Recent research has found that distinct antigen-specific T-cell responses may play a role in pathogenesis of psoriasis and atopic eczema. Judith Leavy reports
A German study recently published in the New England Journal of Medicine, suggests that distinct antigen-specific T-cell responses may play a role in the pathogenesis of psoriasis and atopic eczema.
The study is based on a rare group of patients who suffer from both diseases. As the results show, the T-cells of the immune system in the skin activate an inflammatory programme that causes either atopic eczema or psoriasis. The researchers evaluated three patients with both psoriasis and eczema and noted that the T-cells found in psoriatic lesions differed from those found in eczema lesions. The findings suggest that these T-cells migrate to the skin in response to distinct environmental triggers, not that the skin cells themselves are abnormal in either inflammatory condition.
The most prevalent autoimmune disease in the United States, psoriasis affects up to 7.5 million Americans, with more than 100,000 people in Ireland also suffering from the disease. It is thought to arise from a combination of genetic and environmental triggers, according to the National Psoriasis Foundation. Eczema, on the other hand, is also thought to be an allergic response and often occurs simultaneously in those with asthma or food allergies, according to the American Academy of Allergy, Asthma and Immunology. Current psoriasis treatments, which include both topical and systemic drugs, aim to suppress the body’s immune response and slow down the skin cell growth cycle that leads to its trademark red, scaly plaques. Eczema treatments can involve both medications and lifestyle changes that cut itching, inflammation and worsening of the condition.
The simultaneous occurrence of psoriasis driven by type 1 helper T (Th1) cells and type 17 helper T (Th17) cells and atopic eczema dominated by type 2 helper T (Th2) cells is rare. The study, conducted by researchers at the Centre for Allergy and Environment in Munich (ZAUM), the Helmholtz Zentrum München and the Techni-sche Universität München (TUM), Germany, evaluated patients with concomitant psoriasis and atopic eczema and patients with psoriasis and allergic contact dermatitis.
Clinical presentations, personal histories, laboratory findings, and the results of epicutaneous patch testing were used to make a diagnosis. Eczema and psoriasis lesions were used to obtain punch biopsy specimens. A histological examination was carried out, and the cytokine profile of T-cell lines was determined. In addition, secretions of interferon-gamma, interleukin-4 (IL-4), interleukin-17 (IL-17), and interleukin-22 (il-22) levels were quantified using an enzyme-linked immunosorbent assay.
Sensitised patients with psoriasis had a reaction to epicutaneous allergen challenge, with clinically and histologically verified eczema lesions containing a large number of allergen-reactive T-cells. These findings, the authors wrote, support a causative role for T-cells triggered by specific antigens in both psoriasis and atopic eczema.
Investigators studied three patients with both atopic dematitis (AD) and psoriasis. The histological examination of skin samples from AD and psoriatic lesions showed characteristics of the respective diseases. Psoriasis plaques contained large numbers of Th1 and Th17 cells secreting cytokines, γ-interferon and IL-17. The AD samples contained relatively higher numbers of Th2 and Th22 cells secreting IL-4 and IL-22.
Koebner reactions can cause psoriasis in traumatised skin. After a patch test challenge with house-dust antigen, the invading T-cells were mostly Th2 cells, and two patients developed eczema (but not psoriasis). In nickel patch tests, the infiltrate in nickel-sensitive patients was dominated by Th1 and Th17 cells, and many T-cells in T-cell clones that were established from extracted lymphocytes reacted with nickel. Only a few cells extracted from psoriasis lesions reacted with nickel in these same patients.
The researchers found that there was a reaction to an epicutaneous allergen challenge in sensitised patients with psoriasis, with clinically and histologically verified eczema lesions containing a large number of allergen-reactive T-cells. The cytokine profile of T-cells derived from psoriasis and atopic eczema lesions were different, with Th1 and Th17 cells being higher in the psoriasis lesions, and Th2 and Th22 cells higher in atopic eczema lesions. Psoriasis-derived T-cell lines had higher levels of interferon-gamma and IL-17 secretions, whereas IL-4 levels were higher in T-cells from atopic eczema lesions in vitro. In patient one, previous adalimumab treatment had cleared the psoriasis but with a flare of the AD; now, both conditions responded to ustekinumab. Both diseases responded to cyclosporine in patient two. Treatment and response were not specified for the third patient.
Based on these results, the authors concluded that intrinsic epithelial abnormalities are not involved in the pathogenesis of AD or psoriasis. Instead, they propose that T-cells migrate into skin in response to distinct but different antigen triggers.
Dr Jerry Bagel, a spokesman for the National Psoriasis Foundation and Associate Clinical Professor of Dermatology at Columbia University in New York City, said the research indicates that eczema and psoriasis are clearly distinct entities, but there is some crossover immunologically.
The ability to determine which antigens stimulate each condition would likely take years but may prevent the disorders from developing in predisposed people.
The study also found that all eczema lesions, but none in psoriasis, harboured Staphylococcus aureus, confir-ming that T-cells in psoriasis appear to prompt an innate immune response that is different from that seen in eczema.
The authors commented that the results advance understanding but also cause confusion as patients are not supposed to have both conditions. They hope that results could lead to more direct testing to see if patients have an immune system alteration. The more that is learned about how the immune system responds to insults from the external world, the greater the possibility of being able to adjust steps along the way, or developing medications that minimise side-effects and maximise safety.
Professor Ring, co-author and Director of the Department of Dermatology and Allergology in Biederstein believes that “this study highlights the critical role of T-cells in psoriasis”.
The scientists now aim to find out which T-cell molecules are responsible for triggering these diseases. “Clearly, future therapy strategies should focus on the impairment of the immunological memory,” said Prof Carsten Schmidt-Weber, Director of the Helmholtz Zentrum München and the Department of Dermatology and Allergology, Biederstein, Technische Universität München.