A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese diabetic (NOD) mice.

The interplay between diet and immune parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up-regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on NKG2D expression is not known. We studied, by fluorescence activated cell sorter (lymphoid tissues) and reverse transcription-quantitative polymerase chain reaction (intestine and pancreatic islets), if a gluten-free diet (GF diet) from 4 weeks of age or a gluten-free diet introduced in breeding pairs (SGF diet), induced changes in NKG2D expression on DX5(+) (CD49b) natural killer (NK) cells, CD8(+) T cells and in intestinal and islet levels of NKG2D and ligands in BALB/c and non-obese diabetic (NOD) mice. Gluten-free NOD mice had lower insulitis (P < 0·0001); reduced expression of NKG2D on DX5(+) NK cells in spleen and auricular lymph nodes (P < 0·05); and on CD8(+) T cells in pancreas-associated lymph nodes (P = 0·04). Moreover, the level of CD71 on DX5(+) NK cells and CD8(+) T cells (P < 0·005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (P < 0·05). Differences in intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data show that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.

Immune responses to hair dyes containing toluene-2,5-diamine.

BACKGROUND: Toluene-2,5-diamine (PTD) is the most frequently used dye in oxidative hair dyes on the Scandinavian market. However, little is known about immune responses to PTD-containing oxidative hair dyes. OBJECTIVES: To study immune responses induced by PTD-containing hair dyes in mice. METHODS: Immune responses against two different permanent hair dye products containing 1·60% (w/w) and 0·48% (w/w) PTD within the colour gel, and various concentrations of pure PTD were studied. The local inflammatory response was measured by ear swelling and cell infiltration, and T- and B-cell infiltration and proliferation was determined in the draining lymph nodes. RESULTS: Concentration-dependent immune responses were seen to PTD both in the skin and draining lymph nodes. The hair dye containing 1·60% PTD induced strong local inflammation and caused T- and B-cell infiltration and proliferation as well as an increased number of regulatory T cells in the draining lymph nodes. In contrast, the hair dye containing 0·48% PTD induced skin inflammation but only minor responses in the draining lymph nodes. CONCLUSIONS: Consumer-available PTD-containing permanent hair dyes can be potent immune activators inducing both pro- and anti-inflammatory responses. The outcome of the response is dependent on allergen dose, amount of additional allergens and exposure regime.

The association between contact sensitization and atopic disease by linkage of a clinical database and a nationwide patient registry.

BACKGROUND: Experimental studies have shown that individuals with atopic dermatitis are likely to have suppressed contact sensitivity secondary to their disease whereas some clinical and epidemiological studies have shown that individuals with atopic dermatitis might have a higher prevalence of contact sensitization than controls. The objective was to study the association between contact sensitization and, respectively, atopic dermatitis and asthma using clinical databases. METHODS: Record linkage of two different registers was performed: (i) a tertiary hospital register of dermatitis patient's patch tested for contact sensitivity and (ii) the Danish National Patient Register containing nationwide hospital discharge diagnoses and outpatient contacts. RESULTS: An inverse association was found between contact sensitization and, respectively, presumed severe atopic dermatitis (OR, 0.70; 95% CI, 0.61-0.81) and asthma (OR, 0.61; 95% CI, 0.42-0.90) when linkage was performed. Inverse associations were found for all groups of chemicals and metals except for sensitization to fragrances and topical drugs where positive associations were identified. A significant positive association between fragrance sensitization and presumed mild-moderate atopic dermatitis was also found when data from hospital register only were used, suggesting an overall higher prevalence of fragrance sensitization in patients with atopic dermatitis. CONCLUSIONS: Our findings support that patients with severe atopic dermatitis and asthma have an overall lower prevalence of contact sensitization when compared with controls, whereas mild-to-moderate disease does not suppress contact sensitization. The prevalence of contact sensitization to fragrance chemicals was higher in patients with atopic dermatitis. Patients should be instructed to avoid scented moisturizers and products containing highly sensitizing substances.

Contact sensitization to common haptens is associated with atopic dermatitis: new insight.

BACKGROUND: It has been much debated whether atopic dermatitis (AD) is associated with contact sensitization as past findings have been conflicting. A positive association might change our clinical practice. OBJECTIVES: To investigate the association between AD and contact sensitization taking the likely route of allergen exposure into account. METHODS: Questionnaire and clinical data from a cross-sectional study performed in a general population in Copenhagen. In total, 3202 adults aged 18-69 years were patch tested, filaggrin genotyped for 2282del4 and R501X and questioned about AD. RESULTS: The variable 'contact sensitization to at least one allergen, but not nickel and thimerosal' was significantly associated with AD (odds ratio 2·53, 95% confidence interval 1·59-4·04). The higher prevalence of contact sensitization was driven mainly by fragrance chemicals. In a subanalysis in nonpierced women, a positive association was also found for nickel sensitization. Nickel and thimerosal sensitization may introduce bias in data analysis as these allergies often develop following skin piercing where the skin compartments are bypassed. CONCLUSIONS: We suspect that individuals with self-reported AD from this study mainly had mild disease. However, clinicians should be aware of increased levels of contact sensitization in individuals with AD. Patch testing should therefore be considered at an early point in individuals with a history of AD and active disease. The fundamental relationship between atopic disease and environmental chemical exposure may be of a more complex and intimate nature than previously supposed.

