This was a major theme in the article highlighting that you need to avoid testing in low-probability situations. Therefore, if you test all MS patients because MS is 50 times more positive, you may get some false positive results. This is important because we know that MS is about 50 times more common, at least in our region of the world, than MOGAD. Previously we did a study from our laboratory, and what we found was that the rate of false positives or positives in other diseases was reasonably high with the low titer results, so up to half of those patients had an alternative diagnosis. Well, once you got up to the high positive, almost all of these patients had MOG antibody disease. What we suggest is we avoid testing in low-probability situations, so if you have a patient where everything looks extremely classic for multiple sclerosis, we don't recommend testing the MOG antibody because you might run into low positive results that can confuse the picture. While with the high positives, they're very reliable across all the laboratories. When you test MOG antibodies across multiple laboratories, there's pretty poor agreement for low positivity, so it's not as robust in that in one lab, it might be low positive, in another lab, it might be negative. Up to 1%-2% of MS patients, for example, can have MOG antibodies and indeed, they looked at a hospitalized group of patients and found that 1%-2% of those patients could have low positive MOG antibodies. When do we order the MOG antibody and how do we interpret it? Well, one of the issues with the MOG antibody that we don't really see with the aquaporin-4 antibody is that at low titer, sometimes we can see some slight binding in disease controls. When to order MOG-IgG and how to interpret 4-7 In our laboratory, a cutoff of 100 or greater is considered a clear positive or high positive, and a cutoff of 20 or 40 is considered a low positive. As I said, we use the flow cytometry and there are different cutoffs here. So either of these are appropriate tests to test for MOG antibodies. The one we use here at Mayo Clinic is the live cell-based assay, which does confer some slight advantage over the fixed cell-based assay in terms of sensitivity and specificity, but we really recommend cell-based assays. There are two types of cell-based assays. The MOG antibody assay methodology was included in the diagnostic criteria, and this is mentioned here. MOG-IgG assay methodology and reporting 1-3 So, you can have an antibody titer anywhere from 20 to 10,000. Then what we can do after that, is we can do an endpoint titer, where we will assess and dilute each sample at different dilutions to give us the strength of positivity, and in our laboratory, we start at 20 and then we go to 40, 100, 1,000, 10,000. Other laboratories might use an immunofluorescence technique to look at the antibody, where they look under the microscope for binding to the cell surface. In our laboratory, we use a flow cytometry called a FACS assay, and we're able to get a readout of the strength of positivity with that. Then, if you do have MOG binding, you have a secondary antibody that binds to the FC portion of the MOG antibody and helps you get a readout of how much positivity you have. We have a patient serum and we run it in our laboratory, and we look for binding to MOG on the surface of these cells versus not binding to cells that don't have MOG on the surface. When we think about the MOG antibody assay methodology, if we just look here, this is done by what we call a cell-based assay. This was a study led by Brenda Banwell and many of us were involved, and this is the international MOGAD panel proposed diagnostic criteria. This is focusing on a study that was recently published in the Lancet Neurology in early 2023. And today we're going to focus on the third well-defined disease, which is this myelin oligodendrocyte glycoprotein antibody-associated disorder or disease (MOGAD). We have aquaporin-4 antibody positive neuromyelitis optica spectrum disorder, which was the first antibody discovered as a biomarker of CNS demyelination. We have multiple sclerosis (MS), which ranges from radiologically isolated syndrome all the way to secondary progressive MS. When we think about inflammatory diseases of the central nervous system associated with demyelination, then there are three major ones that we can think about. Distinct inflammatory diseases of the CNS associated with demyelination These are my disclosures here, which are not too relevant to this talk, which will focus mostly on diagnosis. Today I'm going to talk about MOG antibody-associated disease (MOGAD) and in particular about the recent diagnostic criteria. I work in the Neuroimmunology Laboratory at the Mayo Clinic and the autoimmune neurology and multiple sclerosis clinics.
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