Research: antibody production and cortical lesions

Epub ahead of printCalabrese et al. The association of intrathecal immunoglobulin synthesis and cortical lesions predicts disease activity in clinically isolated syndrome and early relapsing-remitting multiple sclerosis. Mult Scler. 2011 Aug 25.

Background: The production of immunoglobulin by B cells and plasma cells within the brain and spical cord is a major biological feature of MS. Studies have suggested a primary role of the B cell and immunoglobulin response in causing irreversible brain damage. 

Objective: To evaluate whether, in the early phases of MS, immunoglobulin synthesis within the nervous system correlates with the presence of cortical lesions and if their association could predict the clinical course of MS. 
Methods: 86 patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included MRI and cerebrospinal fluid examination. 
Results: MS’ers with clinically isolated syndromes (CIS) having cortical lesions and nervous system synthesis of immunoglobulin had a 3.4x greater risk of conversion to MS; whereas CIS patients without cortical lesions and immunoglobulin had the lowest risk of conversion to MS (0.1X). 
Conclusion: The investigators observed that the association of nervous system immunoglobulin synthesis and cortical lesions was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity.
“This study supports pathological studies that B cell activity within the nervous system correlates with cortical disease or superficial gray matter pathology. Another reason to target B cells to try and prevent progressive gray matter pathology and hopefully prevent or delay the acquisition of cognitive dysfunction in MS.” 
Previous, related, posts of interest:

16 Aug 2011
Background: Inflammation of the coverings layers of the brain and spinal cord, in the form of lymph node like structures, has been suggested to play an important role in the development of grey matter pathology in MS. 
07 Jun 2011
Grey Matter (5) & B Cells: Baminercept in SPMS. The immune system forms and maintains the ectopic B-cell follicles in the brain & spinal cord by producing a cocktail of immune messengers called cytokines. One of these 
08 Jun 2011
This study is also targeting the B cell within the central nervous system (CNS) in the hope of disrupting the ectopic B cell follicles and thereby trying to stop progressive cortical or grey matter disease progression. Rituximab is a 
06 Jun 2011
Grey matter (4) – Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Magliozzi et al. Brain. 2007 Apr;130(Pt 4):1089-104. In MS the 

05 Jun 2011
Methods: In this study specialist MS pathologists analysed global brain involvement in MS focusing on the normal-appearing white matter (NAWM) and the cortex (grey matter). Findings: (1) New and active focal inflammatory 
05 Jun 2011
“This and other studies show that grey matter involvement is there from the start. I use this as argument for aggressive early treatment. It is better to protect the brain, particularly the grey matter, than to compensate for the 
05 Jun 2011
In this study the investigators were able to relate cortical or grey matter lesions and tissue loss or atrophy to cognitive impairment in patients with RRMS. “This study adds to the growing body of evidence that grey matter 
02 Jun 2011
“Grey matter pathology is an increasing important area of MS research and an important target for both DMTs and symptomatic therapies. I am sure that grey matter pathology is responsible for the cognitive issues PwMS 

4 thoughts on “Research: antibody production and cortical lesions”

  1. Prof G,Many thanks. This is the sort of research that I am interested in and your helfpul comment. I think this is the USP of this blog – latest key research with helpful translation by an expert.Any idea when B cell depleting therapies might become available?The general intro to MS is very well covered by the national MS societies (and MSRC, MS Trust). It's the information on research / therapies which this blog should focus on.Looking forward to your feedback from the ECTRIMS/ACTRIMS conference.

  2. Re: "How much of all this would general neurologists know? Or need to know?"If they are in the business of looking after MS'ers they need to keep up-to-date with developments in the field. B cells are a hot topic and there is a lot happening in the field.

  3. Re: "Any idea when B cell depleting therapies might become available?"Depends on you definition of a B cell therapy; at present most of the licensed MS therapies have some effect on B cells. If you are waiting for the anti-CD20 monoclonal antibodies, you will have to wait another 5 years. The ocrelizumab Phase 3 trials are still recruting (RR and PPMS). There is some off-label use of Rituximab going on already; this is not common in the UK, but widespread in the US.

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