103 results on '"Czarnowicki, T."'
Search Results
2. 777 Heterogeneous il-9 production by circulating skin-tropic and non-tropic memory T cells in atopic dermatitis
- Author
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Garcia-Jiménez, I., San Nicolàs, L. Sans-de, Curto-Barredo, L., Bertolín-Colilla, M., Figueras-Nart, I., bonfill-Ortí, M., Guilabert, A., Ryzhkova, A., Ferran, M., Damiani, G., Czarnowicki, T., Pujol, R., and Santamaria-Babí, L.F.
- Published
- 2024
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3. 224 Comorbidities and healthcare utilization in 4,197 patients with prurigo nodularis: A cross-sectional population-based analysis
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Czarnowicki, T., Valdman-Grinshpoun, Y., Zaga, A., Cohen, A.D., and Schonmann, Y.
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- 2024
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4. Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin‐homing and systemic T‐cell populations
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Czarnowicki, T., He, H. Y., Wen, H.‐C., Hashim, P. W., Nia, J. K., Malik, K., Estrada, Y., Kimmel, G. W., Taliercio, M., Krueger, J. G., and Guttman‐Yassky, E.
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- 2018
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5. Circulating CLA+ T cells in atopic dermatitis and their possible role as peripheral biomarkers
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Czarnowicki, T., Santamaria‐Babí, L. F., and Guttman‐Yassky, E.
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- 2017
- Full Text
- View/download PDF
6. SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis
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Harari, M., Dreiher, J., Czarnowicki, T., Ruzicka, T., and Ingber, A.
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- 2012
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7. Patients with early-onset psoriasis achieve better results following Dead Sea climatotherapy
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Harari, M., Czarnowicki, T., Fluss, R., Ruzicka, T., and Ingber, A.
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- 2012
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8. Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients
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Czarnowicki, T., Harari, M., Ruzicka, T., and Ingber, A.
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- 2011
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9. 074 Evolution of pathologic T-cell subsets in atopic dermatitis from infancy to adulthood
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Czarnowicki, T., primary, He, H., additional, Kim, H., additional, Kameyama, N., additional, Han, J., additional, Pavel, A.B., additional, Krueger, J.G., additional, Paller, A.S., additional, and Guttman-Yassky, E., additional
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- 2019
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10. 701 High dimensional peripheral blood immune cell profiling of atopic dermatitis patients unveiled IL21 cytokine activation
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Kim, H., primary, Kameyama, N., additional, Glickman, J., additional, He, H., additional, Czarnowicki, T., additional, Pavel, A.B., additional, Estrada, Y., additional, Gonzalez, J., additional, Lee, B., additional, Rahman, A., additional, Merad, M., additional, Krueger, J.G., additional, and Guttman-Yassky, E., additional
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- 2019
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11. 040 Th/Tc9 and Th/Tc17 pathways are augmented in moderate-to-extensive bullous pemphigoid patients and suppressed by bertilimumab
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Kameyama, N., primary, He, H., additional, Kim, H., additional, Czarnowicki, T., additional, Pavel, A.B., additional, Estrada, Y., additional, Gonzalez, J., additional, Fiorino, A.S., additional, Kolatch, B., additional, Sinha, A.A., additional, Seiffert-Sinha, K., additional, Krueger, J.G., additional, and Guttman-Yassky, E., additional
- Published
- 2019
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12. 555 Integrating serum and skin biomarkers to assess disease extent beyond clinical scores, advancing precision therapeutics
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Malik, K., primary, Czarnowicki, T., additional, Wen, H., additional, Noda, S., additional, Pavel, A.B., additional, Nakajima, S., additional, Honda, T., additional, Shin, J.U., additional, Lee, H., additional, Krueger, J.G., additional, Lee, K., additional, Kabashima, K., additional, and Guttman-Yassky, E., additional
- Published
- 2018
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13. 052 Vitiligo is characterized by multi-axis T-cell activation in blood
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Czarnowicki, T., primary, Krueger, J.G., additional, Lebwohl, M., additional, and Guttman-Yassky, E., additional
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- 2018
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14. Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations
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Czarnowicki, T., primary, He, H. Y., additional, Wen, H.-C., additional, Hashim, P. W., additional, Nia, J. K., additional, Malik, K., additional, Estrada, Y., additional, Kimmel, G. W., additional, Taliercio, M., additional, Krueger, J. G., additional, and Guttman-Yassky, E., additional
