Thursday, 20 September 2012

Research: Antigen Targets in Early MS


Limited information is available on the identity of antigens targeted by antibodies present in cerebrospinal fluid (CSF) of patients with Clinically Isolated Syndrome (CIS). The aim of this study was to identify novel antigens for CIS and investigate their prognostic potential to predict conversion to Multiple Sclerosis (MS). We applied Serological Antigen Selection (SAS) to identify antigens interacting with antibodies present in the pooled CSF from 4 CIS patients, who developed MS. Antibody reactivity towards CIS antigens identified by SAS was tested in CSF and serum from patients with CIS (n=123/n=108), MS (n=65/n=44) and other (inflammatory) neurological diseases (n=75/n=38) as well as in healthy control sera (n=44). Using SAS, a panel of 6 novel CIS candidate antigens was identified. CSF antibody reactivity was detected in both CIS and Relapsing-Remitting (RR) MS. Serum reactivity was significantly increased in CIS and RR-MS as compared to controls (p=0.03). For 2 antigens, the frequency of antibody positive patients was higher in CIS patients who converted to MS as compared to CIS patients without conversion. We identified novel CIS antigens to which antibody reactivity was primarily detected in CIS and RR-MS as compared to controls. Possible prognostic potential could be demonstrated for 2 antigens

This study made a expression library which means you make take the activated genes from the tissues and use bacteri to express the proteins that would be made, of proteins from chronic MS lesions and normal appearing white matter. They then looked at antibodies from 4 people with clinicall ioslated syndrome who then went on to get MS and saw what the antibodies reacted to. We got some new target molecules on was Host cell factor 1 regulator 1 which controls the movement of host cell factor 1 in the cell and this controls transcription of Herpes virus among other things. Others may be against other targets like bestrophin 1. reactivity to these were present in CIS and RRMSers. Is this causal or a response to tissue damage?  I think it shows further that MSers can react to a lot of diffeent things in the brain and I know that some of these antibody responses will not be good for you. 

4 comments:

  1. How can you decide what is a CIS anyway? Unless someone has never had any symptoms and then goes on to have an event that worries them and goes to the doctor and he thinks it might be a CIS, then you can define it. How many MSers begin with a bit of tingling, a need to go to the loo more often, a bit of a weakness in one foot, that they ignore or explain away, which might've been their CIS

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  2. You have a fair point but their are clearly neurological symptoms that do make people go to the docs, the obvious one is optic neuritis...if your vision goes you know it is not right and seek medical advice pretty quickly.

    As such there are some early signs suggestive of MS that makes one suspect MS and so we are indeed able to do trials on CIS to see if people convert to MS.

    Indeed Team G and firends have a neuroprotective trial in CIS ongoing as we speak. I hope we can recruit quick enough because there is a small time window between the CIS event and the need to start treatment and so the prospective recruitee with have little time to find out what MS is before decided and if they take too long they will not be eligable

    It would be interesting to know how may CISers start seeking information on MS and read blogs like this, or does visiting blog sites such as this only get frequented by MSers friends & family (& pharma, doctors and researchers etc.)

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  3. I am a CISer. I went to the docs with tingling in my foot and a loss of sensation in my toe. Most people in my circumstances wouldn't have gone to the docs but something just felt wrong. He brushed it off but I insisted on a referral to a neuro as it had become left sided tingling (very mild) but because it (at that point) was all one-sided. The neuro also was quite dismisssive but agreed to an MRI just as belt and braces. Low and behold, I had a small number of periventricular lesions and a diagnosis of CIS. I also know that lesions plus symptoms equates to an almost inevitable conversion to MS in the long run (c.80-90% according to various studies). I therefore don't really think of myself as being very different to those with diagnosed MS in terms of uncertainty about the future; albeit I'm very grateful to not suffer any disability at present. It hit me incredibly hard. My hope is based around research which suggests newly diagnosed CISers (when accounting for both those who end up 'benign' and those who don't convert or only convert radiologically) have a c. 50% chance of a relatively mild condition at the 20 year mark.

    Since my diagnosis I have been on this site multiple times a day, every day. I have found it utterly invaluable as both a source of up to date research and also interesting commentary. The time you and Prof G take to answer people's questions (often in the face of remarkably hostile posters who seem to blame their MS/lack of cure on you and Prof G personally!) is a kindness to people in my position that you must not underestimate. I can honestly say this site has been a major factor in helping me cope with what has been an extremely traumatic period.

    In terms of the CIS neuroprotective trial you mentioned, I would absolutely be interested in being recruited for this. How do I get details (I'm about 4 months post-CIS if that's not too late?)?

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    1. The trial is NCT01451593 on www.clinical trials.gov however it is for optic neuritis and you need to get enrolled within 4 weeks of symptom onset. It has a small time window to recruit but this is when we think the drug will be more active.

      However keep your eyes peeled for studies as you are golddust to pharma becuase if companies can show you can stop MS appearing then they are on to a winner. I believe this can happen.

      I will also ensure we do CIS posts.

      Thanks for your kind comments

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