Downregulation of interferon-γ-induced protein 10 in the tears of patients with Stevens-Johnson syndrome with severe ocular complications in the chronic stage

Ueta, Mayumi; Nishigaki, H; Sotozono, Chie; Kinoshita, Shigeru

doi:10.1136/bmjophth-2017-000073

Cited by 19 publications

(19 citation statements)

References 8 publications

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“…IP-10 was significantly downregulated in all SJS/TEN cases compared to the normal control subjects, similar to the findings in previous reports 14 , 22 . Moreover, IP-10 was significantly downregulated in SJS/TEN cases with conjunctivalization and neovascularization.…”

Section: Discussionsupporting

confidence: 91%

“…Another studies noted upregulation of IP-10 in eyes with evaporative DED and downregulation of IP-10 in eyes with chronic GVHD 24 , 25 . We have found that in eyes with SJS/TEN, IP-10 was downregulated as same as GVHD 14 .…”

Section: Discussionmentioning

confidence: 71%

“…Tear samples were collected on Schirmer Tear Production Measuring Strips (Showa Yakuhin Kako Co., Ltd., Tokyo, Japan) according to our previously reported method 14 . They were immersed in 100 µL Tris-buffered saline, we measured the titre of the above-listed cytokines in 50 µL of TBST containing the tears.…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, we investigated the cytokines in tears of SJS/TEN cases with SOC, and found that in the acute phase, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were dramatically increased 13 , while in the chronic phase, there was a significant downregulation of interferon-γ-induced protein 10 (IP-10), as well as upregulation of IL-6, IL-8, eotaxin, and macrophage inflammatory protein-1 beta (MIP-1β) compared with the tears of normal control subjects 14 .…”

Section: Introductionmentioning

confidence: 99%

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Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

Yoshikawa

Ueta

Nishigaki

et al. 2020

Sci Rep

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This study aimed to clarify predictive biomarkers of mild and severe ocular complications of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears. In 121 chronic-phase SJS/TEN eyes, cytokines in tear samples collected using Schirmer test strips were measured, and ocular sequelae severity was evaluated using an Ocular Surface Grading Score (OSGS) involving 7 components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening), with findings categorized into grades 0–3 (maximum total OSGS: 21). Changes in cytokines between the mild and severe groups (mild: total OSGS of 10 or less, severe: total OSGS of 11 or more), and changes between SJS/TEN cases with and without each of the 7 components, were compared. In the severe group, there was significant upregulation of interleukin (IL)-8 (P < 0.01) and Granzyme B (GrzB) (P < 0.05). IL-8 was significantly upregulated in eyes with conjunctivalization, neovascularization, or opacification, GrzB was upregulated in eyes with keratinization, interferon-γ-inducible protein 10 (IP-10) was downregulated in eyes with conjunctivalization or neovascularization, and IL-1α was upregulated in eyes with opacification (all: P < 0.05). IL-8 and IP-10 was involved in conjunctivalization and neovascularization, while GrzB was involved in keratinization. IL-8 and GrzB in tears may reflect SJS/TEN-related ocular sequelae severity.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

Yoshikawa

Ueta

Nishigaki

et al. 2020

Sci Rep

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“…In the acute stage, patients with SJS/TEN with SOC manifest severe conjunctivitis with corneal and conjunctival erosion and a pseudomembrane in addition to skin eruption and erosion. Despite healing of the skin lesions, in the chronic stage of SJS/TEN with SOC, ocular surface inflammation persists6 as do ocular surface complications including conjunctival invasion into the cornea, symblepharon, ankyloblepharon and dry eye 3 7. It is not easy for ophthalmologists to render a differential diagnosis of SJS or TEN when patients present in the chronic stage because the vesiculobullous skin lesion expressed in the acute stage has healed by the chronic stage.…”

Section: Introductionmentioning

confidence: 99%

Gene expression analysis of conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage

et al. 2019

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ObjectiveTo investigate the pathology underlying the ocular surface complications of patients with Stevens-Johnson syndrome (SJS) in the chronic stage.Methods and analysisUsing oligonucleotide microarrays, we performed comprehensive gene expression analysis of the conjunctival epithelium of patients with SJS in the chronic stage (n=3). The controls were patients with conjunctival chalasis (n=3). We confirmed the downregulation and upregulation of transcripts of interest by quantitative real-time PCR (RT-PCR) assay. The expression of ocular surface protein with significantly upregulated transcripts was assessed immunohistochemically.ResultsCompared with the controls, in the conjunctival epithelium of patients with SJS, 50 transcripts were downregulated by less than one-tenth (analysis of variance (ANOVA) p<0.05). Transcripts MUC7, PIGR, HEPACAM2, ADH1C and SMR3A were downregulated by less than one-fiftieth. 65 transcripts were upregulated more than 10- fold; the difference between patients with SJS and the controls was significant (ANOVA p<0.05). There were 14 transcripts that were upregulated more than 50-fold; they were SERPINB4, KRT1, KRTDAP, S100A7, SBSN, KLK6, SERPINB12, PNLIPRP3, CASP14, ODZ2, CA2, CRCT1, CWH43 and FLG. Quantitative RT-PCR of conjunctival epithelium samples from 11 patients with SJS and 26 controls showed that the gene expression of PIGR, HEPACAM2 and ADH1C was significantly downregulated while the gene expression of ODZ2 (teneurin-2) was significantly upregulated in patients with SJS. We document that teneurin-2 protein can be expressed in human conjunctival epithelium.ConclusionOur results suggest that the downregulation of PIGR, HEPACAM2 and ADH1C and upregulation of teneurin-2 expression contribute to the pathology of the ocular surface in patients with SJS in the chronic stage.

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Difference in the plasma level of miR‐628‐3p in atopic dermatitis patients with/without atopic keratoconjunctivitis

Ueta

Nishigaki

Komai

et al. 2021

Immunity Inflam & Disease

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Introduction: Some but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We hypothesized that different factors are involved in the severity of ACD and AD. Recently we reported that hsa-miR-628-3p could affect the balance of innate immunity by suppressing pathogen-associated molecular patterns such as toll-like receptor 3 (TLR3), RIG-I, and MDA-5. We also reported that TLR3 positively regulates ocular surface-and skin inflammation such as contact dermatitis and AD.Here we compared the plasma level of miR-628-3p in AD patients with severe AKC with giant papillae and/or shield ulcers, with the level in healthy controls and AD patient without AKC or with very mild AKC. Methods: We used the plasma from 32 AD patients with severe AKC, from 40 healthy controls, and from 23 AD patient without AKC or with very mild AKC without giant papillae nor shield ulcers. Quantitative microRNA PCR assays were used to measure their plasma level of miR-628-3p.Results: We found that plasma miR-628-3p was upregulated in AD with severe AKC, but not in severe AD without severe AKC, nor in our healthy controls. Conclusion:Our new findings suggest that the plasma miR-628-3p level may represent a marker to predict the presence of severe AKC in AD patients.

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Downregulation of interferon-γ-induced protein 10 in the tears of patients with Stevens-Johnson syndrome with severe ocular complications in the chronic stage

Cited by 19 publications

References 8 publications

Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

Gene expression analysis of conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage

Difference in the plasma level of miR‐628‐3p in atopic dermatitis patients with/without atopic keratoconjunctivitis

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