Impaired hapten sensitization in patients with autoimmune disease.

An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We sensitized 68 adult individuals (23 patients with psoriasis, 22 patients with diabetes and 23 healthy controls) with diphenylcyclopropenone (DPCP) and assessed challenge responses with visual scoring and ultrasound. Skin biopsies from challenged skin were investigated for differences in down-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I of being sensitized to 0·18 [95% confidence interval (CI): 0·039-0·85], P = 0·031 and 0·74 (95% CI: 0·548-1·008), P = 0·056, respectively. A high degree of forkhead box P3-positive (FoxP3(+) ) cells were found in biopsies of positively challenged reactions, but only limited numbers in negatively challenged reactions, with no difference among the groups. No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis.

The prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure.

BACKGROUND: Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water-soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. OBJECTIVES: To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. PATIENTS AND METHODS: A retrospective analysis of patch test data was performed (n = 16,228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a chi(2) test. Logistic regression analyses were used to test for associations. RESULTS: The prevalence of chromium allergy decreased significantly from 3.6% in 1985 to 1% in 1995 (P(trend) < 0.001) but increased to 3.3% in 2007 (P(trend) < 0.001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12.7% in 1989-1994 to 3.0% (P < 0.01) in 1995-2007, whereas the frequency of relevant leather exposure increased significantly from 24.1% during 1989-1994 to 45.5% during 1995-2007 (P < 0.02). CONCLUSIONS: Chromium allergy is currently increasing in Denmark due to leather exposure.

Inverse relationship between contact allergy and psoriasis: results from a patient- and a population-based study.

BACKGROUND: An inverse association between contact allergy and autoimmune diseases has been suggested. Psoriasis is an autoimmune disease and it has been debated whether contact allergy is less prevalent among patients with psoriasis. Previous studies have shown conflicting results. OBJECTIVES: To examine a possible association between contact allergy and psoriasis in two conceptually different epidemiological studies. PATIENTS AND METHODS: Two study populations were included: (i) a clinic-based register linkage study population, achieved by record linking information from the Danish National Hospital Registry identifying patients with psoriasis with information on contact allergy from a comprehensive patch test database of 15,641 patients; and (ii) a population-based cross-sectional study population organized in 1990, 1998 and 2006 and obtained by random samples from the Danish Central Personal Register. Information was obtained by questionnaire and patch testing of 4989 subjects. RESULTS: An inverse association was found between a psoriasis diagnosis and a positive patch test in both studies. The odds ratio for a person with a psoriasis diagnosis of having a positive patch test was, adjusted for sex and age, 0.58 [95% confidence interval (CI) 0.49-0.68] and 0.64 (95% CI 0.42-0.98), respectively, in the two studies. CONCLUSIONS: The finding of an inverse association between psoriasis and contact allergy may express opposite immunological mechanisms and calls for additional research in this field.

Inverse relationship between allergic contact dermatitis and type 1 diabetes mellitus: a retrospective clinic-based study.

AIMS/HYPOTHESIS: Contact allergy (CA) is a disease induced and maintained by environmental factors, which mainly has a Th2 pattern in its chronic form. Environmental factors play a major role in CA, while genetic factors are of minor importance. Type 1 diabetes is an autoimmune disease of the islets of Langerhans, which has a Th1 cytokine pattern and in which modulators of risk are both genetic and environmental. To investigate whether environmental exposure to chemicals leading to CA could influence the risk of type 1 diabetes, we conducted a retrospective clinic-based study of patients subjected to diagnostic patch testing of CA. METHODS: We undertook a retrospective clinic-based study of 13,315 patients who were patch-tested between 1985 and 2003, and linked it with the Danish National Patient Registry containing diabetic mellitus discharge diagnoses from 1987 to 2003. The 13,315 patch-tested patients gave rise to 4,848 CA patients. Using logistic regression, we calculated odds ratios for persons with CA of having type 1 diabetes. RESULTS: Type 1 diabetes was diagnosed in 229 of the patch-tested patients. CA patients had a reduced risk of having type 1 diabetes, with an odds ratio 0.62 (95% CI 0.46-0.86). After adjusting for sex and age, the odds ratio was 0.63 (95% CI 0.47-0.86). CONCLUSIONS/INTERPRETATION: An inverse relationship between CA and type 1 diabetes was found. Thus there may be a protective effect of having CA in relation to the risk of type 1 diabetes, or vice versa type 1 diabetes may lead to tolerance rather than hypersensitivity. Alternatively, these two diseases may share common genetic factors, although at present these are unknown.