- Published
- 2017
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15. 642 The serum proteomic signature of pediatric AD suggests early Th2/Th17 skewing and an inverse correlation of disease severity with Th1 markers
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Brunner, P.M., primary, He, H., additional, Czarnowicki, T., additional, Huynh, T., additional, Mueller, K.A., additional, Doytcheva, K., additional, Suarez-Farinas, M., additional, Krueger, J.G., additional, Paller, A.S., additional, and Guttman-Yassky, E., additional
- Published
- 2017
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16. 073 Th17 and Th22 polarization in ichthyosis blood correlates with disease severity and highlights its systemic nature
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Czarnowicki, T., primary, Huynh, T., additional, Itan, Y., additional, Ibler, E., additional, Tran, G., additional, Krueger, J.G., additional, Guttman-Yassky, E., additional, and Paller, A.S., additional
- Published
- 2017
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17. Circulating CLA+T cells in atopic dermatitis and their possible role as peripheral biomarkers
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Czarnowicki, T., primary, Santamaria-Babí, L. F., additional, and Guttman-Yassky, E., additional
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- 2016
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18. 039 Early onset pediatric atopic dermatitis skin phenotype is Th2, but also Th17-polarized
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Esaki, H., primary, Brunner, P.M., additional, Czarnowicki, T., additional, Rodriguez, G., additional, Immaneni, S., additional, Renert-Yuval, Y., additional, Suarez-Farinas, M., additional, Krueger, J.G., additional, Paller, A.S., additional, and Guttman-Yassky, E., additional
- Published
- 2016
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19. 466 Early pediatric atopic dermatitis is a T-cell driven disease accompanied by a secondary B-cell activation
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Czarnowicki, T., primary, Esaki, H., additional, Brunner, P.M., additional, Gonzalez, J., additional, Talasila, S., additional, Berry, A., additional, Gray, J., additional, Krueger, J.G., additional, Guttman-Yassky, E., additional, and Paller, A.S., additional
- Published
- 2016
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20. Circulating CLA+ T cells in atopic dermatitis and their possible role as peripheral biomarkers.
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Czarnowicki, T., Santamaria‐Babí, L. F., and Guttman‐Yassky, E.
- Subjects
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ATOPIC dermatitis treatment , *ATOPIC dermatitis , *T cells , *SKIN biopsy , *BIOMARKERS , *DIAGNOSIS , *PHYSIOLOGY - Abstract
Cutaneous lymphocyte-associated antigen ( CLA+) T cells are specialized for skin homing and represent the main T-cell population in atopic dermatitis ( AD) lesions. CLA+ is expressed on the surface of circulating CD45 RO+ memory T cells and most skin-infiltrating T cells. Mechanistic studies and thus treatment advancements are limited by the need of large number of skin biopsies. Circulating CLA+ T cells may be a reliable surrogate marker of the inflammatory events occurring in the skin, and thus, the evaluation of CLA+ T cells in the blood may eliminate the need for skin biopsies. Preliminary work in AD has established that disease-associated T-cell abnormalities can be approached by either a study of skin lesions or activated CLA+ T-cell subsets in peripheral blood. Future studies in adults and children, across different skin disorders, correlating blood and skin phenotypes and determining skin-homing T-cell functional properties are needed to establish whether CLA+ memory subsets can be used as biomarkers and a substitute for skin biopsies. This review summarizes the latest advancements reached on circulating CLA+ in AD and the great potential they harbor in understanding AD mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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21. SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis
- Author
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Harari, M., primary, Dreiher, J., additional, Czarnowicki, T., additional, Ruzicka, T., additional, and Ingber, A., additional
- Published
- 2011
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- View/download PDF
22. Patients with early‐onset psoriasis achieve better results following Dead Sea climatotherapy
- Author
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Harari, M., primary, Czarnowicki, T., additional, Fluss, R., additional, Ruzicka, T., additional, and Ingber, A., additional
- Published
- 2011
- Full Text
- View/download PDF
23. Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients
- Author
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Czarnowicki, T., primary, Harari, M., additional, Ruzicka, T., additional, and Ingber, A., additional
- Published
- 2010
- Full Text
- View/download PDF
24. P59 The impact of close surveillance on pregnancy outcome among women with a prior history of antepartum complications attributed to thrombosis: a cohort study
- Author
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Salim, R., primary, Czarnowicki, T., additional, Nachum, Z., additional, and Shalev, E., additional
- Published
- 2009
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25. Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood.
