Comparative serum cytokine profiling identifies distinct immunological features of atopic keratoconjunctivitis

Abstract Background Atopic dermatitis (AD) is frequently complicated by atopic keratoconjunctivitis (AKC), yet the cutaneous disease severity does not consistently parallel ocular involvement. This study investigated whether severe AKC is associated with circulating cytokine patterns distinct from those observed in patients with AD without severe ocular involvement (AD-only). Methods Serum samples were collected from four cohorts: healthy controls ( n = 11), patients with AD-only ( n = 11), patients with AKC ( n = 11), and patients with Stevens-Johnson syndrome (SJS) with severe ocular complications ( n = 15). Serum concentrations of 48 cytokines, chemokines, and growth factors were assessed using a multiplex bead-based immunoassay. Results Compared with AD-only, patients with AKC had significantly higher serum concentrations of SCGF-β and TRAIL and lower concentrations of eotaxin. Compared with SJS, AKC was similarly associated with higher SCGF-β and TRAIL and lower eotaxin concentration. IL-16, CTACK and IL-2Ra were elevated in AKC compared with healthy controls but did not differ between AKC and AD-only, whereas MIF was elevated in AD-only, AKC, and SJS compared with healthy controls. These findings demonstrate heterogeneous patterns of circulating inflammatory mediators across the study groups rather than a uniform cytokine response associated with ocular inflammation. Conclusions Severe AKC was associated with higher circulating SCGF-β and TRAIL and lower eotaxin concentration compared with AD without severe ocular involvement and with non-atopic severe ocular disease. These findings identify candidate circulating mediators associated with severe AKC and warrant validation in larger, appropriately age-matched cohorts.

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Publication Details

Journal
Allergy Asthma and Clinical Immunology
Published
2026-11-11
DOI
https://doi.org/10.1186/s13223-026-01085-3
Primary Topic
Dermatology and Skin Diseases
Type
article
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article

Comparative serum cytokine profiling identifies distinct immunological features of atopic keratoconjunctivitis

Chie Sotozono, Mayumi Ueta, Takayuki Jujo, Shigeru Kinoshita et al.
Allergy Asthma and Clinical Immunology
Dermatology and Skin Diseases
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Comparative serum cytokine profiling identifies distinct immunological features of atopic keratoconjunctivitis

Chie Sotozono, Mayumi Ueta, Takayuki Jujo, Shigeru Kinoshita, Jun Kunisawa, Hitoshi Kawashima, Takayuki Miyano, Hinako Nanri, Koji Hosomi, Tsuyoshi Ishii, Hiromi Nishigaki, Ka Man Tse, Yoshihiro Takai
article en

Abstract

Abstract Background Atopic dermatitis (AD) is frequently complicated by atopic keratoconjunctivitis (AKC), yet the cutaneous disease severity does not consistently parallel ocular involvement. This study investigated whether severe AKC is associated with circulating cytokine patterns distinct from those observed in patients with AD without severe ocular involvement (AD-only). Methods Serum samples were collected from four cohorts: healthy controls ( n = 11), patients with AD-only ( n = 11), patients with AKC ( n = 11), and patients with Stevens-Johnson syndrome (SJS) with severe ocular complications ( n = 15). Serum concentrations of 48 cytokines, chemokines, and growth factors were assessed using a multiplex bead-based immunoassay. Results Compared with AD-only, patients with AKC had significantly higher serum concentrations of SCGF-β and TRAIL and lower concentrations of eotaxin. Compared with SJS, AKC was similarly associated with higher SCGF-β and TRAIL and lower eotaxin concentration. IL-16, CTACK and IL-2Ra were elevated in AKC compared with healthy controls but did not differ between AKC and AD-only, whereas MIF was elevated in AD-only, AKC, and SJS compared with healthy controls. These findings demonstrate heterogeneous patterns of circulating inflammatory mediators across the study groups rather than a uniform cytokine response associated with ocular inflammation. Conclusions Severe AKC was associated with higher circulating SCGF-β and TRAIL and lower eotaxin concentration compared with AD without severe ocular involvement and with non-atopic severe ocular disease. These findings identify candidate circulating mediators associated with severe AKC and warrant validation in larger, appropriately age-matched cohorts.

Allergy Asthma and Clinical Immunology
Kyoto Prefectural University of Medicine (JP), National Institute of Biomedical Innovation, Health and Nutrition (JP), Rohto Pharmaceutical (Japan) (JP), Osaka Metropolitan University (JP)
Dermatology and Skin Diseases
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