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147426 tn?1317265632

Oligoclonal Bands - MAJOR RETRACTION!

Okay, everyone, this is it.  This is my major boo-boo of the year!  I have been doing a lot of reading on O-bands.  One of the big questions is whether you can diagnose MS with an LP that is negative for O-bands.  The answer is not what I have been telling people.  It goes more like this:  If the lab is using the newest technique for identifying O-bands, a technique that was reported to the world just 2 or 3 years ago, and if the technician is well-trained in the interpretation, then O-Bands should be positive in the great majority of patients at diagnosis.  The studies looking at the predictive value of "Positive oligoclonal bands" in CIS, show that about 96% of people at presentation will be positive for O-bands in their lumbar puncture.

So about 1 in 25 people will be negative if the right test is run and is run right!  Does that mean what we have heard here so many times, that a doctor "can't" diagnose MS if there are no O-Bands?  No, it does not.  I have a couple opinions on this topic, as always.

1) The doctor who isn't willing to take the time to find 1 in 25 is going for the easy points.  A neurologist is paid big-bucks and should be willing to stay with the atypical patient, keeping their mind open.  Not doing this is lazy.

2) There is STILL no recommendation in the world of MS Diagnosis that a positive LP for O-bands should be included in the requirements for diagnosis.

3) No neurologist is accurate in saying that no O-bands "rules out MS."

4) I am concerned that we don't know if all the labs that do the analysis for O-bands are using the new technique, called "Isoelectric Focusing with Immunoblotting."  or something similar.  We know that the minimum MRI strength recommended for MS diagnosis is 1T, yet some people are still being sent to MRI machines which are weaker.

So, I have to temper my statements about how accurate O-band testing is, keeping in mind the technique that achieves this 96% is relatively new.  But, IT IS NOT 100% as some doctors claim.

************************************************************************************************

OLIGOCLONAL BANDS - What Are They and How Are They Reported?

What Are O-bands?

Oligoclonal Bands are large groups of antibodies that can sometimes be found in the blood and in the cerebrospinal fluid, the CSF.  They are caused by a state of inflammation in either the body or the Central Nervous System or both.  This kind of inflammation is caused by the immune system which makes a colony of B-lymphocytes, by "cloning" one B-lymphocyte into a large group of cells.  All of these cells make the same antibody.  Because of this, the group of antibodies identified as an O-bands is huge.   The antibody may be directed against many things such as an invader like a virus or bacteria or against an abnormal cell, like a cancer or foreign cell like a transplant.  Or, for some some reason, the antibody may be directed against a tissue of the body itself.  This causes a condition referred to a "auto-immunity."  This word means "immunity to self."  

A few definitions:

The term "oligoclonal" means "oligo = few" and "clonal = produced by cloning."

The word "Band" refers to the appearance of these antibodies when a specific test is run on the fluid looking for them.

The immune system is programmed to ignore proteins and tissues of it's own body for obvious reasons.  However, several things may trigger it to attack its own body.  Some of these triggers are understood and some are not.  These antibodies, which attack our own tissues, are the most obvious villains in what are called "auto-immune diseases."  The most commonly known examples of autoimmune diseases are Autoimmune Thyroid disease, Lupus, Rheumatoid Arthritis, Psoriasis and many, many others.  In Multiple Sclerosis we know that some antibodies attack the myelin sheath which insulates the nerves of the white matter of the brain and spinal cord.  What we don't know is exactly what triggers the attack by our own immune system on our own nerovus system.

How Do They Test For O-bands?

To understand how oligoclonal band can be important in the diagnosis of MS, you have to understand a little about how they are found and counted.  Antibodies are found in the body by drawing blood and testing it or by obtaining spinal fluid and testing it the same way.  The process involves tagging the antibodies with something that will make them visible and then letting them diffuse across an area of gel or across special paper. I will just call this the "gel."  There is more to this process, but this is not important right now.   Because the body makes millions of different antibodies, there are a lot to look at, and each antibody moves to a different place on the gel.  Normally, in the healthy person, with no big infections or immune inflammation, the antibodies migrate across the gel making a broad area of that looks all the same throughout.  It is said to appear homogeneous.  Please look at the following link to see a picture of a normal result.

