Saturday, 28 November 2015

PoliticalSpeak: are you an early adopter?

Please adopt our policy and pledge your support. #PoliticalSpeak #BrainHealth #MSBlog

“I have just got back from the 23rd European Charcot Meeting, in Baveno, Italy. I was invited to present our ‘Brain Health – Time matters in MS’ policy document. My presentation was a bit rushed as I was expecting to have 30 minutes, but was told to cut it down to 15 minutes just before I presented. As promised, my slides are below for you to see and/or download. I received a lot of positive feedback about my presentation and the policy document. One neurologist from Canada will be using the policy document next week as part of a lobby in Canada to get more effective 2nd-line treatments available earlier for people with MS. A Dutch neurologist asked why the Netherlands were not more involved with this initiative; they can be all they need to do is sign-up and pledge their support. A Swiss neuroradiologist volunteered to help with the imaging, and MRI monitoring component, of the policy document. All these anecdotes are good news for me as it indicates that people are engaging with the initiative. I sincerely hope 'Brain Health in MS' as treatment concept evolves over the next 12-24 months into something much bigger. Our vision for the document is for it become a real change agent so that we actually ‘create a better future for people with MS and their families’.”

“If you haven’t pledged your support for the policies please do via our Brain Health website.”

CoI: multiple

Your Genes can protect you from MS

Bettencourt A, Carvalho C, Leal B, BrĂ¡s S, Lopes D, Martins da Silva A, Santos E, Torres T, Almeida I, Farinha F, Barbosa P, Marinho A, Selores M, Correia J, Vasconcelos C, Costa PP, da Silva BM. The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.J Immunol Res. 2015;2015:948723.

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1(∗)15 (OR = 2.17) and HLA-DRB1(∗)03 (OR = 1.81) alleles with MS, HLA-DRB1(∗)03 with SLE (OR = 2.49), HLA-DRB1(∗)01 (OR = 1.79) and HLA-DRB1(∗)04 (OR = 2.81) with RA, HLA-DRB1(∗)07 with Ps + PsA (OR = 1.79), HLA-DRB1(∗)01 (OR = 2.28) and HLA-DRB1(∗)08 (OR = 3.01) with SSc, and HLA-DRB1(∗)03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1(∗)13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1(∗)13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1(∗)13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1(∗)13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

When I was is Boston I visited the Harvard MS group and saw one of the bags for screening that could be done and was very impressed by the range of assays. One of the assays was to test for the HLA-DR type. We know that HLA-DR2 (serotype) or HLA-DRB1*1501 (geneotype) is the major susceptibility allele for MS. I bet we at Barts don't do this as a regular check.

How is a T cell stimulated.

This study shows that HLA-DR13 is unrepresented in MS and it looks like people with DR13 delete self reactive cells.

So I say hurray, because I am HLA-DR7 and HLA-DR13. I know this because I donated my blood for experiments and I was found not to respond to myelin oligodendrocyte glycoprotein. Is this why I have ot got MS yet? 

However MD2 is HLA-DR3 and HLA-DR4 and this is the major, major risk factor for type 1 diabetes and rheumatoid arthritis. 

However as MD2 hasn't got either of these things yet, it shows you that having MS risk genes does not mean you will get MS. Likewise just because you have MS, does not mean that our children will get MS.

JCV virus infection at presentation of MS

Delbue S, Tadeo CS, Elia F, Ferrante P. Intervirology. JC Virus Replication at the First Symptoms of Multiple Sclerosis: A Case Report. 2015;58:278-282.

Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of unknown aetiology, in which viruses have been suggested as aetiological/triggering agents. The attention to the association between viruses and MS has been rekindled by the development of progressive multifocal leukoencephalopathy in natalizumab-treated MS patients. Here we report the case of a woman with JC virus (JCV) replication in the cerebrospinal fluid, blood and urine collected at the first symptoms of MS and during several follow-up visits. This observation shows that JCV can be associated with MS without a relation with natalizumab treatment, although the triggering role of JCV in some cases of MS will require further studies.

This is interesting. Someone with MS with frank viral infection. Is this MS or is it PML masqurading as MS. Is MS due to the effective killing of JC virus infected oligodendrocytes so that it remains undetected? Could it remain undetected when so many people have looked for virus. People say that JC virus only infects 50% of people  with MS, but anti-viral ELISAs and PCR are not infallable. However if this were the case once you have Stem cell transplants would we not get PML raising its head. Maybe ProfG can take a break from enjoying Lake Maggoire to tell us why not.