June 25

MOGAD Titres Explained

Important Information

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

I would like to thank Dr John Chen from the Mayo Clinic and The MOG Project for reviewing this post. It would not be possible without them. 

What is a titre level?

You may have seen these strange ratios before which look like this - 1:100

An antibody titre is a type of blood test that determines the presence and level (titre) of antibodies in the blood. This test is carried out to investigate if there is an immune reaction triggered by foreign invaders (antigens) in the body1.  In the case of MOG Antibody Disease (MOGAD), are there antibodies in the blood which are attacking the myelin in the central nervous system?

An antibody titre is generally presented as a ratio at the highest dilution where the antibodies remain positive, after the blood has been diluted with a solution such as saline.

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

In MOG Antibody Disease these titres are used to show how 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, while other assays, such as ELISA are not reliable 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. Either blood of a patient or cerebrospinal fluid can be tested for MOG antibodies.

The titre amounts I will talk about in this video 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 a true MOGAD result, while there are more false positives at lower titre levels2. A higher titre level is one where the second number in the ratio is higher.

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 of had true MOGAD, whilst majority of the 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 make sure that everything fits the diagnosis as some countries do not report titre levels but rather a positive or negative result. In addition, there are many patients with true MOGAD who 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 further clinical events, but more recent data indicate that patients might remain positive for many years and not relapse, and even patients who become negative could still relapse (becoming positive at time of relapse). Antibody titres, even when measured longitudinally, did not clearly correlate with disability outcomes3.

Most studies reported that a relapsing disease course was more likely in patients with higher MOG titre levels at onset and those who test positive for MOG antibodies repeatedly over time, whereas low titre MOG titre levels were more likely with a monophasic disease course4.

However researchers are still unsure about this as this area of research needs more studying5!

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 more likely to relapse than those who do not5. Those with very high titres might be more likely to have persistent MOG and therefore may be a bit more likely to develop a relapse, but this remains unclear5.

A very high titre level is equal or greater to 1:1000 and 1:10000, (according to the Mayo FACS MOG assay) but 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 define MOGAD case?

Studies have found that some patients who have Multiple Sclerosis (MS), and also healthy patients can also have a very low level of MOG antibodies5. This 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 most of the false positives. However, a few false positives were also found at the 1:100 level5.

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

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

A positive MOG test by itself 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 about 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 which can result in a negative result too. In a recent MOG Project Livestream about antibodies lasting for 6 months so MOG antibody positivity by itself would not necessarily be suitable to diagnose someone with MOGAD5.

In my own case, my neurologist said that he believed that I had MOG Antibody Disease whilst 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.

It was only after I received the result of the blood test which was positive for MOG antibodies where my diagnosis changed from Transverse Myelitis to MOGAD.

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

Any form of immunotherapy could potentially influence titre levels but it is thought that plasma exchange is likely to effect it the most. IVIG may also possibly influence titres along with Rituximab and 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. Whilst there have been some diet studies in related conditions such as Multiple Sclerosis (MS) and NMOSD this not been studied yet in MOG Antibody Disease.

References

1.          Sinha Dutta S. What is an Antibody Titer? News Medical. https://www.news-medical.net/health/What-is-an-Antibody-Titer.aspx. Published 2021. Accessed March 30, 2022.

2.          The MOG Project. MOG-AD DIAGNOSIS: TESTING AND TITERS. The MOG Project. https://mogproject.org/2021/10/mogad-diagnosis-testing-and-titers/?mc_cid=2591340e04&mc_eid=c6b8ce58e8. Published 2021. Accessed March 30, 2022.

3.          Marignier R, Hacohen Y, Cobo-Calvo A, et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021;20(9):762-772. doi:10.1016/S1474-4422(21)00218-0

4.          Hegen H, Reindl M. Recent developments in MOG-IgG associated neurological disorders. Ther Adv Neurol Disord. 2020;13(1-20):259-261. doi:10.1177/

5.          The MOG Project. MOG AD Diagnosis: Testing and Titers.; 2021. www.youtube.com/watch?v=8-MDEOd_08Q.

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About the author 

Scott Tarpey

Scott was diagnosed with Transverse Myelitis (TM) in March 2020 caused by MOG Antibody Disease (MOGAD). He founded MyMyelitis in July 2020 to raise awareness of TM, MOGAD and similar neurological conditions to help others with their recovery.