Even though Dr. Compston may continue to assert that his research proves a genetic correlation to the HLA locus and to t cell activation in MS, there is one thing he cannot explain.

Identical twins.

A recent study of 3 sets of indentical twins, (called "MZ twins" for monozygotic) where one twin had MS, and the sibling did not, brought forward the following information:

There was no discernable genetic difference between the immune system of the twin with MS, and the twin without MS.

Here, we report the genome sequences of one MS-discordant MZ twin pair and messenger RNA (mRNA) transcriptome and epigenome sequences of CD4+ lymphocytes from three MS-discordant, MZ twin pairs. No reproducible differences were detected between co-twins among ~3.6 million single nucleotide polymorphisms (SNPs) or ~0.2 million insertion-deletion polymorphisms (indels). Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and indel genotypes, or expression of ~19,000 genes in CD4+ T cells. Only two to 176 differences in methylation of ~2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to ~800 methylation differences between T cells of unrelated individuals and several thousand differences between tissues or normal and cancerous tissues. In the first systematic effort to estimate sequence variation among MZ co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first female, twin and autoimmune disease individual genome sequences reported.

We sought genetic, epigenetic or transcriptomic differences between CD4+ T cells of twin siblings that might explain MS-discordance. While MS is a neurologic disease, T cells are fundamentally involved in its pathophysiology1. However, no reproducible differences in SNPs, indels, CNVs, gene expression levels or sequences aligning to viral genomes were detected between CD4+ T cells of co-twins. 

Other epigenetic mechanisms, differences within lymphocyte subsets, mono-allelic differences or other tissues were not examined. These caveats aside, however, MZ twins lacked genetic, epigenetic or transcriptomic differences in T cells to explain MS-discordance.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862593/

Get that?  There was no difference in t cells between the twin with MS and the twin without.  How can Dr. Compston assert that MS is about the t cells, when the healthy twin had the same, exact t cells, and no MS?  Truth is, he can't.

Here's what the researcher who conducted this study said--

“We find no smoking gun on the genetic level,” said National Center for Genome Resources geneticist Stephen Kingsmore, co-author of the study published April 28 in Nature.

The research cost $1.5 million, and the scientists took 18 months to sequence 2.8 billion DNA units in each twin, and determine whether they came from the mother or father. Most genomic comparisons look for differences in a just handful of suspect genes, and even whole-genome approaches don’t differentiate between parental contributions.

The researchers also analyzed the twins’ CD4 cells, a type of white blood cell that plays a central role in the development of MS. In these cells, the researchers sequenced epigenomes — chemical instructions that turn genes on and off — and transcriptomes, or a chemical record of genes that are actively coding proteins.

These multiple layers of information represent the cutting edge of genomic analysis, and are expected to reveal what rougher tools cannot. “This was a technical tour de force, and potentially represents a new way of looking at disease states,” said Kingsmore. Nevertheless, they found no differences.

http://www.wired.com/wiredscience/2010/04/multiple-sclerosis-twinmystery/

No genetic difference in the immune system of the twin with MS and the twin without.

Maybe the researchers should look at venous malformations?  Or environmental factors?

One environmental factor in twins with MS has been studied---vitamin D.

Each of the nine sun exposure–related activities during childhood seemed to convey a strong protection against MS within MZ twin pairs.

http://www.wellnesspasadena.com/Vitamin%20d%20research/Childhood_sun_exposure_influences_risk_of_multiple_sclerosis_in_monozygotic_twins_--_Islam_et_al._69__4___381_--_Neurology_01.pdf  

Joan