Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

Autor: Koduri MA; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India., Pingali T; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India., Prasad D; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India., Singh V; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India., Singh S; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India., Shanbhag SS; The Shantilal Shanghvi Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India., Basu S; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.; The Shantilal Shanghvi Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India., Singh V; Centre for Ocular Regeneration (CORE), Prof. Brien Holden Eye Research Centre (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India.; The Shantilal Shanghvi Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Aug; Vol. 79 (8), pp. 2128-2143. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1111/all.16126
Abstrakt: Purpose: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
Methods: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity.
Results: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization.
Conclusion: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.
(© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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