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Can you Diagnose MS with an LP ...

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Can you Diagnose MS with an LP that is Negative for O-bands?


If the lab is using the newest technique for identifying oligoclonal bands (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 (Clinically Isolated Syndrome), 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 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 reason, the antibody may be directed against a tissue of the body itself. This causes a condition referred to as "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 nervous system. 


How do they Test for O-bands?


To understand how oligoclonal bands 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)


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.


How are the O-bands Counted and Reported?


The blood will show the effect of these colonies out in the body, like an autoimmune 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.


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








The serum gel appears homogeneous with no dark bands


CSF gel appears homogeneous with no dark bands


There is no source of cloned antibodies making large amounts of the same antibody in either the body (blood serum) or the central nervous system. This will be reported as "Negative" for O-bands on the LP report.











The serum gel has dark bands across it



CSF has appears homogeneous with no dark bands


This means that any antibody clones are only out in the body (blood serum) and are not involving the central nervous system. This will be reported as "Negative" on the LP report.









The serum appears homogeneous with no dark bands



The CSF gel has dark bands running across it


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.








The serum gel has dark bands




The CSF gel has dark bands

This means that there are some large groups of antibodies appearing in both places. The two sets of bands (serum and CSF) must be carefully compared to see if all the bands are in identical locations.



If all the bands in the CSF gel also appear in the serum, this means that the source of the inflammation is out in the body and the antibodies leaked over into the spinal fluid. This will appear as a "Negative" result on the LP report and 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.   There are antibodies being made only in the Central Nervous System.  This is consistent with MS.  This will be reported as a "Positive" result for O-bands on the LP report.

































Laboratory Reporting


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.



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