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Monday, June 1, 2009

The Lyme Western Blot revisited

I get a lot of questions about Western Blot test results: Do I have Lyme?
The disease cannot be diagnosed by a blood test. The Western Blot test is one tool used to demonstrate that a patient has been exposed to Borrelia burdorferi. Period.
Testing for Lyme antibodies is much more complicated than testing for most other germs. Antibodies directed against most bacteria and viruses are determined by ELISA or IFA technology, and that it all that is generally required. The Western Blot was supposed to be a confirmation test used to validate a positive ELISA in the case of Lyme disease. Many of us who treat Lyme have found this to be inaccurate. The only other disease that I am aware of that uses this two tier approach is HIV. Some patients who test positive for HIV by the ELISA method are negative by the Western Blot method. These patients are false positive; they do not have HIV. Some patients who test positive by the WB method are ELISA negative and also do not have HIV. For the HIV test to provide accurate result the ELISA must be done first before the WB.

What is true for HIV testing is not true for Lyme testing. Nonetheless, many physicians cling steadfastly to this incorrect line of thinking.

A test is considered sensitive when it picks up all, or nearly all positive cases. Frequently, tests with high sensitivity also include some false positives. When this occurs the test is considered sensitive but not specific. A test is considered specific when a positive result is very accurate and can be relied upon for a diagnosis.

For many reasons, which have been discussed elsewhere, it has been shown that the current Lyme ELISA test is not sensitive. In other words it has many false negatives. This is why most physicians who treat a lot of Lyme disease skip the ELISA test and go right to the WB test.

It has been well established that seronegative(no antibodies) Lyme disease exists. One could debate how frequently this occurs, but in my experience it is quite frequent. This knowledge influences the interpretation of WB bands as will be discussed.

The spirochete has a lot of targets for antibody production. Areas on a germ which elicit the production of antibodies are called antigens. Antigenic regions on the bacteria are associated with the production of unique antibodies which target that specific antigenic region of the bacteria. In the WB test these are seen as bands which appear on the blot.

What is CDC positive? People are very confused about this. The CDC criteria for evaluating Lyme WB bands was created in 1994. Its purpose was epidemiological surveillance. It was never intended for use as or validated for use as a diagnostic tool. Those of us who look at Western Blots do our best to interpret the results based on our knowledge of what the bands represent. Since many patients are seronegative, the diagnosis of Lyme may be suggested when very few bands appear.

What is the IgeneX criteria? IgeneX has developed internal criteria which it reports as evidence of exposure to Bb. Basically if a patient shows two specific bands(in the same antibody class) the test is reported as positive.

The most commonly seen band is the 41 band. Most consider it sensitive but feel that it lacks specificity. I think the jury is still out on this one. It is not yet clear to me whether or not the presence of only this band can be used as supporting evidence of exposure to Bb. I don't think there are as many false positives as has been suggested by other authors. Both the CDC and IgeneX consider this band to be quite specific.

There are no standardized criteria for a positive Lyme Western Blot. This means that your doctor many interpret the results quite differently from other doctors. This includes LLMDS.

What we do know is that some of the bands are not very specific for Bb. I, like IgeneX tend to discount non-specific bands when viewing a report. When highly specific bands appear it is unlikely that their presence represents anything other than Bb exposure. Based on this thinking, many doctors may feel comfortable concluding that the test for Lyme is positive if few of these specific markers are identified on the WB test.

The very specific bands include: 93(region) 41,39,34,31 and 23. Some authors include the 18 band.

Whereas IgeneX will only call the test positive if the two specific WB bands are found in the same subclass of antibodies, IgG or IgM, this designation seems arbitrary and is of less importance to me. For example, If a patient has an IgG 93 band and IgM 23 band I feel comfortable that the patient result shows evidence of Lyme exposure.

In fact, the presence of a single, highly specific band(with the exception of the 41 band) may be taken as evidence that the patient has been exposed to Bb - a positive result. Again, it must be emphasized that there are no universally agreed upon criteria for the assessment of a positive or negative WB. Doctors who treat Lyme may all interpret these results through the lens of their own beliefs and experience and report differing conclusions.

The question then(at least regarding WB tests) is not doctor, do I have Lyme?
The question is, doctor is my Lyme test positive. First off, patients frequently ask: am I CDC positive. I then have to go through the process of explaining why this is not important. Ultimately I can only present patients with my interpretation of the results. This can end up being a bit unsatisfactory for the patient. Unfortunately, as is the case with most things "Lyme," answers to questions are frequently fuzzy. In the example given above, the 93 IgG and the 23 IgM are present. I would interpret this as positive result. There is no text or standard resource which patients can use to validate my interpretation. Ultimately it may come down to the doctor - patient relationship, and a patients comfort level with their doctor's interpretation. Patients should be aware of these complexities when requesting results from their doctor.

This is where the art of medicine trumps the science of medicine once more.

17 comments:

Soup2Meshugna said...

Wondering if I might be able to run my story past you as I am having quite a problem at this time and I am wondering if the old Lyme is acting up.

Thank You,

MJ said...

Why "with the exception of the 41 band"? this one is not as meaningful? It's curiosity, plus I have a positive 41!!!
THOUSAND THANKS!

ForgotTheMath said...

I'm the opposite of PatJ. I have 8 reactive bands (IGG:18,23,30,39,58,66.IGM:23,39) but neg on 41. I thought you had to have 41! Is the reaction a fcn of the tick that bit, the human that got bit, or the Bb strain used on the test?

Thanks!

Lyme report: Montgomery County, MD said...

I cannot respond to personal stories. I am available in my office for consultations.

I see there is a lot of confusion about WB results.