- Author
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Czarnowicki T, David E, Yamamura K, Han J, He H, Pavel AB, Glickman J, Erickson T, Estrada Y, Krueger JG, Rangel SM, Paller AS, and Guttman-Yassky E
- Subjects
- Humans, Adolescent, Child, Male, Infant, Female, Child, Preschool, Adult, Infant, Newborn, Young Adult, Case-Control Studies, Immunophenotyping, Severity of Illness Index, Age Factors, Flow Cytometry, Dermatitis, Atopic immunology, Dermatitis, Atopic blood, B-Lymphocyte Subsets immunology, B-Lymphocyte Subsets metabolism, Immunoglobulin E blood, Immunoglobulin E immunology
- Abstract
Background: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined., Objective: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls., Methods: Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®., Results: Adolescents with AD had lower frequencies of major B-cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r = .41, p = .0005). AD severity positively correlated with a list of B-cell subsets (p < .05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls., Conclusions: Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2024
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26. Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.
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García-Jiménez I, Sans-de San Nicolás L, Curto-Barredo L, Bertolín-Colilla M, Sensada-López E, Figueras-Nart I, Bonfill-Ortí M, Guilabert-Vidal A, Ryzhkova A, Ferran M, Damiani G, Czarnowicki T, Pujol RM, and Santamaria-Babí LF
- Subjects
- Humans, Female, Male, Adult, Skin immunology, Skin metabolism, Pyroglyphidae immunology, Animals, Immunoglobulin E immunology, Immunoglobulin E blood, Middle Aged, Antigens, Differentiation, T-Lymphocyte metabolism, Young Adult, Allergens immunology, Adolescent, Membrane Glycoproteins, Dermatitis, Atopic immunology, Dermatitis, Atopic metabolism, Interleukin-9 metabolism, Enterotoxins immunology, Memory T Cells immunology, Memory T Cells metabolism
- Abstract
Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA
+ and extracutaneous/systemic CLA- memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA+ and CLA- T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.- Published
- 2024
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27. Association Between Pruritus and Fibromyalgia: Results of a Population-Based, Cross-Sectional Study.
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Aronov M, Valdman-Grinshpoun Y, Cohen AD, Freud T, and Czarnowicki T
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- Humans, Cross-Sectional Studies, Retrospective Studies, Female, Male, Middle Aged, Adult, Aged, Fibromyalgia epidemiology, Fibromyalgia complications, Pruritus etiology, Pruritus epidemiology
- Abstract
Fibromyalgia is a common musculoskeletal condition that affects up to 3% of the worldwide population. Its pathogenesis is not entirely clear but is thought to involve neurogenic inflammation as well as aberrations in peripheral nerves and central pain mechanisms. It is believed that the same mechanism that causes hypersensitivity and pain in patients with fibromyalgia also predisposes them to pruritus. This population-based, retrospective, cross-sectional study was performed using a computerized database encompassing more than 4.5 million patients to examine the association between fibromyalgia and pruritus as well as pruritus-related skin conditions.
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- 2024
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28. High socioeconomic status is significantly associated with psoriasis: results from a cross-sectional, population-based study of 129,855 patients.
