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Biological Chemistry

Key Step Found In Latex Allergy

Allergen dimerizes before allergic response is triggered

by Raychelle Burks
July 30, 2007 | A version of this story appeared in Volume 85, Issue 31

Credit: shutterstock
Credit: shutterstock

LATEX GLOVES are widely used in laboratories, but some wearers are allergic to them. It turns out that certain small molecules used in latex manufacturing become, in the finished products, irritants that can cause allergic contact dermatitis (ACD). Researchers at the National Institute for Occupational Safety & Health (NIOSH) and Portland State University, in Oregon, now have elucidated the allergy-triggering mechanism of one of the worst of these allergens, 2-mercaptobenzothiazole, or MBT(Chem. Res. Toxicol., DOI: 10.1021/tx700139g). The findings may open new routes to preventing ACD.

MBT is used to accelerate polymerization during latex manufacture, and small amounts of the compound remain in finished products.

Compounds such as MBT are too small to provoke an allergic response on their own, but they can bind to proteins, and the resulting complexes can trigger allergy attacks. Such piggybacking allergens are called haptens, and the binding process is known as haptenation. A direct haptenation mechanism "only explains about 35-40% of the known chemical allergens," says Paul D. Siegel, a bioorganic chemistry team leader at NIOSH. MBT fell into the unexplained group.

Using MBT-containing latex glove material, common workplace chemicals such as hydrogen peroxide, and human serum albumin (HSA), Siegel's team found that MBT can be oxidized by various agents to a disulfide-linked dimer. Allergy trouble starts with the dimer, which is reduced by HSA at a specific cysteine residue, Siegel says. This reduction breaks the dimer, liberating one MBT fragment and leaving the other bound to HSA through a disulfide bond.

Chemical and animal studies conducted by Siegel's team indicate that MBT alone is not enough to provoke an allergic response. He notes that data from his research also bolster the hypothesis that the formation of disulfide bonds during MBT's haptenation with body proteins is critical to eliciting ACD. These findings suggest that small, thiol-containing molecules have the potential to trigger allergic responses, Siegel says.

This work will be helpful to physicians and scientists investigating contact dermatitis, suggests physician Joseph F. Fowler Jr., president of the North American Contact Dermatitis Group.



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