People often claim, in a colloquial sense, that they are "allergic to everything".

Is it possible to have a full-fledged IgE mediated allergic response to very small molecules? I was always under the impression that the smallest antigen was a oligopeptide, but is it possible for someone to be allergic to something like isopropanol, glucose, or another small organic molecule?

How about allergies to metals, as I know those are fairly common, would they be mediated through a similar mechanism?


2 Answers 2


At one of my previous companies that raised antibodies to proteins and post-translational modifications, we found that 6-8 amino acids was generally the smallest peptide length required for an epitope. Anything much smaller than that won't induce the cross-linking or conformational changes required for signal transduction and an allergic response. As WYSIWYG notes, allergies to small molecules/atoms are formed via hapten-carrier interactions. These can be covalent, as in the nickel-transferrin example, or as a result of denaturation/chemical modification, as likely happens with people who are allergic to things like isopropanol or bleach.

I very much doubt that there can be such a thing as a glucose allergy, as it is so ubiquitous in the body that such antibodies/T-cells would be negatively selected long before they could do any damage.

  • $\begingroup$ Yes, the glucose example was a figment of my imagination, I just wondered if it was theoretically possible, but your point about negative selection is surely true. $\endgroup$
    – jonsca
    Apr 18, 2013 at 22:49
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    $\begingroup$ @jonsca you are correct. However, plasma glucose can spontaneously react with the amine side chains of proteins and form pro-inflammatory advanced glycation endproducts. Certain immune cells have receptors for AGEs. So although AGE-drive inflammtion is not an adaptive (antigen driven) immune response, it is immune mediated. $\endgroup$
    – PlaysDice
    Apr 1, 2014 at 0:55

Small molecules do not have antigenic properties but they can elicit immune response by binding to a "carrier" protein. The small molecule is called a Hapten. An epitope forms at the protein-hapten binding interface.

Nickel acts like a hapten and elicits immune response by binding to proteins like transferrin, albumin etc.

Other metals also cause allergy in a similar way.


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