Cross-reactivity among some metals in a murine metal allergy model

Background: Information concerning cross-reactivity among metal allergens is scarce. We previously devised a murine metal allergy model using lipopolysaccharide (LPS) as an adjuvant. LPS reduces the minimum allergy-inducing concentration (MAIC) of metals at both the sensitization and the elicitation steps. Objectives: Here, we examined allergic cross-reactivity among some metals in this murine model, and compared the effects of ultrapure (99.99% or more) and low purity (93-99%) metal salts. Methods: A mixture of a metal salt and Escherichia coli LPS was injected intraperitoneally into BALB/c mice (0.25 mL per mouse). Ten days later, metal salts (with or without LPS) were challenged to ear pinnas (20 lL per ear), and ear swelling was measured. Results: Among the ultrapure metals tested (Ni, Pd, Co, Cr, Cu and Au), only Ni and Pd cross-reacted. In this cross-reaction, their MAICs were at the same level. Combined challenge with Ni and Pd at sub-MAICs (but not at higher concentrations) produced an additive effect. Surprisingly, mice sensitized with low purity Ni reacted to all the tested low purity metals (Ni, Pd, Co and Cr), and the low purity metals were shown to contain contaminant metals. Conclusions: In our model: (i) Ni and Pd (members of the same group in the periodic table of elements) cross-react with each other, (ii) this cross-reaction may depend on true and false antigens forming metal-protein complexes with similar spatial geometries, (iii) Co, Cr, Cu and Au do not cross-react with each other, (iv) in low purity materials, trace contaminant metals may be sufficient to evoke allergy, and thus (v) high purity metal salts should be considered for use in clinical patch testing.