Usefulness of lymphocyte transformation test and in vitro cytokine release in differentiating between independent and cross‐reacting nickel/palladium allergy

Abstract

Background Often concomitant patch test (PT) reactivity to palladium (Pd) and nickel (Ni) is found. Objectives To determine whether lymphocyte transformation test (LTT) could be useful in discrimination between cross‐reacting or distinct PT results, and to compare the results with in vitro cytokine production upon Pd or Ni stimulation. Materials and Methods The study population consisted of two groups: 13 individuals with Pd PT reactions (10 with concomitant Ni PT reaction, 3 individuals with only Pd PT reactivity) and 10 Ni/Pd PT negative individuals. LTT and assessment of cytokine release (interferon‐gamma, interleukin‐5 [IL‐5], IL‐8, IL‐17A, tumor necrosis factor alpha) by cytometric bead assay were performed. Results All 10 patients with positive PT to Ni and Pd showed positive LTT to Ni (P < .05) as compared with the 10 Pd/Ni PT negative patients—but had no significant LTT reaction to Pd. In all, 9 out of 10 Pd/Ni PT negative patients were also LTT negative to Ni and 10 out of 10 to Pd. In the 3 only Pd PT reactors 2 out of 3 remained LTT negative to Ni and 0 out of 3 to Pd. As a major finding, cytokine production gave clearly enhanced IL‐5 response to Ni in Ni PT positive individuals (P < .05), whereas Pd PT reactivity was not linked with such enhanced IL‐5 production in vitro to Pd. Conclusions Pd and Ni sensitization are mostly found concomitantly, and cross‐reactivity is questioned. By different LTT reactions and particularly IL‐5 production in vitro, predominant Ni sensitization becomes more evident.

Immunological Mechanisms of Metal Allergies and the Nickel-Specific TCR-pMHC Interface

“…Regarding Ni-specific T cells, often, similar responses have been observed in nonallergic and allergic individuals, especially for CD4+ T cells [89,115,132,[177][178][179]. The frequency of Ni-specific CD4+ T cells correlates with the used Ni concentrations and varies between ~0.00005%, 0.02% and 0.1% at Ni 2+ concentrations close to zero, ~40 µM, and 200 µM, respectively [115,132,180].…”

“…Among these patients, mouth mucosal diseases were more common than skin diseases [88]. PdCl 2 is the most frequent (3%) allergen of the "dental metal series" detected in dental technicians with occupational ACD [89]. The incidence of Pd allergies has frequently been explained through cross-reactivity since isolated allergy to Pd is rare [87].…”

“…The frequency of Ni-specific CD4+ T cells correlates with the used Ni concentrations and varies between ~0.00005%, 0.02% and 0.1% at Ni 2+ concentrations close to zero, ~40 µM, and 200 µM, respectively [115,132,180]. However, no concentration has been determined which optimally distinguishes allergic from non-allergic individuals [89,177,181]. Local in vivo concentrations in the skin or lymph nodes remain unknown.…”

“…Co seems to activate a similar or slightly smaller percentage of T cells compared to Ni, as judged from proliferation-based assays, [181][182][183] while Pd-specific T cell frequencies have hardly been investigated [89,184]. Unless limited dilution cultures are used, proliferation-based assays do not allow a direct assessment of the initial frequencies of reactive T cells.…”

Development and initial validation of a modified LTT assay in patients with DRESS and AGEP

“…The detection of IL-5 has thus far proven useful as a surrogate marker for hypersensitivity to metals only such as nickel and palladium. (24).…”