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Dagan O, Schonmann Y, Shavit E, Cohen AD, Valdman-Grinshpoun Y, and Czarnowicki T
- Abstract
Background: While the contribution of environmental factors including smoking, overweight and stress has been validated, data mining for the association between socioeconomic status (SES) and psoriasis prevalence has yielded contradicting observations., Objective: To evaluate the association between psoriasis prevalence and SES., Methods: This was a nationwide population-based cross-sectional retrospective study that included all patients insured by the "Clalit" Health Services (N=4,604,994). Univariable and multivariable logistic regression analyses were conducted to explore the association between psoriasis and SES while controlling for potential sociodemographic and clinical confounders., Results: The study population included 129,855 patients with psoriasis and 4,475,139 individuals without psoriasis. Higher SES was associated with an increased prevalence of psoriasis; in a fully adjusted model, Clalit members within the highest SES were 1.43-fold more likely to have psoriasis (95% CI, 1.39-1.48; P< 0.001), and those at medium SES were 1.2-fold more likely to have psoriasis, compared to those at the lowest SES group (95% CI, 1.18-1.26; P< 0.001; P for linear trend <0.001)., Conclusions: Positive correlation was found between SES and psoriasis prevalence. Further investigation is warranted to elucidate the factors accounting for this observation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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29. CLA+ memory T cells in atopic dermatitis
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Nicolàs LSS, Czarnowicki T, Akdis M, Pujol RM, Lozano-Ojalvo D, Leung DYM, Guttman-Yassky E, and Santamaria-Babí LF
- Subjects
- Humans, Memory T Cells, T-Lymphocyte Subsets, Antigens, Differentiation, T-Lymphocyte, Membrane Glycoproteins, Receptors, Lymphocyte Homing, Skin pathology, Pruritus, Antigens, Neoplasm, Dermatitis, Atopic
- Abstract
Circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)
+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)- Published
- 2024
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30. The pathogenetic role of Th17 immune response in atopic dermatitis.
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David E and Czarnowicki T
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- Humans, Child, Interleukin-17, Skin, Cytokines, Immunity, Dermatitis, Atopic drug therapy
- Abstract
Purpose of Review: As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment., Recent Findings: IL-17 has a dual role of pro-inflammatory and immune protective function, making it an important player in several autoimmune and inflammatory conditions. The extent of IL-17 axis involvement in AD pathogenesis is still debatable. Emerging data show that Th17-related cytokines/chemokines are elevated in skin and sera samples of AD patients, with some articles reporting correlations with disease severity. Particularly increased Th17 signature in specific AD patient subsets, such as Asian-origin or pediatric patients, suggests that certain patients' disease presentations are more predominantly influenced by Th17, and, thus, they may benefit more from Th17 therapeutic targeting approaches. Lack of clinical efficacy with anti-Th17 biologics in AD patients, underscores the need to better elucidate the role of Th17 in AD pathogenesis, along with its utility in therapy., Summary: The well established role of IL-17 in autoimmune disorders hints for its possible participation in AD disease pathogenesis. Subsequent investigations are needed to assess whether the targeting of specific IL-17 isoforms, homodimers, or heterodimers in specific subpopulations of AD can modify treatment outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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31. Chronic Spontaneous Urticaria in Patients With Interstitial Cystitis/Bladder Pain Syndrome: Insights From Big Data Analyses.
- Author
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Anis O, Kridin K, Cohen AD, Levmore M, Yaron S, Valdman-Grinshpoun Y, and Czarnowicki T
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- Humans, Female, Middle Aged, Retrospective Studies, Cross-Sectional Studies, Logistic Models, Cystitis, Interstitial complications, Cystitis, Interstitial epidemiology, Cystitis, Interstitial diagnosis, Chronic Urticaria complications
- Abstract
Objective: To examine the association between chronic spontaneous urticaria (CSU) and interstitial cystitis/bladder pain syndrome (IC/BPS)., Methods: A population-based retrospective cross-sectional study was performed using the Clalit Health Services medical database. The prevalence of CSU was compared between patients diagnosed with IC/BPS and age- and gender-matched controls. Univariate analysis was performed using Chi-square and Student t test and a multivariable analysis was performed using a logistic regression model., Results: The study included 681 patients with IC/BPS and 3376 demographically matched controls. The mean age of IC/BPS patients was 60 years old. The prevalence of CSU among patients with IC/BPS was higher as compared to the control group (20% vs 13.7%; P <.001). The adjusted OR for CSU in patients with IC/BPS was 1.58 (95% CI 1.28-1.97). Female gender and Jewish ethnicity were associated with the coexistence of these disorders (OR 1.7 95% CI 1.36-2.13, and 1.6 95% CI 1.28-2, respectively)., Conclusion: A significant association was found between IC/BPS and CSU. This finding may support the presence of allergic/immune components in the pathogenesis of IC/BPS., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2023
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32. High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.
