My LLMD did NOT tell me that my 8-number genetic combination may be a predictor for severe rheumatoid arthritis...perhaps I am wrong about this part, since I have not had the training required to understand all the genetic combinations --
it really bugs me that we could practically earn medical degrees with all the research we have to do ourselves!
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SForsgren
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Yes, yes, and yes. You CAN get better. It suggests you need to focus as much or more on detox and drainage than killing. It can help you put a good treatment program in place, but I do not believe you cannot get well. I am 4-3-53 myself.
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
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I just received my results from a HLA genetic test I had.. I have no clue how to read the results.. Can anyone explain this to me?? Iam so confused
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CaliforniaLyme
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I don't know whether you will get all the way well or not, a good portion of our support group has to stay on "maintenance" abx or they decline. Some people have been on abx for decades but lead full, wonderful lives.
Because so few have had tissue types tested it is impossible at this point to tell what role that really plays. There is NO evidence this means you need to focus on one thing or another- in fact- what you were just told could be the opposite of what you need to do. Please run treatment decisions before a LLMD!!!
Best wishes, Sarah
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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Greatcod
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Interstingly, Steere shows that HLA-DR4 haploytpe underlies treatment resistant Lyme athritis because of an autoimmune response taking place. But he makes no mention, and would deny that symptoms other than arthritis are Lyme related.
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cottonbrain
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Kelly, I hope I didn't sound like I knew what I was talking about on these genetic variations! I had to go to a lot of sites to glean what little i could understand.
Here's what my results showed, in case it will help somebody illuminate this:
LOCUS ALLELES
DRB1 0401, 1104
from what i understand, the DRB1, combined with the last 4 numbers 1104 may be a predictor for severe type of RA.
the number 04 under alleles indicates HLA-DR4.
I am sorry, but i did another search and did not find the sites where i gathered this info. I think I had to google a combination of HLA ALLELE STUDIES -- something like that.
Maybe Scott can shed some light on reading your results?
Remember, I am only guessing, based on haphazard research -- I am still trying to figure it out and my LLMD pretty much whitewashes all this -- one reason I am switching LLMDs.
Thanks, everyone, for your comments.
Kelly, I am interested in learning what your LLMD says about treating the HLA DR4 peeps.
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adamm
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So would the fact that that the doxy I took right after my bite
and the triple therapy I was on in december did nothing for me
indicate that I probably have this?
My musculoskeletal symptoms are really ultra mild.
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luvs2ride
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I happen to recall Scott stating time and again that abx have been and continue to be a part of his arsenal. He believes in a multifaceted approach to his illness. Much like Dr B.
I like a community where we support each other. There are a few here at lymenet who apparently don't.
Luvs
-------------------- When the Power of Love overcomes the Love of Power, there will be Peace. Posts: 3038 | From america | Registered: Oct 2005
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Cotton... I wish they had a website that explained all of this.. I actually asked my LLMD about the whole biotoxin thing.. he knows alot about it and pretty much said it was up to me if I wanted to start taking the binder pills.. he really wasnt all for it or against it.. I think iam going to give it a try.. It cant hurt
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cottonbrain
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getting back on track:
adam, I would NEVER venture a guess on whether you have the genetic variation, or one of those that Scott mentioned. I'm not familiar with those.
Perhaps it is possible that you just haven't found the right cyst buster yet?
However, if you are concerned, please have your doc order the test! ANY doc can do it; it does not have to be your LLMD, and it does not have to be any special lab.
although probably only your LLMD can read the results, alas.
If there is anybody out there who has some more advice on what to do if you have this variation, help please!
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cottonbrain
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adam, i forgot to mention -- the HLA-DR4 genetic variation is not uncommon.
I think as many as 20% of 'normals' have this (?)
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Greatcod
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Don't know the number, but it is quite high and very common.
