Contact allergy to nickel: Perspectives for laboratory diagnosis

Background: Contact allergy to nickel affects approximately 60 million EU citizens. A reliable laboratory test for contact allergy is still missing, possibly due to misunderstandings about the key pathological processes. In many classical textbooks, contact allergy has been described as a Th1-dependent process, with IFN-gamma as the key cytokine. However, most attempts to diagnose contact allergy on the basis of allergen-specific IFN-gamma secretion have failed. Instead, results from a previous study (Spiewak et al. 2007) have suggested that measuring allergen-specific response of IL-5 and IL-13-secreting lymphocytes is more effective in discriminating Ni-allergic patients from healthy persons.

Aim: To identify a laboratory test (or combination of tests) that would discriminate Ni-allergic patients from healthy people most accurately.

Methods: 68 patients undergoing routine patch testing volunteered to donate blood for the study. We analysed, which of 12 compared in vitro methods predicted most accurately a patient to be nickel-allergic. Positive history and patch test served as gold standard. Furthermore, relationships were analysed between Ni-specific IFN-gamma and IL-5 secretion from patients' leukocytes and patch test score (=intensity of local Ni-specific skin inflammation).

Results: IL-2 ELISpot after culturing the donor's leukocytes with addition of IL-7 and IL-12 proved best for predicting Ni-allergy (GDA regression model: sensitivity 86%, specificity 100%, overall concordance 93%). This was followed by a complex formula including results of IL-13 ELISpot, IL-5 ELISA, and IFN-gamma ELISA (86%, 100%, 86% respectively). Interestingly, we have found that Ni-specific IL-5 secretion correlated significantly with patch test score (logistic regression: p=0.05, generalized coefficient of determination R2=0.33), while there was no such relationship for IFN-gamma (p=0.20). In practical terms, an increase of 10 pg/ml Ni-specific IL-5 secretion by leukocytes is associated with a 24.2% increase in the predicted risk for a patient to have a higher patch test score.

Conclusions: The correlation between Ni-specific IL-5 production and patch test results reinforces the previous observation that "type 2" lymphocytes are important players in this process. Altogether the above observations suggest that it is indeed possible to develop an in vitro test that could efficiently predict the presence and severity of contact allergy to nickel.

Related articles:

1. Spiewak R, Moed H, von Blomberg BME, Bruynzeel DP, Scheper RJ, Gibbs S, Rustemeyer T. Allergic contact dermatitis to nickel: Modified in vitro test protocols for better detection of allergen-specific response. Contact Dermatitis 2007, 56 (2): 63-69.
2. Spiewak R. Patch testing for contact allergy and allergic contact dermatitis. Open Allergy J 2008, 1: 42-51.

Links:

Institute of Dermatology, Krakow, Poland

International Photopatch Test Course, Krakow 2009

English-speaking dermatologist in Krakow (Cracow), Poland

Deutschsprechender Hautarzt in Krakow (Krakau), Polen

Sensimun (formerly Celimun)