Juxtaposition of IL-1β and IFN-γ expression and apoptosis of keratinocytes in adult-onset Still’s disease

ABSTRACT

Backgroud: Recently, atypical persistent skin eruptions (APSEs) have been documented as a new manifestation of adult-onset Still’s disease (AOSD), with a unique pathological feature of necrotic keratinocytes in the upper third of the epidermis, but the mechanism has not been elucidated. The aim of this study was to explore the potential mechanism of the unique pathological phenomenon of APSEs.

Methods: Clinical and pathological data from 26 AOSD patients with APSEs and 6 with evanescent skin eruptions (ESEs) were reviewed. Fourteen APSE biopsies and 6 ESE biopsies were selected for multi-spectrum immunohistochemistry with 5 disease controls and 5 healthy controls.

Results: The unique pathological manifestation was present in all APSE patients but was hardly found in ESE patients. There were more CD4 + T-cells infiltrated in the dermis of APSEs than in the dermis of ESEs. IL-1β and IFN-γ were specifically expressed in the upper third of the epidermis and were juxtaposed to the loci of the necrotic keratinocytes.

Conclusion: Our findings showed important cellular and molecular derangements related to the APSE-specific pathological phenomena and helped to understand the pathogenesis of dyskeratosis in the epidermis. The findings could also pave a way to explore an effective intervention to this potentially life-threatening disorder.

KEYWORDS:

• Adult onset Still’s disease
• atypical persistent skin lesions
• dyskeratosis
• IL-1β
• IFN-γ

Article highlights

• APSEs appear a unique pathological feature of necrotic keratinocytes in the upper third layer of the epidermis, differentiated from classical evanescent skin eruptions (ESEs).

• In APSE, IL-1β and IFN-γ were specifically expressed in the upper third of the epidermis and were juxtaposed to the loci of the necrotic keratinocytes.

• More CD4+ T-cells infiltrated in the dermis of APSEs than in the dermis of ESEs suggests that CD4+ T-cells might be involved in the formation of APSEs in AOSD.

• ESEs and APSEs could represent the two ends of a spectrum in terms of expression of multiple cytokines, duration of skin eruptions, and severity of inflammatory events, with cytotoxicity occurring predominantly in the APSEs.

Acknowledgments

We wish to thank every author contribute to this study. We also thank to Wei Liu who helped to revise this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

The dateset of this study was showed in Mendeley Data, please check it through this link: http://dx.doi.org/10.17632/csp4939d3j.2.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81430074, No. 81602767, No. 81830097, No. 81861138016, No. 81974481), National Basic Research Program of China (No. 2014CB541904), the Natural Science Foundation of Hunan Province (2017JJ3453, 2017SK2042, 2018JJ3756) the National Key research and Development Program of China (2016YFC0903900), and the Natural Key Clinical Specialty Construction Project of National Health and Family Planning Commission of the People’s Republic of China.