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When we took my Gdd to see Dr. J in Ct. he ran the HLA DR4 gene test on both my daughter and Granddaughter. So it must have something to do with treatment if Dr. J is running this test. Dr. H had told Dr. J that my dd was one of his more difficult to treat cases.
I think Dr. J just did the test on my dd so he could shed a bit of light on my dd's case for Dr. H.
This was back in 9/2005. She is still one of his difficult to treat cases and and YES, she does have the HLA DR4 gene. Her daughter my Gdd doesn't. Thankfully.
She has only gotten worse since starting treatment 3/2005. Can't explain it, don't know why but we are trying . She just had more genetic testing done for more of the HLA genes. There was a thread on it.
Something about when antibiotics fail. I can't read the test results......WOW, it just looks like lots of numbers. Dr. H can, he said he has to get his book out...........LOL, he is such a wonderful guy.
Supposidly people with these HLA genes can't detox. You have to go about treatment in a different way from others without it. Detox then start over with killing off the Lyme and co.
Oh, and I read that people with the HLA DR4 gene have a physical symilarity. If you put your arms up like you are flying, and measure from finger tip on one arm to the other, then measure your height. Your arm span is usually more than your height if you have this gene.
I don't know how scientific it is but the 4 people that I know of that have it all have very LONG arms and they all have the HLA DR4 gene.
Hugs,
-------------------- ICEY Posts: 468 | From Las Vegas NV | Registered: Jun 2005
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cottonbrain
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Icey, I always thought everybody else just had SHORT arms! (that fact is remarkable)
I sure hope your daughter sees some improvement--did she try IV as well as oral abx? And did she detox first, as you say is recommended?
Do you remember her detox protocol?
Thank you so much for the info. I wish your daughter and granddaughter well.
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I also have the DR4 genotype, I do feel like it makes Lyme harder to treat. I was dx with JRA at 13yrs old (now 48) Dr K, in CT, said 30% of the population has this type but not all have Lyme.
He put me on plaquenil for this problem. Since I have Band 31(used in the Lyme vaccine) it will trigger the DR4 gene. He said "no matter how low I get the Lyme levels, Band 31 will always trigger the DR4"
I also have the Detox problem, long wingspan (Dr Shoemaker) CSM does help me feel better. Some are some genetically better off than others. Some say it doesn't make a difference - I say they are the ones without the DR4
PS - I think Scott does a great service to many with his articles and website. Posts: 315 | From USA | Registered: May 2005
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cottonbrain
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lITTLESPROUT, i am so sorry to hear that the hla dr4 is causing so many troubles -- for you and everyone else who has it (including me).
I am curious, what is CMS?
How much do you think the Plaquenil helps?
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lymebytes
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From what Schaller says in the followng link: The HLA-DR4 test determines aggressive Lyme arthritis.
A different 5-part HLA test is able to determine how well you can remove the dangerous biotoxins.
cottonbrain
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intriguing website.
Do you have any idea what his detox methods are? He is playing them close to the vest.
I've heard of LLMDs who do IV chelation -- i wonder if that's what he's about?
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SForsgren
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Treatment for biotoxins is likely cholestyramine, Actos, and possibly other binders. Chelation is generally for metals and I am not aware of chelation per se that is for biotoxins that are the result of HLA susceptible genetics.
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
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CaliforniaLyme
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The BIG picture is intresting!!! They have learned a lot about haplotypes but there is a lot still to learn-
BAD NEWS: the one allergic reaction or side effect that happens more frequently with HLA DR4 is allergy to latex! (which I have, hmm*)!
HLA DR3 is associated with greater toxicity
HLA DR9 is associated with allergic reactions to penicillins-
GOOD NEWS: HLA DR4 has been found to convey an actual DECREASED toxicity re gold- it is considered to have a PROTECTIVE effect re toxins in that regard!!!
OTHER GOOD NEWS: HLA-DR4 is associated with a diminished risk of the development of chronic myeloid leukemia (CML)!!!
