Publications by authors named "Celina Dubin"

7 Publications

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An integrated scalp and blood biomarker approach suggeststhe systemic nature of alopecia areata.

Allergy 2021 Mar 15. Epub 2021 Mar 15.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Alopecia areata (AA) is characterized by immunedysregulation in both scalp and blood, but a largescale approach establishing biomarkersof AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize thetranscriptomicsignature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity.

Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n=18) and healthy individuals (n=8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT).

Results: 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false-discovery-rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp(P<0.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (P<0.05). AA scalp demonstrated significantly greater biomarker dysregulationcompared to blood. An integrated multivariateapproach combining scalp and serum biomarkers improved correlations with disease severity/SALT.

Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.
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http://dx.doi.org/10.1111/all.14814DOI Listing
March 2021

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges.

Ther Clin Risk Manag 2020 31;16:1319-1332. Epub 2020 Dec 31.

Department of Dermatology, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Chronic hand eczema (CHE) is a common and burdensome inflammatory skin condition seen in up to 10% of the population, more often in high-risk occupational workers. Topical therapeutics comprise the standard of care, but up to 65% of cases do not resolve after treatment, and moderate-to-severe cases are often resistant to topical therapeutics and require systemic options instead. To date, there are no systemic therapeutics approved to treat CHE in the United States, but several drugs are under investigation as potential treatments for CHE. The primary focus of this review is on the novel therapeutics, topical and systemic, that are under investigation in recently completed or currently ongoing trials. This review also briefly outlines the existing treatments utilized for CHE, often with limited success or extensive adverse effects. CHE represents a major challenge for physicians and patients alike, and efforts to improve the minimally invasive diagnostic tools and treatment paradigms are ongoing. In the near future, CHE patients may benefit from new topical and systemic therapeutics that specifically target abnormally expressed immune markers.
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http://dx.doi.org/10.2147/TCRM.S292504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780849PMC
December 2020

Objective Evaluation of Skin Sensitivity Across Fitzpatrick Skin Types.

J Drugs Dermatol 2020 Jul;19(7):699-701

Context: Skin sensitivity may be best defined as self-reported intolerance to application of skincare products. It is commonly believed that individuals with darker skin are generally less sensitive, while those lighter skin are more sensitive. However, there is little objective data correlating sensitivity with skin type or with objective measures of sensitivity. Objective: This study assessed Fitzpatrick skin type and self-reported perception of skin sensitivity. Design: A single-blinded, lactic acid sting test was performed on the medial cheeks, where patients were randomized to receive room temperature 10% lactic acid on the left or right cheek with water applied to the contralateral cheek as a control. Outcome Measures: Stinging was assessed 1 minute after application of test solution to one cheek using a visual analogue scale (VAS). Results: There was a statistically significant difference in self-reported skin sensitivity in patients with Fitzpatrick skin types 1-3 vs 4-6 (73.6% vs 46.5%; P= 0.006). Patients who had higher perceived sensitivity were more likely to have objectively measured sensitivity as well, across all skin types (P<0.01). When stratified by skin type, a numerically higher percentage of subjects with Fitzpatrick skin types 1-3 experienced objective sensitivity compared to subjects with skin types 4-6 (45.6% vs 27.9; P=0.058). Conclusions: Patients with self-perceived skin sensitivity were more likely to develop objective stinging compared to those who did not report sensitivity. Skin sensitivity can occur across all skin types, and patients should be asked about self-perceptions of sensitivity as it is likely an indicator of true sensitivity. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5880.
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http://dx.doi.org/10.36849/JDD.2020.5880DOI Listing
July 2020

Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation.

J Am Acad Dermatol 2021 Feb 4;84(2):370-380. Epub 2020 May 4.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.

Objective: To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.

Methods: In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).

Results: Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.

Limitations: Our analysis was limited to 350 proteins.

Conclusion: This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.
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http://dx.doi.org/10.1016/j.jaad.2020.04.138DOI Listing
February 2021

Comparing cutaneous molecular improvement with different treatments in atopic dermatitis patients.

J Allergy Clin Immunol 2020 04 16;145(4):1285-1288. Epub 2020 Jan 16.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.01.005DOI Listing
April 2020

Oral Janus kinase/SYK inhibition (ASN002) suppresses inflammation and improves epidermal barrier markers in patients with atopic dermatitis.

J Allergy Clin Immunol 2019 10 26;144(4):1011-1024. Epub 2019 Jul 26.

Department of Dermatology, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Moderate-to-severe atopic dermatitis (AD) has been associated with significant disease burden and systemic abnormalities and often requires systemic treatments. Currently, safe and effective oral systemic treatments for moderate-to-severe AD are not yet available. ASN002 is an oral inhibitor of the Janus kinase/spleen tyrosine kinase signaling pathways, targeting several cytokine axes (T2/T22/T17/T1) and epidermal differentiation.

Objective: We sought to evaluate the effect of ASN002 on the cellular and molecular biomarker profile of patients with moderate-to-severe AD and to correlate changes in biomarkers to improvements in clinical severity measures and pruritus.

Methods: Thirty-six patients with moderate-to-severe AD were randomized to groups with dose escalation of ASN002 (20, 40, and 80 mg) and a placebo group. Skin biopsy specimens were performed at baseline, day 15, and day 29. Gene expression studies were conducted by using microarray and quantitative RT-PCR, and cellular infiltrates and protein expression were studied by using immunohistochemistry.

Results: ASN002 reversed the lesional skin transcriptome toward a nonlesional phenotype. It also rapidly and significantly suppressed key inflammatory pathways implicated in AD pathogenesis, including T2 (IL4 receptor [IL4R], IL13, CCL13/monocyte chemoattractant protein 4, CCL17/thymus and activation-regulated chemokine, CCL18/pulmonary and activation-regulated chemokine, CCL22/macrophage-derived chemokine, and CCL26/eotaxin-3), T17/T22 (lipocalins, PI3/elafin, CCL20, S100A7/S100A8/S100A9, and IL36G/IL36RN), and T1 (IFNG, CXCL9/CXCL11, and MX1) axes and barrier-related measures (filaggrin [FLG] and CLDN23). Significant improvements in AD gene signatures were observed predominantly in the 40- and 80-mg groups. Smaller and largely nonsignificant molecular changes were seen in the 20-mg and placebo groups.

Conclusion: The Janus kinase/spleen tyrosine kinase inhibitor ASN002 significantly suppressed key AD inflammatory pathways, corresponding to clinical response. ASN002 might be an effective novel therapeutic agent for moderate-to-severe AD.
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http://dx.doi.org/10.1016/j.jaci.2019.07.013DOI Listing
October 2019

Major Differences in Expression of Inflammatory Pathways in Skin from Different Body Sites of Healthy Individuals.

J Invest Dermatol 2019 10 3;139(10):2228-2232.e10. Epub 2019 May 3.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.04.008DOI Listing
October 2019