July 1, 2009
The leukemia drug Campath (aka alemtuzumab) has been shown in clinical trials to have impressive efficacy against MS. It kills off large numbers of various immune cells circulating in the body; these cells then regenerate over time. One downside of the drug that was seen in the MS trials is that it increases the risk of certain autoimmune conditions that target the thyroid and blood components. A team of scientists studied factors that might influence the development of these conditions and found that higher levels of the signalling molecule IL-21 may be to blame (open access article -- read it here!).
The team analyzed serum samples taken from people on the trial and analyzed IL-21 levels from those who did and didn't develop autoimmunity. They found that in samples taken both before and after treatment with alemtuzumab, those who did develop autoimmunity had higher IL-21 levels than those who did not. They also found certain variants in the IL-21 gene that appear to increase IL-21 levels, so it may be that whether someone develops autoimmunity after immune cell depletion is genetically determined.
The team also found that:
The authors conclude that higher levels of IL-21 boosts T cell turnover, thereby increasing the risk that a person will generate auto-reactive T cells and develop new forms of autoimmunity. They suggest that these findings could be developed further into a method for providing advice to people with MS concerning use of Campath. An interesting question raised by this study is why IL-21 increases the risk of thyroid autoimmunity and not other types of autoimmune disease -- the authors speculate that IL-21 may drive some disease activities but not others.