(Please note that the results of #4 and #5 here have been reversed)

http://www.ii.bham.ac.uk/clinicalimmunology/Neuroimmunology/IEF.htm

If there are huge amounts of the same antibody present in the sample of fluid (serum or CSF) then there will be dense lines superimposed on and going across the gel at one or more locations.  Remember, this is because there are clones of antibody-producing cells, each making abnormally large amounts of just one antibody.  All of these antibodies will migrate to the same spot on the gel and will show up as a darker line or "band."  Two clones of B-cells will make two O-Bands because each colony makes a different antibody.  The more colonies of cells there are, the more O-bands will show up.

Quix
the final part will be on the next post
34 Responses
147426 tn?1317265632
How are the O-bands Counted and Reported?

The blood will show the effect of these colonies out in the body, like an autimmune disease that is outside of the brain.  The CSF may show one of two things.  It can "echo" the same O-bands made out in the body because these antibodies "leaked across" the blood-brain barrier.  This can especially happen in infections.  Or, the CSF can show different O-bands than the serum.  If an O-band appears only in the CSF and not out in the body (the serum of the blood) then we know that those colonies of B-cells are making antibodies ONLY in the Central Nervous System, as would happen in Multiple Sclerosis.

IMPORTANT - The serum and the spinal fluid both must be tested for the O-Band result to be valid.   It is not enough to look for them in the CSF alone, so there must be a blood draw on the same day as the lumbar puncture.  The two results will be compared to see if there are any O-bands that exist ONLY in the CSF, but not out in the body. On the lumbar puncture report the only thing that is usually reported are O-bands that do appear in the CSF but DO NOT appear in the blood/serum. (see below)

There are four possible combinations of results you can see when you compare the serum with the CSF.


#1    The serum gel appears homogeneous with no dark bands

       The CSF gel appears homogeneous with no dark bands

INTERPRETATION:  This means that there is no source of cloned antibodies making large amounts of the same antibody in either the body or the central nervous sytem.  
This will be reported as "Negative" for O-bands on the LP report.


#2     The serum gel has dark bands across it (+ O-bands)

         The CSF has appears homogeneous with no dark bands

INTERPRETATION:  This means that any antibody clones are only out in the body and are not involving the central nervous system.  This will be reported as "Negative" on the LP result.


#3      The serum appears homogeneous with no dark bands

          The CSF gel has dark bands running across it (+ O-bands)

INTERPRETATION:  This result means that all of the O-bands seen in the CSF are unique.  If there are two or more O-bands on the CSF gel, then this would be reported as a "Positive" result for the O-bands on the LP report.


#4     The serum gel has dark bands (+ O-bands)

         The CSF gel also has dark bands (+ O-bands)

This means that there are some large groups of antibodies appearing in both places.  The two sets of bands must be carefully compared to see if all the bands are in identical locations.  If all the bands are identical it indicates that all source of the problem is out in the body and maybe also in the brain or the antibodies have leaked into the spinal fluid.  This will appear as a "Negative" result on the LP report and is is not consistent with Multiple Sclerosis.  However, if there are 2 or more bands which appear in the CSF, but do not appear in the serum,  this is likely to indicate MS.  This will be reported as a "Positive" result  for O-bands on the LP report.

Labs report O-bands differently.  Some report the number of distinct bands appearing only in the CSF.  Some just report Positive or Negative.  Also, the appearance of only one band is considered "equivocal" or "indeterminant."  One unique band in the CSF can be seen in normal people or in people with a CNS infection.

Quix
147426 tn?1317265632
The last part will be the meaning of O-Bands for the patient, for the diagnosis, for the prognosis, for whatever I can find.  It is not written yet.  Q
Avatar universal
I am not sure what test I had run, but will definitely look into it.  I did test negative for O-bands, but had an elevated IgG Index.  I also have brain lesions only.  What can cause these other than MS?  Am I barking up the wrong tree here??????
147426 tn?1317265632
If you read the top part, the negative O-bands are found in 1 out of 25 patients with MS at diagnosis.  So, it does not rule out MS, it just makes it less likely than I have been saying.

My next blurb will talk about the other stuff.