- Author
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Czarnowicki T, Kim HJ, Villani AP, Glickman J, Duca ED, Han J, Pavel AB, Lee BH, Rahman AH, Merad M, Krueger JG, and Guttman-Yassky E
- Subjects
- Cytokines, Humans, Interleukin-13, Skin, Dermatitis, Atopic immunology, Interleukins immunology, T-Lymphocyte Subsets cytology
- Abstract
Background: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL-21 may be involved in inflammatory skin diseases but its role in AD is not well established., Methods: We studied T-cell polarization in the blood of 20 moderate-to-severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4
+ /CD8+ T-cell subsets. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to analyze skin samples., Results: Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T-cell metaclusters. A CD4+ skin-homing IL-13+ monocytokine and a novel IL-13+ IL-21+ multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL-13 signature characterized both clusters, levels were significantly higher in the IL-21+ group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL-21 counts and colocalization with IL-13/IL-4R in AD skin., Conclusion: A multicytokine signature characterizes moderate-to-severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL-21 signature in blood and skin hints for a potential pathogenic role of IL-21 in AD., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)- Published
- 2021
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33. The erythema Q-score, an imaging biomarker for redness in skin inflammation.
- Author
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Frew J, Penzi L, Suarez-Farinas M, Garcet S, Brunner PM, Czarnowicki T, Kim J, Bottomley C, Finney R, Cueto I, Fuentes-Duculan J, Ohmatsu H, Lentini T, Yanofsky V, Krueger JG, Guttman-Yassky E, and Gareau D
- Subjects
- Biomarkers, Color, Humans, Observer Variation, Patch Tests, Photography, Reproducibility of Results, Skin diagnostic imaging, Skin Pigmentation, Algorithms, Dermatitis diagnostic imaging, Erythema diagnostic imaging, Image Processing, Computer-Assisted, Severity of Illness Index
- Abstract
Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with inter-rater reliability and variability in the setting of higher Fitzpatrick skin types make visual erythema assessment unreliable. We developed and validated a computer-assisted image-processing algorithm (EQscore) to reliably quantify erythema (across a range of skin types) in the dermatology clinical setting. Our image processing algorithm evaluated erythema based upon green light suppression differentials between affected and unaffected skin. A group of four dermatologists used a 4-point Likert scale as a human evaluation of similar erythematous patch tests. The algorithm and dermatologist scores were compared across 164 positive patch test reactions. The intra-class correlation coefficient of groups and the correlation coefficient between groups were calculated. The EQscore was validated on and independent image set of psoriasis, minimal erythema dose testing and steroid-induced blanching images. The reliability of the erythema quantification method produced an intra-class correlation coefficient of 0.84 for the algorithm and 0.67 for dermatologists. The correlation coefficient between groups was 0.85. The EQscore demonstrated high agreement with clinical scoring and superior reliability compared with clinical scoring, avoiding the pitfalls of erythema underrating in the setting of pigmentation. The EQscore is easily accessible (http://lab.rockefeller.edu/krueger/EQscore), user-friendly, and may allow dermatologists to more readily and accurately rate the severity of dermatological conditions and the response to therapeutic treatments., (© 2020 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
- Published
- 2021
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34. Apremilast and systemic retinoid combination treatment for moderate to severe palmoplantar psoriasis.
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Czarnowicki T, Rosendorff BP, and Lebwohl MG
- Subjects
- Drug Therapy, Combination, Humans, Male, Middle Aged, Psoriasis pathology, Severity of Illness Index, Thalidomide administration & dosage, Treatment Outcome, Dermatologic Agents administration & dosage, Psoriasis drug therapy, Retinoids administration & dosage, Thalidomide analogs & derivatives
- Published
- 2020
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35. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood.
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Czarnowicki T, He H, Canter T, Han J, Lefferdink R, Erickson T, Rangel S, Kameyama N, Kim HJ, Pavel AB, Estrada Y, Krueger JG, Paller AS, and Guttman-Yassky E
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Dermatitis, Atopic pathology, Female, Humans, Infant, Infant, Newborn, Male, Th1 Cells pathology, Th2 Cells pathology, Cytokines immunology, Dermatitis, Atopic immunology, HLA-DR Antigens immunology, Th1 Cells immunology, Th2 Cells immunology
- Abstract
Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored., Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects., Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4
+ /CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA- T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies., Results: Although CLA+ TH 1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ TH 2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA- TH 2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22)., Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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36. The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.
