MOGAD Titres Explained

Important Information

Please be aware that this is an emerging area of research, and this could change in the future!

I want to thank Dr. John Chen from the Mayo Clinic and The MOG Project for reviewing this post.

What is a titre level?

You may have seen these strange ratios before, which look like this - 1:100
An antibody titre is a blood test determining antibodies' presence and level (titre) in the blood. This test investigates if an immune reaction has occurred due to foreign invaders (antigens) in the body¹. In the case of MOG Antibody Disease (MOGAD), are there antibodies in the blood attacking the myelin in the central nervous system?

An antibody titre is generally presented as a ratio. This ratio is at the highest dilution, where the blood remains positive after the blood has been diluted.

For example, a positive test at a ratio of 1:100 indicates that diluting one part of the blood sample to 100 elements of the diluent solution (saline) is positive. But weakening the blood further leads to an undetectable antibody level in the blood sample¹.

In MOG Antibody Disease, these titres show at what level of dilution leads to the MOG antibodies being undetectable.

How are MOGAD titre levels tested?

Cell-based assays should be used to test for the MOG antibody. In contrast, other assays, such as ELISA, are unreliable for detecting MOG antibodies². Cell-based assays can be live or inactivated, but live cell-based assays are reported as having a slightly higher specificity and sensitivity². MOG antibodies can be tested in a patient's blood or cerebrospinal fluid.

The titre amounts I will discuss in this post refer to the Mayo Clinic FACS assay, but this may be different for other MOG antibody assays used elsewhere.

What do MOG antibody titre levels mean?

Generally, a higher titre level is more likely to be an accurate MOGAD result. At the same time, there are more false positives at lower titre levels². The bigger the second number is in the ratio, the higher the titre level is. 

For example, 1:1000 is higher than 1:100, and 1:100 is higher than 1:40. A recent study found that all patients with a MOG antibody titre had true MOGAD, while most false positives were at the 1:20 – 1:40 titre levels and a few at the 1:100 level².

It's up to the physicians and neurologists to put it all together and ensure that everything fits the diagnosis. Some countries do not report titre levels but rather a positive or negative result. In addition, many patients with true MOGAD have low titre, while there will rarely be a patient with a high titre that is a false positive².

Do high MOG Antibody Disease titre levels mean a worse outcome?

Early studies suggested that high MOG antibody titres could predict other clinical events. Still, more recent data indicate that patients might remain positive for many years and not relapse. Even patients who become negative could relapse in the future (becoming positive at the time of relapse). Even when measured longitudinally, antibody titers did not correlate with disability outcomes³.

Most studies reported that a relapsing disease course was more likely in patients with higher MOG titre levels at the onset. A relapsing disease course was also likely in those who tested positive for MOG antibodies repeatedly over time. In contrast, low titre MOG titre levels were more likely with a monophasic disease course⁴.

However, researchers still need to figure out this as this area of research needs more studying!⁵

Do high MOGAD Titre Levels mean a patient is more likely to relapse?

Each person is different, but those who persistently test positive for MOG antibodies are likelier to relapse than those who do not⁵. Those with very high titres might be more likely to have persistent MOG and, therefore, maybe a bit more likely to develop a relapse, but this remains unclear⁵.

A very high titre level is equal to or greater than 1:1000 and 1:10000 (according to the Mayo FACS MOG assay). Still, it could be different for assays used elsewhere⁵. However, as discussed earlier, a persistent high MOG antibody titre does not guarantee that a patient will relapse. Those with a negative titre level can relapse, but this tends to be less likely⁵.

What titre level is likely to be a definite MOGAD case?

Studies have found that some patients with Multiple Sclerosis (MS) and healthy patients can also have very low MOG antibodies⁵. Testing positive for a low amount of MOG antibodies often leads to confusion about the diagnosis.

In patients with a high titre - 1:100 or 1:1000 or greater (according to the Mayo FACS MOG assay), the vast majority do have MOG Antibody Disease⁵.

Low-level titres - 1:20 & 1:40 (according to the Mayo FACS MOG assay) were where the study had the most false positives. However, the Mayo Clinic also found false positives at the 1:100 level⁵.

Sometimes assays do not report a titre level, so it is harder for patients to know if they get a positive or negative result.

Is a positive MOG antibody test the only thing needed for a MOGAD diagnosis?

A positive MOG test is not the only thing needed for a diagnosis. As mentioned earlier, patients with other conditions and healthy patients can also test positive for MOG antibodies⁵.

It is up to the physicians to put together everything and make sure everything fits the diagnosis. False positives can happen, especially when combined with treatments such as plasma exchange, where antibodies are removed from the body⁵.

Antibodies can also go away over time and diminish, resulting in a negative result. A recent MOG Project Livestream mentioned antibodies lasting for six months, so MOG antibody positivity alone would not necessarily be suitable to diagnose someone with MOGAD⁵.

In my case, my neurologist said that he believed that I had MOG Antibody Disease while recovering from my Transverse Myelitis attack. However, before I could be diagnosed with MOGAD, he needed to test my blood and spinal fluid for MOG antibodies to complete the diagnosis.

After receiving the blood test result, which was positive for MOG antibodies, my diagnosis changed from Transverse Myelitis to MOGAD.

Can treatments reduce MOG antibodies, and if so, by how much?

Any form of immunotherapy could influence titre levels. Still, plasma exchange is likely to affect it the most. IVIG may also possibly influence titres along with Rituximab and Azathioprine (Imuran), but to what degree is hard to tell⁵.

Are there any ways to reduce MOG antibodies outside of treatments?

Currently, researchers are unsure if any diet, vitamins, or supplements could reduce MOG antibodies. While there have been some diet studies in related conditions such as Multiple Sclerosis (MS) and NMOSD, this has not been studied yet in MOG Antibody Disease.