Nickel acts as an adjuvant during cobalt sensitization

Bonefeld, Charlotte M.; Nielsen, Morten Milek; Vennegaard, Marie T.; Johansen, Jeanne Duus; Geisler, Carsten; Thyssen, Jacob P.

doi:10.1111/exd.12634

Cited by 38 publications

(24 citation statements)

References 10 publications

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“…Despite the high prevalence of concomitant nickel and cobalt allergy (63), it has been shown that human nickel-specific T cells do not cross-react with cobalt (42, 57). We found that nickel induced more local inflammation than cobalt in mice exposed to only the individual metal during challenge, indicating that nickel is a more potent adjuvant than cobalt (62). Interestingly, it has been shown that chromium [Cr(VI)] is more cytotoxic and that it accumulates more within keratinocytes than nickel and cobalt (64,65).…”

Section: The Effect On the Immune Responsementioning

confidence: 88%

“…Addition of 1% NiCl 2 during sensitization with 10% CoCl 2 led to a strong increase in the challenge response to 10% CoCl 2 as compared with the challenge response in mice sensitized with 10% CoCl 2 alone, as measured by ear thickness and proliferation of B and T cells ; that is, a synergistic or – in this case – ‘adjuvant’ effect was noted. In contrast, addition of 1% CoCl 2 to 10% NiCl 2 during the sensitization response led to only a minor increase in CD8 + T cell proliferation following challenge with 10% NiCl 2 as compared with mice sensitized with 10% NiCl 2 alone . T cell cross‐reactivity does not seem to explain these observations.…”

Section: Effects Of Mixing Contact Allergensmentioning

confidence: 90%

“…Interestingly, very little is known about how co-exposure to metals affects the immune response to an individual metal used in the alloy. In a study investigating how co-exposure to nickel and cobalt affected the challenge response to either nickel or cobalt, we found that co-sensitization boosted the challenge response to both metals (62). Addition of 1% NiCl 2 during sensitization with 10% CoCl 2 led to a strong increase in the challenge response to 10% CoCl 2 as compared with the challenge response in mice sensitized with 10% CoCl 2 alone, as measured by ear thickness and proliferation of B and T cells (62); that is, a synergistic or -in this case -'adjuvant' effect was noted.…”

Section: The Effect On the Immune Responsementioning

confidence: 99%

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Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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SummaryAllergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.Key words: fragrances; hair dyes; metals; mixtures of allergens.Contact allergy is very frequent in the European population, as shown by Diepgen et al., who found that 27% were sensitised to common allergens (1). This may lead to allergic contact dermatitis if exposure exceeds the individual threshold of response.The allergic response is frequently directed towards nickel, cobalt, fragrances, hair dye chemicals, or preservatives. Many of these molecules are categorized as weak to moderate allergens -this term will be used throughout the article for (pre/pro)haptens (2). Surprisingly, even 'weak to moderate' allergens do induce allergic contact dermatitis in many people. This indicates that exposure parameters, such as dose and exposure frequency, are critical. Interestingly, consumers are rarely exposed to one isolated allergen, but are more often exposed to mixtures of allergens, for example in the form of metal alloys, cosmetics, and cleaning agents (3, 4). The impact of being exposed to a mixture of allergens instead of a single allergen has not been well studied. Studies from our group have suggested that exposure to mixtures of allergens has a great impact on the immune responses to single allergens within the mixture. In this review, we will discuss the current knowledge on how exposure to mixtures of contact allergens affects the immune system by (i) altering the chemical properties of single allergens in the mixtures, (ii) changing the inflammatory response, and (iii) affecting T cell activation, proliferation, and differentiation. Furthermore, we will discuss other factors, such as the presence of irritants, a disrupted skin barrier, local skin inflammation, and local skin memory, that could increase the response to allergens. Finally, we will discuss the clinical impact of

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Section: The Effect On the Immune Responsementioning

confidence: 88%

Section: Effects Of Mixing Contact Allergensmentioning

confidence: 90%

Section: The Effect On the Immune Responsementioning

confidence: 99%

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Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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“…The moderately increased response to DNFB and cinnamal in ft/ft mice is probably mediated by steady‐state skin inflammation, as both allergens are likely to penetrate skin with and without filaggrin proteins and degradation products. Co‐exposure to mixtures of allergens and irritants increases the immune response, so, similarly, we suspect that the existing inflammation in ft/ft skin could reduce the inflammatory threshold for DNFB and cinnamal, and thereby explain the moderately enhanced responses to these allergens …”

Section: Discussionmentioning

confidence: 99%

Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

et al. 2018

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Background: Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown.Objectives: To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. Methods:The immune responses to nickel, 2,4-dinitrofluorobenzene (DNFB), cinnamal and pphenylenediamine were assessed in ft/ft and wild-type (WT) mice. The amounts of nickel in the skin of ft/ft and WT mice were determined 20 hours after nickel exposure. The effect of blocking either the interleukin (IL)-17A pathway or the IL-1 pathway on the response to nickel in ft/ft mice was evaluated.Results: Increased responsiveness to nickel, DNFB and cinnamal was observed in ft/ft mice as compared with controls. A reduced amount of nickel was found in the skin of ft/ft mice as compared with WT mice, suggesting increased nickel absorption by the skin of ft/ft mice. Blocking either the IL-17A pathway or the IL-1 pathway reduced nickel responsiveness in ft/ft mice.Conclusions: These findings suggest that the increased nickel responsiveness associated with epidermal filaggrin deficiency is mediated by a combination of increased nickel penetration and the steady-state inflammation found in the skin of filaggrin-deficient mice. K E Y W O R D Sallergic contact dermatitis, filaggrin, IL-17A, IL-1β, nickel | INTRODUCTIONAllergic contact dermatitis (ACD) is a common inflammatory skin disease that occurs in sensitized individuals who are cutaneously exposed to small chemicals, that is, contact allergens, such as metals, fragrances, and hair dye components. Nickel allergy is the most frequent form of ACD, affecting 14.5% of the adult European population. 1 Filaggrin, which is a quantitatively and qualitatively important protein of the stratum corneum (SC), aggregates keratin filaments during the terminal differentiation of keratinocytes, leading to compaction of the cells. 2 Common loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris, and dramatically increase the risk of atopic dermatitis (AD). [2][3][4] Studies have also shown that FLG mutations might be associated with nickel allergy and ACD, as well as stronger nickel patch test reactions. 5-7 Although the mechanisms mediating the association between nickel allergy and FLG mutations are unknown, increased epidermal penetration of nickel because of a reduction in chelating histidine is a possibility. 8,9 Epidermal deficiency of filaggrin is also associated with steadystate skin inflammation. 10-14 For example, increased levels of interleukin (IL)-1β are found in the SC of uninvolved skin and in blister fluid of

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“…The clinical relevance of her cobalt and palladium reactions is uncertain. Many nickel‐allergic patients are co‐sensitized to cobalt and cross‐react with palladium . Palladium and nickel both belong to Group VIII of the periodic table .…”

Section: Discussionmentioning

confidence: 99%

Allergic contact mucositis caused by metal: a covertly located permanent dental retainer

Shutty

Scheinman

2017

Contact Dermatitis

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Nickel acts as an adjuvant during cobalt sensitization

Cited by 38 publications

References 10 publications

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

Allergic contact mucositis caused by metal: a covertly located permanent dental retainer

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