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Brunner PM, He H, Pavel AB, Czarnowicki T, Lefferdink R, Erickson T, Canter T, Puar N, Rangel SM, Malik K, Estrada Y, Krueger JG, Guttman-Yassky E, and Paller AS
- Subjects
- Age Factors, Biomarkers blood, Case-Control Studies, Child, Preschool, Chronic Disease, Dermatitis, Atopic metabolism, E-Selectin blood, Fatty Acid-Binding Proteins blood, Female, Fibroblast Growth Factors blood, Humans, Infant, Interleukin-2 Receptor alpha Subunit blood, Male, Peroxidase blood, Proteome metabolism, RNA, Messenger metabolism, Severity of Illness Index, Transforming Growth Factor alpha blood, Chemokines blood, Dermatitis, Atopic blood, Elafin blood, Inflammation blood, Matrix Metalloproteinases blood, Receptors, Interleukin blood
- Abstract
Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD., Objective: To analyze blood inflammatory proteins of early pediatric AD., Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD., Results: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11)., Limitations: Different baseline expression levels in healthy pediatric vs adult samples., Conclusions: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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37. Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.
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Czarnowicki T, He H, Leonard A, Kim HJ, Kameyama N, Pavel AB, Li R, Estrada Y, Wen HC, Kimmel GW, Kim HJ, Chima M, Lebwohl M, Krueger JG, and Guttman-Yassky E
- Subjects
- Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Disease Progression, Female, Flow Cytometry, Humans, Inflammation, Male, Middle Aged, Oligosaccharides metabolism, Sialyl Lewis X Antigen analogs & derivatives, Sialyl Lewis X Antigen metabolism, Th2 Cells immunology, Alopecia Areata diagnosis, Biomarkers blood, Cytokines blood, Dermatitis, Atopic diagnosis, Skin immunology, Th1 Cells immunology, Vitiligo diagnosis
- Abstract
Background: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA)
+ T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo., Objective: We sought to measure cytokine production by circulating skin-homing (CLA+ ) versus systemic (CLA- ) "polar" CD4+ /CD8+ ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects., Methods: Flow cytometry was used to measure levels of the cytokines IFN-γ, IL-13, IL-9, IL-17, and IL-22 in CD4+ /CD8+ T cells in the blood of 19 patients with moderate-to-severe nonsegmental/generalized vitiligo, moderate-to-severe AA (n = 32), psoriasis (n = 24), or AD (n = 43) and control subjects (n = 30). Unsupervised clustering differentiated subjects into groups based on cellular frequencies., Results: Patients with Vitiligo showed the highest CLA+ /CLA- TH 1/type 1 cytotoxic T-cell polarization, with parallel TH 2/TH 9/TH 17/TH 22 level increases to levels often greater than those seen in patients with AA, AD, or psoriasis (P < .05). Total regulatory T-cell counts were lower in patients with vitiligo than in control subjects and patients with AD or psoriasis (P < .001). Vitiligo severity correlated with levels of multiple cytokines (P < .1), whereas duration was linked with IFN-γ and IL-17 levels (P < .04). Patients and control subjects grouped into separate clusters based on blood biomarkers., Conclusions: Vitiligo is characterized by a multicytokine polarization among circulating skin-homing and systemic subsets, which differentiates it from other inflammatory/autoimmune skin diseases. Future targeted therapies should delineate the relative contribution of each cytokine axis to disease perpetuation., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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38. Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients.
