Nickel allergy is associated with a broad spectrum cytokine response

BACKGROUND: Nickel‐induced proliferation or cytokine release by peripheral blood mononuclear cells may be used for in vitro diagnosis of nickel allergy. OBJECTIVES: Aim of this study was to explore the nickel‐specific cytokine profile to further elucidate the pathogenesis of nickel allergic contact dermatitis (ACD) and to identify potential new biomarkers for nickel ACD. METHODS: Peripheral blood mononuclear cells from patients and controls were cultured with T‐cell skewing cytokine cocktails and/or nickel. Cytokine and chemokine concentrations were assessed in culture supernatants using validated multiplex assays. Specific cytokine production was related to history of nickel allergy and patch‐test results. RESULTS: Twenty‐one of the 33 analytes included in the analysis were associated with nickel allergy and included type1 (TNF‐α, IFN‐γ, TNF‐β), type 2 (IL‐3, IL‐4, IL‐5, IL‐13), type 1/2 (IL‐2, IL‐10), type 9 (IL‐9), type 17/1 (IL‐17A[F], GM‐CSF, IL‐21) and type 22 (IL‐22) derived cytokines as well as the T‐cell/antigen presentation cell derived factors Thymus and activation regulated chemokine (TARC), IL‐27 and IP‐10. Receiver operator characteristics (ROC) analysis showed that IL‐5 was the strongest biomarker for nickel allergy. CONCLUSIONS: A broad spectrum of 33 cytokines and chemokines is involved in the allergen‐specific immune response in nickel allergic patients. IL‐5 remains, next to the lymphocyte proliferation test, the strongest biomarker for nickel allergy.