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. PBMC from nickel allergic patients and controls were stimulated with nickel under type 1, 2 and 17 skewing culture conditions; levels of 33 cyto‐ /chemokines were analysed and related to medical history of nickel contact dermatitis and nickel patch test result. A broad spectrum of 21 type 1, 2, 9,17, 22 and antigen presenting cell related factors was associated with nickel allergy. IL‐5 production under type 2 skewing conditions and lymphocyte proliferation are most potent biomarkers for nickel allergy.