Quix
382218 tn?1341181487
My LP was negative for O-bands and elevated IgG index.  I asked my neuro about this last week because it had never been explained to me, and he said without going into a lot of detail something to the effect that it probably was an inaccurate result due to the testing method.  I didn't bother to probe further since my dx is confirmed based on several other criteria, and I had too many other questions on my list for him to spend more time on this item.  It did make me curious though; if they don't trust the accuracy of the way that they test, why bother?  

db
147426 tn?1317265632
Very interesting.  Perhaps he has requested the updated test and it hasn't happened.  Why do it?  Because if it is positive, you have good info.  If it is negative, you have the option of disregarding it.  And it is part of the protocol.

Actually, you're right, but as we have seen the world isn't rational.

What you tell me tho, is every lab has NOT switched over to the better test.  That makes me wonder if all the neuro's that claim "no O-bandsm no MS" know what test their lab is using.

What do you think?

Quix
Avatar universal
Qix, thanks for this clarification. I don't think we knew here that there are now more accurate CSF analysis prodecures out there. If this info and clarification hasn't found its way to the Health Pages, it really should.

Also, everyone needs to remember that many cases of MS have been diagnosed with no LP at all, but based on other evidence. So although an LP is often ordered, it isn't some requirement.

ess
Avatar universal
My wife had no o-banding and her IGg index was not elevated, but was diagnosed and starts beta-seron next week.

Just an example.

Quix, great write up...thanks for the info.
428506 tn?1296557399
Wow, this is very informative!

I have a q, and apologize if it's answer is contained in your posts, but if it is I missed it.

Does it matter when you get testing for O-bands?  What I mean is, if my symptoms go away, should I still get this test?  I've heard claims going both ways on this one, so I'm a bit confused.  I (or anyone) would not want to get this invasive test done unless I am sure it is done at the right time (if time is even a factor).  

Also, what about medication?  If I am on steroids, could that effect the test results?

Thanks so much in advance!

428506 tn?1296557399
Sorry, thought of another Q about all of this.

I get confused over "having ms" vs. "probably will develop ms" descriptions.  It seems some tests will only show positive over time, and that time varies by individual, but ppl can have lots of symptoms before knowing for sure.

Do you think CSF analysis is a good test for ppl who have only been symptomatic for a relatively short time?  If this test is neg, but symptoms persist/recur, should it be repeated?  

People can stop reading at this point, below is just my rant about why I have these Q's!  Read at own risk of being bored :-)

I had a clear MRI in Feb. after my first episode that began Jan. After a month of normalcy, I had a second "episode" in April that is still affecting me.  My 1st neuro ordered an LP at my request, but bullied me into not going through with it, saying I was wasting everyone's time since my MRI (brain, c-spine, w and wo con.) was clear.  He said I needed Prozac.  I consulted 2 therapists.  Neither felt I was depressed or that my symptoms could be purely anxiety based.  Neither recommended medication or that I continue therapy, both said I need  a new neruo.  Went to my doctor, she said there were no more tests for her to do and said I really need a new neuro (she had already checked my blood and hear, all checked out).  I go to see a new neuro this Thurs, so this post came in perfect time for me!  But obviously, I am scared I will be dismissed again, so I want to go in armed with information.

Thanks again!
198419 tn?1360242356
HAVE I TOLD YOU LATELY HOW WONDERFUL YOU ARE! WELL, YOU ARE!

THIS IS GREAT.  CAN YOU ADD IT TO THE HEALTH PAGES.  WE GET SO MANY QUESTIONS ABOUT THE 0-BANDS.  YOU DON'T EVEN HAVE TO WAIT UNTIL YOU GET YOUR LAST PART IN, YOU CAN DISCLAIMER IT AS WORK IN PROGRESS. . .

THANK YOU SO MUCH FOR THIS, IT'S SO HELPFUL AND INFORMATIVE.

SL
279234 tn?1363105249
Thanks for the info..there is a lot of  neurologist, though, that try to throw out MS as a DX if the LP doesn't show o-banding which I think is wrong to do for the same reason you stated above. Especially when all labs are probably NOT doing things the new way. The funny thing is, you mentioned how protocol isn't followed all the time including the strength of the MRI machine. My last neuro didn't follow protocol because he kept sending me to a 0.7 tesla strength machine and it makes you wonder what else wasn't done right including the new standards for doing the LP, which mine was negative.

By the way, how would you go about finding out if they used the new or old method of doing the LP?
233622 tn?1279334905
If you have not had an LP should you?  I was dx'd without one due to other MS symptoms.

I was very happy NOT to have one.  But then if an neg LP does not rule out MS then I am wondering why go through it.

