Is OCB negative MS a different disease?

Do you know your OCB result? If your are OCB-ve you are likely to do better. #MSBlog #MSResearch

"The study below shows that MSers without OCBs (oligoclonal immunoglobulin bands) in the spinal fluid have less brain atrophy (end-organ damage) than MSers with OCBs. This data supports the findings of our meta-analysis that showed that OCB-ve MS has a better prognosis than OCB+ve MS. Am I surprised? No I am not. I have always maintained that when we find the cause of MS and change our definition of the disease, that OCB-ve MS will turn-out to be a different disease. A lot of people don't agree with me on this. The answer lies in the philosophy of how define a disease. In medicine, but not psychiatry, we typically define a disease as a clinico-pathological correlate; i.e. a certain clinical presentation (dissemination in time and space in white matter tracts, with or without evidence of conduction slowing on evoked potentials) in the presence of characteristic pathology (MRI lesions, CSF OCBs or biopsy) defines MS."

"The problem in MS is that we can't do biopsies in everyone to make a diagnosis of MS so we rely on MRI and spinal fluid studies. Spinal fluid is a liquid biopsy and is the closet we can get to the pathological process in MS. The presence of OCBs in the spinal fluid that are produced within the central nervous system tells us that there is a specific B-cell response occurring within the brain and spinal cord. These B cells must be responding to something. Why do I say this? The list of conditions associated with spinal fluid OCBs is relatively small. OCBs are typically found CNS infections and rare paraneoplastic syndromes and other putative autoimmune diseases; diseases in which we have a pretty good idea of the antigens driving the disease. This is why we need to find out what the OCBs in MS are responding to; this is likely to be key to finding the cause of MS."

"The diseases referred to above that are associated with OCBs are usually easy to differentiate from MS, which is why spinal OCBs in the correct clinical setting is very characteristic of MS. What is interesting is that MSers who fulfill the diagnostic criteria for having MS differ in their clinical course based on whether or not they have OCBs. What this is telling me is that the pathology underlying OCB-ve MS is different to that that what is present in OCB+ve MS and the study below corroborates this finding. It would be interesting to know if OCB-ve and OCB+ve MS also differ in their response rates to DMTs. I would predict that OCB-ve MS is less likely to respond to anti-B cells therapies such as rituximab or ocrelizumab. Please note this is a hypothesis."

"These findings argue for a renaissance in spinal fluid sampling. Since MRI has entered clinical practice the number of lumbar punctures done to diagnose MS has plummeted. I think these data suggest we should relook at this practice. Why? We only have one opportunity to get the diagnosis of MS correct and that is early in the course of the disease in the so called diagnostic phase. A lumbar puncture helps exclude MS mimics and provides prognostic information that may affect decision making around DMTs. It may also allow us to include this information in our registers so that we can explore the course of OCB-ve and OCB+ve MS in more detail and assess whether or not they respond differently to DMTs."

"This post is very technical; if you don't understand it I am prepared to do a short google hangout to explain it further. Please let me know if it does not make sense."

"In conclusion and to stop me rambling on about a topic close to my heart, I can't stress how important the issue of OCBs is to the field of MS."



Ferreiraa et al.  Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy. Journal of Neuroimmunology, online 26 June 2014.

Background: To investigate whether MSers with and without CSF oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. 

Methods: 28 OCB-negative and 35 OCB-positive MSers were included. 

Results: Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. 

Conclusions: OCB-negative MSers, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS may represent a clinically relevant MS subgroup.

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