SNPs associated with allergic contact dermatitis to weak antigens, metals, antigens metabolized in skin, and polysensitization

Examination of over 1400 single nucleotide polymorphisms to explore association with genes that may be involved in the mechanism of allergic contact dermatitis. We examined four clusters of contact allergens: allergens that are non-or weak sensitizers in the local lymph node assay (propylene glycol, vanillin, eugenol, paraben mix); metals (Ni, Co, Cr, Au); allergens metabolized in the skin (PPDA, corticosteroids); and polysensitization defined as positive patch tests to 3 or more non-cross-reacting allergens. We also looked for SNPs associated with history of childhood flexural dermatitis (atopic dermatitis) and dyshidrotic eczema, both of which are Th2 skewed immune reactions often associated with allergic contact dermatitis.
We review our findings in "Weak Sensitizers may be Associated with CD80 Polymorphisms-Implications for Systemic Contact Dermatitis" JID Innovations 2025.
CD80 is expressed on many cells including eosinophils and dendritic cells such as innate lymphoid cells 2 that may facilitate sensitization to antigens that are not processed via conventional dendritic cells in the local lymph node. This innate "trained immunity" may allow ingestion to trigger recall via NKT cells at prior sites of skin contact of the same allergen. Systemic contact dermatitis of the eczematous type (as opposed to the erythema multiforme-type triggered by inhaled potent allergens like poison ivy or epoxy) is usually triggered by ingestion of weak antigens such as foods or food additives and is usually Th2 skewed (Ahuja K, Issa CJ, Nedorost ST, Lio PA. Is Food-Triggered Atopic Dermatitis a Form of Systemic Contact Dermatitis? Clin Rev Allergy Immunol. 2024 Feb;66(1):1-13. doi: 10.1007/s12016-023-08977-x.)
In contrast, we also found that dyshidrotic eczema, which is also Th2 skewed but often triggered by dietary exposure to metal allergens of moderate potency, is associated with genetic variants in TSLP, suggesting that these allergens are process in the local lymph node leading to antigen specific immunoglobulin. CD80 variants were not associated with history of dyshidrotic eczema.
Systemic contact dermatitis to allergens such as foods or food additives may explain food-triggered atopic dermatitis. The immunology is complex and involves sensitization on chronically inflamed skin, innate and/or adaptive antigen presenting cells, CLA+ cells such Th2 and/or NKT cells, and IL-31.