Possible Involvement of Keratinocyte-Derived Microvesicle Particles in Human Photosensitivity Disorders

Risha Annamraju; Madison S Owens; Anita Thyagarajan; Danielle A Corbin; Catherine M T Sherwin; Jade Bryant; Garrett W Fisher; Winston R Owens; Alycia Ketter; Craig A Rohan; Michael G Kemp; Robyn K Crow; Jeffrey B Travers

doi:10.1101/2025.09.24.25336388

Possible Involvement of Keratinocyte-Derived Microvesicle Particles in Human Photosensitivity Disorders

Risha Annamraju, Madison S Owens, Anita Thyagarajan, Danielle A Corbin, Catherine M T Sherwin, Jade Bryant, Garrett W Fisher, Winston R Owens, Alycia Ketter, Craig A Rohan, Michael G Kemp, Robyn K Crow, Jeffrey B Travers

Pediatrics

Research output: Working paper › Preprint

Abstract

BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.

RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients.

CONCLUSION: Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.

Original language	English
Publisher	MedRxiv
DOIs	https://doi.org/10.1101/2025.09.24.25336388
State	Published - Sep 30 2025

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10.1101/2025.09.24.25336388License: CC BY-NC-ND

Possible involvement of keratinocyte-derived microvesicle particles in human photosensitivity disordersSubmitted manuscript, 917 KBLicense: CC BY-NC-ND

Cite this

@techreport{84e30cd4b3ba46f1bd91e05e61660f61,

title = "Possible Involvement of Keratinocyte-Derived Microvesicle Particles in Human Photosensitivity Disorders",

abstract = "BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4\% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients.CONCLUSION: Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.",

author = "Risha Annamraju and Owens, \{Madison S\} and Anita Thyagarajan and Corbin, \{Danielle A\} and Sherwin, \{Catherine M T\} and Jade Bryant and Fisher, \{Garrett W\} and Owens, \{Winston R\} and Alycia Ketter and Rohan, \{Craig A\} and Kemp, \{Michael G\} and Crow, \{Robyn K\} and Travers, \{Jeffrey B\}",

year = "2025",

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doi = "10.1101/2025.09.24.25336388",

language = "English",

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T1 - Possible Involvement of Keratinocyte-Derived Microvesicle Particles in Human Photosensitivity Disorders

AU - Annamraju, Risha

AU - Owens, Madison S

AU - Thyagarajan, Anita

AU - Corbin, Danielle A

AU - Sherwin, Catherine M T

AU - Bryant, Jade

AU - Fisher, Garrett W

AU - Owens, Winston R

AU - Ketter, Alycia

AU - Rohan, Craig A

AU - Kemp, Michael G

AU - Crow, Robyn K

AU - Travers, Jeffrey B

PY - 2025/9/30

Y1 - 2025/9/30

N2 - BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients.CONCLUSION: Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.

AB - BACKGROUND: Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity. Objective: The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.RESULTS: Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients.CONCLUSION: Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.

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