Psoriasis Targeted Therapy: Characterization of Interleukin 17A Expression in Subtypes of Psoriasis
October 2015 | Volume 14 | Issue 10 | Original Article | 1133 | Copyright © 2015
Eric Lee MD, Mina Zarei MD, Charlotte LaSenna BS, Gabriel Villada MD, and Paolo Romanelli MD
Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
INTRODUCTION: Psoriasis is a chronic, inflammatory autoimmune disease that affects about 3% of the general population in the United States with 17% suffering from moderate to severe psoriasis. The disease process is believed to be mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations including Interleukin (IL)-17, IL-22, and Interferon (IFN) γ. IL-17 plays an important role in psoriasis. In this study we evaluated the expression of IL-17A in variants of psoriasis including plaque, palmoplantar, scalp, pustular, and guttate subtypes via immunohistochemistry (IHC).
METHODS AND MATERIALS: A search of the University of Miami Dermatopathology database was performed to identify all available patient specimens within the various subtypes of psoriasis. IL-17A IHC staining was performed using 4 μm paraffin skin sections. 1:25 dilution of IL-17A antibody was used. Stained slides were analyzed using a semi-quantitative scoring method ranging from negative to three plus.
RESULTS: Palmoplantar and pustular psoriasis cases showed consistently strong IL-17A staining. Plaque psoriasis cases showed intermittent to strong IL-17A staining. The results in the scalp and guttate psoriasis cases showed variable results.
CONCLUSION: The results of our study suggests the significant role of the cytokine IL-17A in the development of palmoplantar and pustular psoriasis. However, scalp and guttate subtypes showed variable expression from negative to strongly positive, which demonstrates a case by case basis expression of IL-17A. Therefore, exploring the IHC characterization of subtypes of psoriasis will help dermatologists better understand the pathogenesis of each subtype and help clinicians optimize treatments.
J Drugs Dermatol. 2015;14(10):1133-1136.
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Psoriasis is a chronic, inflammatory autoimmune disease that ffects about 3% of the general population in the United States with 17% suffering from moderate to severe psoriasis.1 Psoriasis is a complex disease with environmental, immunological and genetic components. The disease process is characterized by hyperproliferation of keratinocytes and is mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations including Interleukin (IL)-17, IL-22, and Interferon (IFN) γ.2,3 In a genetically predisposed individual, there is an initial trigger that activates the innate immune system with the release of antimicrobial peptides (AMPs). Subsequent activation of dendritic cells stimulate helper T-cell (Th) 1 and Th17, These autoreactive T-cells proliferate and migrate into the skin, releasing inflammatory cytokines, chemokines, and AMPs which initiate the inflammatory cascade resulting in psoriasis.4
There are several studies on the role of these cytokines in the development of psoriasis as well as the utility of immune inhibition with a variety of biologic agents for the treatment of psoriasis. TNF-α blockers are the first generation biologic agents that have been used for this purpose. Recently, neutralization of human IL-23 in a xenotransplant mouse model of psoriasis showed that IL-23-dependent inhibition of psoriasis is comparable to anti-TNF agents.5
IL-17 also plays a role in psoriasis. In fact, increased IL-17 levels in patients with psoriasis may enhance neutrophil migration and survival in the dermis and drive angiogenesis in synergy with TNF-α and the release of inflammatory cytokines.6- 10 In a murine model in which imiquimod was used to induce psoriasis-like skin lesions, IL-17 expression increased in the epidermis. Interestingly, in this model, mice lacking the IL-17-receptor did not develop psoriasis-like lesions.11
Neutralization of IL-17 in psoriasis patients demonstrated histologic improvement in biopsy specimens including a decrease in acanthosis, keratinocyte proliferation, and dermal lymphoyctic infiltrate.12 In this study we evaluated the expression of IL-17A in variants of psoriasis via immunohistochemistry (IHC). These variants include plaque, palmoplantar, scalp, pustular, and guttate psoriasis.
METHODS AND MATERIALS
A search of the University of Miami Dermatopathology database was performed to identify all available patient specimens