MAYBE GOOD NEWS: In mice HLA DR4 is protective against chlamydia!!!!!!
GOOD NEWS: Certain subtypes of DR4 are less likely to get DIABETES!!!!
So don't feel cursed!!! It may be a blessing in the grand scheme of life*)!*)!
If you were HLA DR3 you WOULD have to worry about a greater need to detox- !!!
Interestingly, HLA DR4 also means if you ever get diagnsoed with Stills Disease you will be not treatment resistant but more treatment RESPONSIVE (weird, eh?) Methotrexate works better in HLA DR4 people for that than in other people!!! And because of that they have actually been injecting RA patients with a DR4 BOOSTER shot to prep them for treatment with methotrexate!!! Cutting edge stuff!!!
QUOTE: The most interesting finding was the low incidence of DR4 in patients who developed adverse reactions to gold, suggesting that DR4 positive patients may have some degree of protection against gold toxicity.
*********************************************
1: J Rheumatol. 1984 Jun;11(3):358-61.Links
HLA antigens and toxic reactions to sodium aurothiomalate in patients with rheumatoid arthritis.
Bensen WG, Moore N, Tugwell P, D'Souza M, Singal DP.
HLA typing studies were performed on 60 consecutive patients with seropositive definite or classical rheumatoid arthritis (RA). Patients were treated with gold and were followed for a minimum of 18 months for identification of adverse reactions to gold therapy.
HLA-DR3 was increased significantly in patients who developed gold induced rash, proteinuria or thrombocytopenia.
On the other hand, the incidence of HLA-DR4 was lower in patients with these adverse reactions.
Our results demonstrate that patients with RA carrying DR3 are at a higher risk of developing adverse reactions to gold.
The most interesting finding was the low incidence of DR4 in patients who developed adverse reactions to gold, suggesting that DR4 positive patients may have some degree of protection against gold toxicity.
PMID: 6234391
1: N Engl J Med. 1980 Aug 7;303(6):300-2.Links HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis.Wooley PH, Griffin J, Panayi GS, Batchelor JR, Welsh KI, Gibson TJ. To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3.
The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive.
No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications.
Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.
PMID: 6770269
1: Ann Rheum Dis. 1985 Sep;44(9):621-4. Links
HLA antigens and toxic reactions to sodium aurothiopropanol sulphonate and D-penicillamine in patients with rheumatoid arthritis.
Perrier P, Raffoux C, Thomas P, Tamisier JN, Busson M, Gaucher A, Streiff F. One hundred and forty-one patients with rheumatoid arthritis treated with aurothiopropanol sulphonate or D-penicillamine, or both were examined for HLA antigens to investigate the genetic influence on the occurrence of different adverse reactions during therapy. All 13 patients possessing HLA-DR3 had toxic reactions. The relative risk for DR3 positives of developing skin eruptions or proteinuria was calculated to be 10.5 times and seven times respectively that of DR3 negatives. The incidence of DR7 antigen in 94 patients with toxic reactions was significantly decreased (11% compared with 28% in controls) suggesting a protective role for this antigen.
PMID: 3876081
1: J Rheumatol. 1984 Oct;11(5):610-4.Links HLA antigens and toxicity to gold and penicillamine in rheumatoid arthritis.Scherak O, Smolen JS, Mayr WR, Mayrhofer F, Kolarz G, Thumb NJ. One hundred sixty-eight patients with rheumatoid arthritis treated with chloroquine (n = 87), gold salts (n = 133) and/or penicillamine (n = 77) were investigated for possible associations between HLA antigens and toxic reactions. Patients with 2 or more side effects to gold and/or penicillamine had a significantly increased frequency of antigens HLA-B8 and DR3 compared to patients with one or without adverse reactions. Proteinuria to gold or penicillamine was significantly associated with HLA-B8 (relative risk [RR] 4.2) and DR3 (RR 14.0) whereas nonnephrologic side effects to gold or penicillamine were associated with B7 and DR2 (RR 3.5 and 2.8). Patients with skin reactions to gold had a significantly greater frequency of HLA-B7.
