Predicting Autoimmunity after Alemtuzumab

Azzopardi L, Thompson SA, Harding KE, Cossburn M, Robertson N, Compston A, Coles AJ, Jones JL. Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Dec. doi: 10.1136/jnnp-2013-307042. [Epub ahead of print]

OBJECTIVE:We have previously shown that autoimmunity following alemtuzumab treatment of multiple sclerosis can be predicted by high baseline serum interleukin IL-21 (IL-21), as measured using a now ‘redundant’ enzyme linked immunosorbent assay (ELISA). Here we ask whether currently available ELISAs have similar prognostic value.
DESIGN:Serum IL-21 from 141 individuals with relapsing remitting multiple sclerosis was measured using the now ‘redundant’ IL-21 ELISA and five further currently available kits. All patients had been treated with alemtuzumab; 61/141 had developed secondary autoimmunity.
RESULTS:The ‘redundant kit’, and one current kit, confirmed higher baseline serum IL-21 in patients with autoimmunity (542 pg/mL vs. 222 pg/mL and 53.1 pg/mL vs. 9.3 pg/mL respectively) and showed positive correlation. However, only the ‘redundant’ kit had predictive utility.
CONCLUSIONS: Currently available IL-21 ELISA kits should not be used to counsel individuals with multiple sclerosis considering treatment with alemtuzumab.

An ELISA that detected soluble interleukin 21 was used and was suggested to predict, in part, whether autoimmunity may develop after alemtuzumab treatment. An ELISA against interleukin 21 is may contain a capture IL-21 antibody that is stuck to plastic and a detect anti-body that has a dye attached to it. So you add blood which contains IL-21 that is bound to the capture antibody and then you add the detect antibody that can now bind to the captured IL-21 and the more IL-21 in the blood the more that is captured the more detection signal you get. You then take a known amount of IL-21 and put this in the assay and then you can work out how much is in the blood. You can make these ELISAs up or eventually a company will make a kit, which is easier to do and generally gives more consistent results. This study tests a few commercial kits and none of them performed as well as the original ELISA and they had n predictive value. There are clearly problems with the ELISAs as they are not accurately detecting the levels in the blood ~500pg/ml in one verses 50pg/ml. This paper says that you can’t use current commercial kits to predict whether you will get autoimmunity after campath. Was the original interpretation correct.

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