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Omer Iqbal, Charles S Bouchard, makio iwashima, Sean Till, Ping Bu; The Potential Roles of IL-33 and TGF-β1 in the Pathogenesis of Stevens - Johnson syndrome/ Toxic Epidermal Necrolysis. . Invest. Ophthalmol. Vis. Sci. 2017;58(8):192.
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© ARVO (1962-2015); The Authors (2016-present)
The exact mechanism of keratinocyte apoptosis in the pathogenesis of Stevens - Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) characterized by drug-induced mucocutaneous reactions and ocular involvement leading to corneal blindness remains unclear. We tested the hypothesis that increased levels of Interleukin-33 (IL-33) and transforming growth factor beta one (TGF-β1) in the plasma and also their increased expression in the skin of patients with biopsy confirmed SJS/TEN compared to that with lichen planus as controls obtained and archived from a clinical study may play important roles in keratinocyte apoptosis.
Under a current, Loyola IRB approved protocol clinical study, collected and archived unstained slides (n=8) of skin from patients with biopsy confirmed SJS/TEN and lichen planus as controls (n=6) were used for this study. Immunohistochemical analysis was performed using IL-33 and TGF-β1 antibodies followed by imaging on a DeltaVision microscope. ELISA analysis was used to determine the levels of IL-33 and TGF-β1 expression in multiple citrated plasma samples totaling 78 from SJS/TEN patients (n=14). Statistical analysis was performed using linear regression analysis, ANOVA, and Turkey’s post-hoc tests on STA-TA software.
Immunofluorescent microscopy of SJS/TEN skin biopsy samples revealed elevated levels of both TGF-β1and IL-33 in the epithelium compared to lichen planus skin biopsy samples as controls. However, ELISA analysis of SJS/TEN patient plasma samples showed no marked elevation of TGF-β1 or IL-33 compared to normal human plasma (p= 0.41 and 0.26 respectively). The results of this study may enhance our understanding of the pathogenesis of SJS/TEN and lead to the development of new treatment modalities for this disease.
Our results are consistent with our hypothesis that increased expression of IL-33 andTGF-β1 in the skin of patients with SJS/TEN compared to lichen planus as controls play important roles in keratinocyte apoptosis. However, their corresponding undetectable levels in plasma by the ELISA technique needs to be evaluated in freshly obtained larger number of plasma samples. Further large-scale studies are warranted to validate these results.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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