We found no correlation between chloroquine side effects and any HLA antigen.
The results suggest a genetic predisposition to toxic reactions to gold or penicillamine based on an immunologic dysregulation.
PMID: 6439866 1: Chin Med J (Engl). 2006 Mar 20;119(6):458-66. Links HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins.Yang J, Qiao HL, Zhang YW, Jia LJ, Tian X, Gao N. Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450052, China.
BACKGROUND: Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin. METHODS: Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction. RESULTS: Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, chi(2) = 4.057, P = 0.044).
CONCLUSION: HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.
PMID: 16584643
1: J Rheumatol. 2000 Aug;27(8):1855-63.Links
Treatment of rheumatoid arthritis with a DR4/1 peptide.
St Clair EW, Cohen SB, Lee ML, Fleischmann RM, Lee SH, Moreland LW, Olsen NJ, Pratt PW, Yocum DE, Heck L, Winkelhake J, Holcenberg JS, Shulman MJ. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. [email protected]
OBJECTIVE: To determine the safety and potential clinical efficacy of primary and booster injections of a DR4/1 peptide in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.
METHODS. Subjects with active RA were enrolled in a randomized, placebo controlled, double blind, dose-escalating clinical trial of synthetic DR4/1 peptide containing the shared epitope. The primary injection of the DR4/1 peptide in alum adjuvant was administered at one of 3 doses, 1.3, 4.0, and 13 mg, followed by up to 3 or 4 booster injections every 6 or 8 weeks at the same dose. The primary outcomes were the occurrence of adverse effects and changes in measures of immune function. Clinical efficacy was assessed using the American College of Rheumatology 20% criteria for clinical improvement.
RESULTS: Fifty-three patients were entered into the trial, including 44 who completed the study. In the absence of any observations of a dose response to the DR4/1 peptide injections, the 3 dosage groups were combined for subsequent analysis into 3 groups: patients receiving DR4/1 peptide injections every 6 weeks, patients receiving DR4/1 peptide injections every 8 weeks, and a placebo group. At all doses and each dosing interval the primary and booster injections of synthetic DR4/1 peptide were well tolerated and did not produce any significant changes in lymphocyte counts or evidence of generalized immunosuppression. Analysis of clinical efficacy showed that the 6 week group had trends toward improvement in disease measures.
CONCLUSION: Primary and booster injections of the DR4/1 peptide containing the shared epitope were safe and did not broadly suppress immune function.
PMID: 10955324
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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The test I had done was the 5 part test that schaller refers too.. But he doesnt tell you how to read it.. Its just a ton of numbers.. He suggests that you have this specific test done, then leaves you hanging with no answers..
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adamm
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So can you get a duck to order it, and if so, what's the name
cottonbrain
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Thanks, CaliforniaLyme, for the great article -- i must confess, my neuro problems kept me from understanding allof it, but I will definitely give it a second perusal later.
i second adamm's question -- if you DO get the five part test, who do you get to interpret it?
Thanks so much, everyone, for helping to shed some light on this.
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I too had the HLA tests run... but Labcorp idiots "lost" the results. Amazing. LLMD says fax/letter never made it. All I got was a huge bill!
That was 3 months ago, when I was semi-mobile. We'll see when I get the trength back to the lab again.
All that I call recall through fuzzy brain is a memory of my LLMd saying is that this genetic (mutation/type??) means that a person has trouble detoxing, binding, getting the biotoxins OUT. I really didn't not get a sense that it's a fatalistic or determinator of hopeless prognosis.
Just a cue on how to fashion your treatment, more like...??
I wonder how HLA stuff relates to C4a and C3a levels, and all of Shoemaker's theories. I suspect some kind of a correlation b/w people with high levels of both. I am high with the C4a.... any thoughts?
