Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA(163-175)).
We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA(163-175) peptide to 14 DRB molecules.
Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic-refractory arthritis differed significantly from those in the 50 antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38).
7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA(163-175), whereas the other seven showed negligible or no binding of the peptide.
Altogether, 79% of the antibiotic-refractory patients had at least one of the seven known OspA peptide-binding DR molecules compared with 46% of the antibiotic-responsive patients (odds ratio = 4.4; P < 0.001).
We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease.
[ 10. April 2006, 05:58 PM: Message edited by: riversinger ]
Posted by snowflake (Member # 8950) on :
Interpretations please.
What does this mean?
Posted by bpeck (Member # 3235) on :
It says:
They had a sample size of 121 people who's major Lyme symptom was arthritis.
50 of these people had responded favorably to antibiotics, and 71 people did not respond to antibiotics.
Then they looked at the tissue types (HLA) for these two groups. Specifically looking further for the HLA tissue subgroup DRB. They found a higher rate of the HLA DRB subtypes in the 71 peopl who did not respond to antibiotics.
There are 14 HLA DRB subgroups. 7 of these showed some binding (from strong to weak) to OSP A.
So what they conlude is that:
50% of HLA DRB tissue types bind OSP A to some degree, and 50% of these subgroups do not.
SO - if you have Lyme arthritis that has not responded to antibiotics *and* and you are one of the 7 HLA DRB tissue types that bind OSP A - Then your tissue type may be the reason why.
Interestingly though - 50% of these HLAS DRBsubtypes **do not** bind OSP A- so that's JUST as important because HLA DRB cannot be the reson these people didn't respond to abx.
Barb
SO - the real bottom line is if you are a abx non-responder and you are HLA DRB - you have a 50/50 chance this is why.
Posted by riversinger (Member # 4851) on :
I found it interesting that I have two of the HLA types that they consider associated with antibiotic resistence. I am also, according to Dr. S's HLA subtypes, a postLyme neurotoxin type. He has a very different take on WHY this sub group doesn't get well.
I'll be curious what he has to say about this study. It has always been his theory that the people susceptible to neurotoxins lack the ability to bind the toxins by HLA. Possibly contrary to what these researchers are claiming.
However, all of the subgroups these researchers are claiming to be refractory are very likely to be part of Dr. S's subgroups of either postLyme or multisuscetibly neurotoxic. It isn't possible to tell for sure, because you have to know the full gene typing, not just individual HLA.
Posted by bpeck (Member # 3235) on :
River-
When you say antibiotic resistance- do you mean antibiotic nonresponsiveness?
So what is your Dr.s opinion on why 50% of the HLA DRB group doesn't respond to abx?
Barb
Posted by riversinger (Member # 4851) on :
Hi Barb! I meant the abx refractory folks the article was talking about. You are right, it isn't clear if it is resistent or non-responsive. For whatever reason, abx does not clear the symptoms.
I'm sure you know the theory of neurotoxins. He believes that the abx does work to kill the bacteria, but that the immune system then doesn't recognize the dead bacteria, or some neurotoxic breakdown portion. The neurotoxins are believed to cause some or all of the ongoing symptoms. He finds that people with these HLA types do well with the neurotoxin binders.
The point that is different is that S says that these gene types DO NOT bind well, this study says they DO bind at least the Osp A. Possibly what S is looking at is something completely different, and the same people bind Osp A and do not bind something else.
Posted by lpkayak (Member # 5230) on :
thank you for clarifing this...i remember when i COULD understand research...
i have the gene-dr4, i think it is.
abx got rid of my fatigue and foot pain-both severe and debilitating.
a yr of detox got rid of more transient pain
i am left with severe arthritis(dx with xray as osteo) in knees, thumbs and whole spine. (doc's say i'm young for this)---they say joints are "essentially obliterated-no cartilage to work with")
when stressed-physically or emotionally-i get other lyme symptoms back: numbness tingling, cognitive,eye pain, sharp joint/attachment pain,...but as long as i keep to my kete fighting routine i usually only have the "osteo" pain
is this osteo arthritis or lyme arthritis?
will more abx get rid of the osteo arthritis?
Posted by trails (Member # 1620) on :
How do you know or find out which HLA type you are?
Posted by trails (Member # 1620) on :
up
Posted by riversinger (Member # 4851) on :
trails, it is a labcorp blood test to find out what your HLA type is.
Posted by minoucat (Member # 5175) on :
river and barb -- just wanted to thank you for this thread, river, since I've been trying to understand the HLA-DR stuff.
And thank you, barb, for your exceptionally lucid and pragmatic explanations.
I have a friend who teaches science writing at OIT -- I think I'll email her your response as a model of what good science writing looks like.
Posted by lou (Member # 81) on :
Well, but Steere thinks anyone who doesn't get well in 3 weeks is a non-responder. For this reason, I think his data is too compromised by false assumptions to be useful in our treatment.
There may be something in this idea, but he is not a man I would trust to explore it. Until more reliable and unbiased research is done, I am not buying any genetic explanations.
Posted by bpeck (Member # 3235) on :
Mino: Thanks for the compliment.
Lou: After reading the early research of Wormser, Barbour and Steere (and a few others) I'll never understand why these guys seem to be biased now - especially with the way they interpret their own present data.
Is it really money? I guess.
And I guess untill someone actually finds a host/pathogen adapted aytypical variant (How's that for a mouth full??) that causes chronic problems - they're gonna ride that autoimmunity/ HLA DR/Band 31 kDa train into the sunset.
I won't be on it though.
Barb Barb
Posted by lymemomtooo (Member # 5396) on :
Lou, the Dr. S, that River is referring to is probably not Dr. Steere if you are referring to the reference of the Dr of Mold Warriers..Not sure Steere could make a boil on the backside of this Dr..But the study may make some of the ducks stop and think.
The Dr. S from Mold Warriers is a genius and has saved many people. I have a major issue with him but I would highly recommend him to save someone's life and I think his research will hold up to most scrutiny.
Posted by lou (Member # 81) on :
Thanks. I was actually referring to the article abstract that was in the first post on this thread, and Steere is a co-author of it.
If auto-antibodies are found in people with lyme, and if neural and thyroid and other tissues have genetic sequences in common with borrelia ketes, does this prove autoimmunity or infection?
As to the views of the other Dr. S, I have no comment.
Posted by Nebula2005 (Member # 8244) on :
IMO--
Dr. St---- et. al want to prove the autoimmunity theory so there would be the possibility of developing post-Lyme specific immune modulating biologic drugs, simular to Humira (used for RA), thus opening the research and development $$$$ taps.
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