LA
373367 tn?1246402035
Thank you for taking the time to organize and write all of this down for us.  I know this is all a "labor of love" for you, but we all appreciate you SO MUCH!!

I was wondering if it is possible for more O-banding in the CSF vs serum to occur in ANY other diseases or is it unique to MS?  

thanks,
Stacey  
147426 tn?1317265632
Wow!  It seems that my info on the new technique for determining O-bands was the most exciting part of my post.  That is very interesting.  I think we all suspect that the technique is not necessarily in broad use.

But, I also really need input on the understandability and readability of the part that describes how they test for O-bands.  Is it in good enough shape to just place up on the Health Pages?

Now: There were some great questions asked whose answers are for the next segment, but I'll go through them briefly first.

Sherry - Brain lesion, and an elevated IgG Index, along with suggestive symptoms and signs does suggest MS.  In the McDonald Criteria the O-bands and the IgG Index are interchangeable piece of information.

ess - You make a huge important point.  An LP is not a required part of the qork up for MS.  Many people are rightly diagnosed with having one.  So if it is not needed all the time, how in the heck can a neuro rule out MS if it is negative?????

Magoo - Great to see you back!  Yes, your wife was diagnosed (as we thought she would be) AND WITHOUT AN LP AT ALL!  Thet's the point I'm making.

Wonk - The O-bands seem to appear with successive bouts of inflammation.  There are fewer O-bands (in general) earlier in the disease.  As you acquire more you keep them life long.  If someone is in remission, their O-band count will be the same.  Steroids will not change this.  Your other questions we should deal with on a thread devoted to them, not this one, so if you would post your dilemma in a new thread.

Slightly - The lab test report ideally will state the method they used to run it.  If it doesn't, most lab results carry the name of the lab and the pnone number.  You can call the lab supervisor and ask what specific test is used to detect O-bands.

LA - The LP is needed as a supportive test when there is not enough information from the history and physical (to which too little attention is paid!) and from the MRI evidence.  It's role is supportive.  It is not supposed to be used as a rule-in or rule-out test!!!!!!!!!!!!!

I'm glad you had these questions.  I willtry to clear up these and any more I can think of plus any that more people come up with.

Again:  Was the part on How O-bands are tested for and interpreted clear enough to go ahead and put up??

Quix, quizzically???
476834 tn?1228398709
I'm confused,

why is my neurologist suggesting I get an LP?  when she says most likely it is ms?  OHHHHHH ugggg,, I'm just not understanding????  

So an LP can NOT rule in or out Ms right?

geeeeese Quix i'm so confused and dont know what to do:(
147426 tn?1317265632
If the neurologist is looking for more evidence pointing toward MS they will request an LP.  You can't rule MS in or out SOLELY ON THE BASIS OF THE LP.  But it certainly can act as supporting evidence.  Does this make sense?

Quix
147426 tn?1317265632
I meant to add that all of the evidence, symptoms, signs, MRI, LP, VEP are looked at together.  The only part that can make the diagnosis ALONE is the history and physical over time.

I'm trying to get a diagnostic page up soon on the Health Pages.

Quix
Avatar universal
The article seems quite clear . . . so clear, it gave us all something new to ponder :0

Thank you for all you do.

Sherry
198419 tn?1360242356
You Question: Was the part on How O-bands are tested for and interpreted clear enough to go ahead and put up??

Yes, it's good to go up.  You've got: definition of O-Bands, various testing techniques, possible outcomes (ref: band or no bands) anything additional to that, is just icing!

I will read it again for flow and order, but I think it's good.  I'm thinking you can put the possible outcome examples in table form (your #1 - 4's), that way it would break up the text a little.  It's super!

Thank you again, Mama Q,
-SL

147426 tn?1317265632
Uhhh....table form???????

This is where I show I'm a technotard.

Would you do it and give me an example?  :)

Quix
198419 tn?1360242356
Ok -

I put the possible outcomes in a table - where can I send it so you can see it?

Can only post things as text here.

-shelly
198419 tn?1360242356
I can save it as an image and post it on my pictures or something, but I won't be able to view it from the computer I'm at.  We're blocked from about everything here.

-Shell
198419 tn?1360242356
Oh boy, your going to have to knit me a beating, I didn't think that would post like that on the health pages - was playing around to see if it would allow the table - yikes. . .
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