Does anyoen know if people with other AutoImmune issues like Celiac's or Hashimoto's are overrepresented in this HLA group?
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luvs2ride
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My doctor has just run the test so I don't have the results.
She said if I am genetically impaired in my detox abilities, there is a medication I take the rest of my life.
Glad to hear there is a solution and sad to hear I may have to take a drug the rest of my life.
Luvs
-------------------- When the Power of Love overcomes the Love of Power, there will be Peace. Posts: 3038 | From america | Registered: Oct 2005
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cottonbrain
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This abstract, as far as I can make out, links HLA-DRB1 (my type) to RA:
Proc Natl Acad Sci U S A. 1989 December; 86(24): 10049-10053. Copyright notice
HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major susceptibility locus within the HLA class II region.
B P Wordsworth, J S Lanchbury, L I Sakkas, K I Welsh, G S Panayi, and J I Bell Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
This article has been cited by other articles in PMC.
Abstract Susceptibility to rheumatoid arthritis (RA) may be due to the presence of shared functional epitopes common to the HLA-DR beta chains of several RA-associated haplotypes. We have
obtained direct evidence for this hypothesis by using the polymerase chain reaction and sequencing the DRB1 and DQB1 genes from RA
patients. A highly conserved epitope present on DR beta chains of DR4 and DR1 haplotypes was found in 83% of 149 patients with classical or
definite RA but was found in only 46% of 100 control individuals (P less than 0.0001).
Two Dw subtypes of DR4 (Dw4 and Dw14) were associated with disease susceptibility but two other subtypes (Dw10 and Dw13) were not.
Sequence differences between these subtypes implicate those residues around the putative antigen binding site of the DR beta molecule in
the pathogenesis of RA. These data provide a basis for understanding host susceptibility to RA at a molecular level.
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cottonbrain
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here's an abstract linking Lyme Arthritis to certain outer surface proteins
SForsgren
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For those interested in information about HLA, please review Dr S book Mold Warriors or visit the site biotoxin.info which has much information about it. HLA DR4 4-3-53 is one of several dreaded genotypes that mean that the person is susceptible to Lyme and mold biotoxins. According to Dr. S., it is absolutely associated with a predisposition to mold and Lyme biotoxins and biotoxin illnesses.
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
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cottonbrain
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here's some info that may explain why detox may be important for HLA - DR4 types -- the flagellae that remain are band 41?
The post-infectious inflammatory hypothesis also is supported by several lines of evidence. For example, patients with Lyme arthritis who carry the HLA-DR4 or DR2 allele are more vulnerable to
developing a chronic antibiotic-resistant arthritis. Indirect evidence exists to support molecular mimicry as at least one possible explanation for persistent symptoms. For
example, the flagellin protein (on the tail of the spirochete) can generate antibodies that cross-react with myelin basic protein, thereby contributing to axonal dysfunction. Finally,
remnants of pieces of the spirochete may result in a persistent activation of the immune system, causing the production of interleukin-6, tumor necrosis factor, and nitric oxide. These
cytokines produce fatigue and malaise, two of the more prominent symptoms experienced by patients with chronic Lyme disease.
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SForsgren
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For those interested in HLA DR4 or the 4-3-53 genotype that Dr. S talks about, please visit biotoxin.info or read Mold Warriors. The 4-3-53 genotype is both mold and Lyme biotoxin susceptible and does suggest a need for detoxification and removal of biotoxins. Dr. S. explains his theories and work quite well in the book and on the web site. Be well
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
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TerryK
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CALyme - If you want to understand the thinking about toxicity and HLA DR4 you will need to research Dr. R S work. You won't find it in a pubmed article. Scott is correct about detox.
The appendix in the Mold Warriors tells one how to read the tests.
Terry
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cottonbrain
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UP
for how to read the tests. thx!
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CherylSue
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up
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