You do not have to have a 41 band!
One point is that other bands, including 23,31,34,39,93 are known to be more specific.

On the other you hand having only a 41 band does not mean you do not have Lyme disease.

Sometimes more bands appear after a Herx or treatment. Remember-Lyme is a clinical diagnosis. Lab data is only supportive of the diagnosis. Other antibodies such as the C6 index may be useful as well.

Michele said...

I have been suffering severe bladder and vaginal pain since I have had Lyme. Using the restroom it feels like I have an open sore. The pain makes me double over and brings me to tears. I know I need to see a specialist. We have discussed this and I know many others who suffer with it also.

Unknown said...

Interesting,

What about IND results in significant bands. Say you had band 41 as ++ and bands 31,39 and 93 asIND accross IGG and IGM?

LYMEMJ said...

Also read about the lab that say they DETECT THE ANTIGEN OF THE BORRELIA? the links are:
•Central Florida Research, Inc http://centralfloridaresearch.com/lab2/
Lyme Antigen Test http://centralfloridaresearch.com/lab2/index.php?option=com_content&view=article&id=50&Itemid=58
Copy and paste them in a new window, here the links are hard to get!

MJ said...

Can you please repeat this to the eight Doctors I've seen? "Remember-Lyme is a clinical diagnosis. Lab data is only supportive of the diagnosis"...?
I asked for my medical histories and none of the 8 physicians wrote the 21 symptoms I said I had; maybe that's why they didn't diagnose me with the Lyme?
You Montgomery Doctor were like the opposite, maybe you got the clinical diagnose first because you are "trained" to see it? or is it because you do not deny the existence of the tick borne disease? ? or does this other thousand of Doctors who misdiagnose Lyme is because they never studied about Lyme? Doctors of the US have not heard about the number one tick borne disease of this country? They do not make clinical diagnoses plus they do not order the labs at least to get information.... what a bad circle!

Cici said...

Is there a signifigance if there are is only 1 positive bands positive on the IgG however more on the IgM? Would that infleunce the Dr.s 'art' of diagnosing lyme?
And if there is IND on IgG for 31,39, & 93 should the test be repeated?

jmankoff said...
This comment has been removed by the author.
jmankoff said...

What can the 41k band indicate if not lyme? What other infections have flagella that might cause it to light up?

SaaaLaaaaa said...

I am being denied treatment by my doctor because I don't have a "positive" test. He claims it is an issue of insurance coverage, which I assume means that the test must be positive using CDC guidelines. I've had two Western Blots, both positive on bands 41 & 23, and a positive C6 ELISA in addition to ongoing symptoms a year after the tick bite. Is my doctor being truthful about the insurance coverage? You seem to imply that it is somewhat at the doctor's discretion whether or not to call a test positive or not. Thank you for any light you can shed.

Red said...

I have an appointment at a well known and respected teaching hospital in the infectious disease department, that my doctor referred me too, because I only showed band 41 on the blot. My doctor told me he could not give me anymore antibiotics until the appointment because it would falsely effect the tests they would conduct. I told him I am on crutches and cannot even hold a normal discussion when I am off antibiotics. I found another doctor who gave me 20 more days of antibiotics and now I am off the crutches again. I had a bullseyes rash and all of the symptoms of a tick born disease. I do not know what to do. My appointment is in 7 weeks. Should I stay on 20 days of antibiotics and than stop and that would give me three to four weeks before the appointment, or do I get off of antibiotics now and loose my mind again and ability to walk so that I can get an accurate test. I need help with this choice, please respond. Thanks

Unknown said...

I just want to thank you for this blog and your sharing of knowledge. Happ holidays!

Unknown said...

I had a Septoplasty + right Turbinate reduction on Tuesaday. I have been sick for a while with varying symptoms. Some days I feel fine. Some days I tired and aching. Some days I struggle pulling myself out of bed; exhausted and writhing in pain.

There are chains of lymph nodes swollen on both sides of my neck. There are also swollen lymp nodes in my armpits and groin area. My Doctors had one of the nodes behind my right ear removed and tested (biopsy) which was negative for "Cell Colonization"... So no cancer.

He ordered a battery of blood work consisting of 26 tests. I haven't been back to see my doc yet but my surgeon (ENT) had my results back yesterday. He told me that it came back positive for Lyme and to follow up with my doctor.

The anesthesiologist came in a few minutes later to ask some questions. She asked me if I am aware of any illnesses that I may have. I relayed to her that my ENT just told me that I have Lyme disease. She then told me that only one of the tests was positive but that the antibody test was negative, that it probably isn't lyme disease, and that Lyme is difficult to diagnose.

Not sure what to think but I'm seeing my Primary care today at 3:30pm. As a side note; I have been back in Northern NY now for almost 2 years (2 years in November) but have been bitten many times by ticks in the preceding 3 years in VA.

Unknown said...

Update:

Just saw my primary care physician.Not sure what the anesthesiologist was talking about but my doc confirmed the diagnosis: ELISA and Western Blot results = positive. Prescribe 3 weeks of Doxycycline 2 a day taken orally... We'll see how that works out.

Unknown said...

I just got the results back from my test - I have had problems with extreme fatigue, muscle aches and weakness, migraines that have gotten progressively worse since my teenage years. Took 20 years to be diagnosed with Fibromyalgia, no one ever did the test for Lyme disease, but now this one shows that

LYME 39 KD IGM Present
LYNE 41 KD IGG Present

But LYME IGG WESTERN BLOT INTERP & LYME ANTIBODY IGM, WESTERN BLOT are both negative. My doctor says this means I do not have Lyme disease and don't need to worry about it. I was bit by a tick when I was 13 - thinking back that's about when I started having a lot of my problems, though milder then. Should I seek a 2nd opinion?