{"id":1179,"date":"2026-01-15T08:16:00","date_gmt":"2026-01-15T08:16:00","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/01\/15\/cinders-ugly-sister-gets-her-foot-in-the-shoe-or-is-it-trail-blazing\/"},"modified":"2026-01-15T08:16:00","modified_gmt":"2026-01-15T08:16:00","slug":"cinders-ugly-sister-gets-her-foot-in-the-shoe-or-is-it-trail-blazing","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2026\/01\/15\/cinders-ugly-sister-gets-her-foot-in-the-shoe-or-is-it-trail-blazing\/","title":{"rendered":"Cinder\u2019s Ugly Sister gets her foot in the Shoe or Is it trail blazing?"},"content":{"rendered":"
Tweet<\/a><\/div>\n

Thomas et al. Anoctamin-2-specific T cells link Epstein-Barr
virus to multiple sclerosis. Cell (2026), https:\/\/
doi.org\/10.1016\/j.cell.2025.12.032<\/p>\n

Epstein-Barr virus (EBV) infection constitutes a prerequisite for multiple sclerosis (MS) development, and cross-reactivity between EBV nuclear antigen 1 (EBNA1) and anoctamin-2 (ANO2) antibodies was previously demonstrated in persons with MS (pwMS). Here, we show that ANO2-specific CD4+ T cells are more frequent in pwMS. Immunization of SJL\/J mice with ANO2 or EBNA1 led to cross-reactive CD4+ T cell and antibody responses. ANO2 pre-immunization led to exacerbated experimental autoimmune encephalomyelitis (EAE), an effect mediated by CD4+ T cells, as confirmed by adoptive transfer experiments. T cell clones with cross-reactivity to EBNA1 and ANO2 could be isolated from natalizumab-treated pwMS, and sequencing of EBNA1- and ANO2-specific T cell receptors (TCRs) revealed a significant repertoire overlap.We thus report the first mechanistic evidence that EBNA1 CD4+ T cells can target the MS autoantigen ANO2<\/em>, thereby establishing a link between EBV infection and neuroinflammation.<\/p>\n

What causes MS? <\/strong><\/p>\n

The view has been made that immmune responses to EBNA1 of Epstein bar virus cross react to proteins in the MS. About 2-3 years ago when the MS-World eventually went EBV mad, there was little discussion on what happened to the years of work telling us that MS was a T cell -mediated disease to myelin basic protein and why there was a sudden change of direction and we were told to be convinced that what causes MS was an antibody response to a small part of EBV that cross reacted with the bit of a target called GlialCam that was inside the astrocyte or to a lesser extent oligodendrocytes and liver cells.<\/em> <\/p>\n

It didn’t occur in every body leaving other candidate possibilities and sure enough we have had a few other suggested such as alpha B crystallin and Anoctamin-2 to mention a few. Now I would say that not everybody can repeat the original or subsequent findings. But this process of cross reactivity is called molecular mimicry, <\/strong>which was originally based on an idea based on observations of T cell target binding.<\/p>\n

I can buy the idea that Epstein Barr Virus is the cuprit in the causal pathway and I can also buy tthe idea that there is some cross reactivity of immune reponses to EBV can cross react with CNS target. You can shown it, but it is it causal?<\/p>\n

ProfG is not so sure of its importance and asked me what problems do I see with the idea? Now what every I say, it is an opinion and could be wrong and you would want a counter view. If you look hard enough to show this, I am sure you can find it. But it does not say it is causal but could be an effect of the cause. You also have to ask what other targets do EBV targeting antibodies bind, to as we have recently had a link between EBV and Lupus and other conditions.<\/p>\n

So cross reactivity can be shown but if all you do it prove the idea and do nothing to disprove the idea (easier) you simply do what you want to give you the answer you want.<\/p>\n

So the Ugly Sisters want to marry the Prince and so they squeeze their feet in to the dainty shoes of Cinderella and claim their prize. But if you measure the shoe and get the proper size of foot that would fit the shoe and then measure the ugly sisters shoe and find they are abit big, or too small for that matter, you start to get the idea that the ugly, or for that matter beautiful, sister is not the belle of the ball, who left her shoe with Prince Charming. Now I am being flipant her…But in reality these days very little is done to question dogma, to show that the idea is not correct. <\/p>\n

Now the post is not really about this paper<\/p>\n

These days nobody does any work, so what does ChatGTP say to the question?<\/h4>\n
Why is anoctamin-two a good autoantigen target for multiple sclerosis<\/strong> (first answer given below)<\/h5>\n

“Anoctamin-2 (ANO2, also called TMEM16B) has been proposed as a good candidate autoantigen in multiple sclerosis (MS)<\/strong> because it fits several features that make a protein capable of driving CNS-specific autoimmunity. Here are the key reasons, step by step.<\/p>\n

1. Strong and selective expression in the CNS<\/strong><\/p>\n

ANO2 is a calcium-activated chloride channel<\/strong> that is:<\/p>\n