nasty back pain, and some herpes simplex type blisters appearing on my fingers or face. Some weekends I can sleep almost continuously for more than 24 of the first 36 hours (Friday night to Sunday morning). I work full-time in a stressful job and have to commute 2.5 hours each way to my workplace Mon-Thurs (work from home on Fridays)

    I had to have my tonsils removed in my thirties due to chronic tonsillitis (unsure if this is viral or bacterial-related). 5 years ago I got swine flu, followed by pneumonia. I have also suffered from periods of severe depression and am currently taking anti-depressants.

    I am desperate to know what I can do to help myself. I am getting pressure from work due to my frequent illnesses, and had been starting to feel that this is all in my head. Your post makes me think that perhaps I am not just making this up, but I don't really know what to do to explore the issue further.

    Any thoughts would be gratefully received.
  16. rockyjs

    rockyjs Member

    I would ask to be referred to an immunologist. Allergy and immunology are the same specialty, but most doctors go on to only treat allergy patients and not immune deficiencies. There is a good organization you might want to contact and see if they can recommend a doctor in your area. It's called PID UK (they have a website but I can't post the link). PID stands for primary immunodificiencies.

    I spoke with a researcher who said that even though those particular mutations aren't terribly rare in the general population, he's seeing more and more adults who survived (SCID is often fatal in children). They apparently had enough function of the receptor to eventually fight viruses, but as they aged the backup systems were less reliable and so they started getting chronic viral infections. You may also have another mutation that is affecting the function of your lymphocytes and making you more susceptible. I would ask for the tests that I mentioned above, especially the B cell naive and memory panel. This is what mine looked like:

    If your immune globulin profile shows an IgG deficiency, then you can get infusions to help, but this type doesn't really have a treatment other than avoiding sick people which is really not an option if you're working.

  17. owdboot

    owdboot Member

    Thank you so much, Jan,
    I will contact PID UK and see what I can do from there. And thank you for posting your test data also - that is so kind of you. I feel more hopeful that I can get some answers and some help.

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