Can MS be adoptively transferred?

Barts-MS rose-tinted-odometer ★★★ 

How much of your mother is inside you?

Cells from the maternal circulation (your mother) cross the placenta into the foetal circulation (you) and set-up shop in your brain and body. This phenomenon is called maternal microchimerism and is very common and may be more common in people with autoimmune disease. The implications, or hypothesis, is that cellular autoimmunity may be transmitted in this way. Could this explain why MS occurs at more than twice the familial rate in children of mothers, when compared to children of fathers, with MS?  

These maternal cells can be found in men by looking for female cells, i.e those that contain more than two X chromosomes.

The small study below does not show a difference between finding these cells in the brains of men with and without MS. Maybe the investigators’ should look in the immune compartment to see if maternal B- and/or T-cells could be found? Just maybe autoimmunity, or specifically MS, can be transferred from mother to child via the adoptive transfer of autoreactive B- and T-cells through the placenta? If this was the case then children born to pwMS on natalizumab may be more at risk? Why? Natalizumab is the one DMT that does not deplete the so-called peripheral autoreactive cells; in fact, natalizumab keeps them circulating in the periphery in high numbers hence making them more likely to cross the placenta in the foetal circulation. 

The only way to find this out if children of natalizumab-treated pwMS are increased risk of getting MS is to start and run a pregnancy registry to collect data longterm and to follow-up all the children born to pwMS to see what happens to them in the future.

The good news is that Dr Ruth in our group will be doing just that a and will be launching a national UK pregnancy register with the aim of also collecting the outcomes of the children.

Another more sinister way to answer this question is via state surveillance, or Big Brother, which happens in Nordic countries. Sweden has probably the most mature system of state-sponsored surveillance and they could link all their databases to answer this question in the near future. 

Snethen et al. Maternal micro-chimeric cells in the multiple sclerosis brain. Mult Scler Relat Disord. 2020 Jan 9;40:101925. doi: 10.1016/j.msard.2020.101925. 

Maternal microchimeric cells (MMC) pass across the placenta from a mother to her baby during pregnancy. MMC have been identified in healthy adults, but have been reported to be more frequent and at a higher concentration in individuals with autoimmune diseases. MMC in brain tissue from individuals with autoimmune neurological disease has never previously been explored. The present study aims to identify and quantify MMC in adult human brain from control and multiple sclerosis (MS) affected individuals using fluorescent in situ hybridization (FISH) with a probe for the X and Y chromosomes. Post mortem brain tissue from 6 male MS cases and 6 male control cases were examined. Female cells presumed to be MMC were identified in 5/6 MS cases and 6/6 control cases. Cell specific labelling identified female cells of neuronal and immune phenotype in both control and active MS lesion tissue. This study shows that female cells presumed to be MMC are a common phenomenon in the adult human brain where they appear to have embedded into brain tissue with the ability to express tissue-specific markers.

CoI: multiple