Allergy: Genetics and IgE

00:01 I’ve already mentioned that genetics are important in the development of allergy.

00:06 So let’s take a couple of minutes to look at some of the genes that have been identified.

00:13 Polymorphisms of genes encoding Pattern Recognition Receptors have been described in patients with allergy.

00:22 So have polymorphisms in the gene encoding the cytokine thymic stromal lymphopoietin.

00:30 Polymorphisms of the MHC particularly HLA-DQ polymorphisms.

00:37 And polymorphisms in the transcription factor SMAD3.

00:42 Other polymorphisms that have been described are ones for the genes encoding the interleukin-2 receptor β-chain, and indeed for the cytokine itself interleukin-2.

00:54 As well as polymorphisms of the genes for the interleukin-33 receptor and for interleukin-33.

01:02 And as these reactions get going with the dendritic cell stimulating Th2 cells.

01:09 And with the involvement perhaps of induced regulatory T-cells trying to dampen down the allergic response.

01:17 If the balance goes towards the development of an allergic response, the Th2 cells will become dominant with the production of cytokines such as interleukin-4, interleukin-5, interleukin-13.

01:29 Eosinophils will be stimulated, B-cells will be stimulated.

01:33 Those B-cells will class switch to IgE production differentiate into plasma cells that will secrete the IgE antibody that is so characteristic of the Type I hypersensitivity reaction.

01:47 This will then bind to the FCεR1, the high affinity IgE receptor.

01:53 And maybe you won’t be too surprised to hear that polymorphisms in that particular receptor have also been linked to the development of allergic disease.

02:02 And again, mast cells just like Th2 cells have a receptor for interleukin-33 and therefore that polymorphism is acting at several different levels during the allergic response.

02:16 And again, TSLP is influential in modulating the activity of mast cells, just like it can act on dendritic cells.