CD52 depletion in the beasties....implications for human use.

von Kutzleben S, Pryce G, Giovannoni G, Baker D. Depletion of CD52 positive cells inhibits the development of CNS autoimmune disease, but deletes an immune-tolerance promoting CD8 T cell population. Implications for secondary autoimmunity of alemtuzumab in multiple sclerosis. Immunology. 2016 Dec 7. doi: 10.1111/imm.12696. [Epub ahead of print]


Yes I know I posted this before but now

The fully formatted paper is now readable and can be downloaded for FREE 
(CLICK HERE)

Yes this paper is set in the beasties, but we believe that it has implications for humans in that it suggests that whilst Alemtuzumab can block the development of relapsing CNS autoimmune disease, it blocks the formation of immunological tolerance. 

(a) This may be the basis for secondary B cell mediated autoimmunities in MS
  
These diseases will occur in about 50% of people within 5-7 years of treatment

These include ITP meaning that your blood needs to be screened once a month for 4 years after the last injection.

Many of the autoimmunities relate to thyroid problems of either an over active (Graves thyroiditis) of under active (Hashimotos thyroiditis) thyroid. 

(b) This may be the basis for anti-drug autoimmunity

These occurs in about 90% of people within a year of treatment and occur within 1 month in most people. 

These are both binding and importantly about 90% of people making binding antibodies make neutralizing antibodies.

These may contribute to infusion reactions (although this will be masked by the paracetamol, anti-histamines and steroids given during the infusions...therefore ensure that you consider this especially if receiving multiple infusions) and the lack of efficacy in some people if neutralizing antibodies are persistent.

Didn't know about this latter aspect...not surprising because they forgot to mention this in the pivotal trial reports!

COI: We are authors. Genzyme supported some of the studies.

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