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Brunner PM, Israel A, Leonard A, Pavel AB, Kim HJ, Zhang N, Czarnowicki T, Patel K, Murphrey M, Ramsey K, Rangel S, Zebda R, Soundararajan V, Zheng X, Estrada YD, Xu H, Krueger JG, Paller AS, and Guttman-Yassky E
- Subjects
- Age of Onset, Biomarkers analysis, Biopsy, Child, Preschool, Dermatitis, Atopic blood, Female, Gene Expression Profiling, Humans, Infant, Leukocytes, Mononuclear metabolism, Male, Dermatitis, Atopic genetics, Skin metabolism, Transcriptome
- Abstract
Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature., Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD., Methods: We compared microarrays and reverse transcription polymerase chain reaction (RT-PCR) of blood cells from 28 AD children (<5 years and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes (DEGs) in blood (fold change [FCH] > 1.2 and false discovery rate [FDR] < 0.05) were then compared with skin DEGs., Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were up-regulated in early pediatric AD blood, whereas IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss [TEWL]), whereas Th2/Th17-induced interleukin (IL)-19 was positively correlated with SCORAD. Although a few RT-PCR-defined immune markers (IL-13/CCL22) were increased in blood, as previously also reported for skin, minimal overlap based on gene array DEGs was seen., Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile; however, markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course, allergic comorbidity development, and response to systemic medications., (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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39. Ichthyosis molecular fingerprinting shows profound T H 17 skewing and a unique barrier genomic signature.
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Malik K, He H, Huynh TN, Tran G, Mueller K, Doytcheva K, Renert-Yuval Y, Czarnowicki T, Magidi S, Chou M, Estrada YD, Wen HC, Peng X, Xu H, Zheng X, Krueger JG, Paller AS, and Guttman-Yassky E
- Subjects
- Adolescent, Adult, Aged, Child, DNA Fingerprinting, Female, Filaggrin Proteins, Genome, Humans, Ichthyosis genetics, Interleukin-1 genetics, Interleukin-17 genetics, Lipid Metabolism genetics, Lymphocyte Activation, Male, Microarray Analysis, Middle Aged, Netherton Syndrome genetics, Transcriptome, Young Adult, Ichthyosis immunology, Netherton Syndrome immunology, T-Lymphocytes immunology, Th17 Cells immunology, Tight Junctions genetics
- Abstract
Background: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy., Objective: We sought to profile the molecular fingerprint of the most common orphan ichthyoses., Methods: Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16)., Results: Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T
H 1/IFN-γ, OASL, and TH 2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05). Ichthyoses lacked the epidermal differentiation and tight junction alterations of patients with AD (loricrin, filaggrin, and claudin 1) but showed characteristic alterations in lipid metabolism genes (ELOVL fatty acid elongase 3 and galanin), with parallel reductions in extracellular lipids and corneocyte compaction in all ichthyoses except epidermolytic ichthyosis, suggesting phenotypic variations. Transepidermal water loss, a functional barrier measure, significantly correlated with IL-17-regulated gene expression (IL17F and IL36A/IL36B/IL36G)., Conclusion: Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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40. Atopic dermatitis endotypes and implications for targeted therapeutics.
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Czarnowicki T, He H, Krueger JG, and Guttman-Yassky E
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Female, Filaggrin Proteins, Humans, Infant, Infant, Newborn, Male, Cytokines genetics, Cytokines immunology, Dermatitis, Atopic classification, Dermatitis, Atopic ethnology, Dermatitis, Atopic genetics, Dermatitis, Atopic therapy, Immunoglobulin E genetics, Immunoglobulin E immunology, Intermediate Filament Proteins genetics, Intermediate Filament Proteins immunology, Mutation, Precision Medicine
- Abstract
Recent research advancements indicate that atopic dermatitis (AD) is a complex disease characterized by different subtypes/phenotypes based on age, disease chronicity, ethnicity, filaggrin and IgE status, and underlying molecular mechanisms/endotypes. This heterogeneity advocates against the traditional "one-size-fits-all" therapeutic approaches still used to manage AD. Precision medicine approaches, striving for targeted, tailored, endotype-driven disease prevention and treatment, rely on detailed definitions of the disease's variability across different phenotypes. Studies have shown that AD harbors different endotypes across different age groups and ethnicities and according to IgE levels and filaggrin mutation status. These include European American versus Asian patients, children versus adults, intrinsic versus extrinsic (IgE status) disease, and patients with and without filaggrin mutations. Therapies targeting different cytokine axes and other mechanisms involved in disease pathogenesis, which are currently being tested for patients with AD across the disease spectrum, will expand our ability to dissect the relative contribution of each of these pathways to disease perpetuation., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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41. The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.
- Author
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Czarnowicki T, He H, Leonard A, Malik K, Magidi S, Rangel S, Patel K, Ramsey K, Murphrey M, Song T, Estrada Y, Wen HC, Krueger JG, Guttman-Yassky E, and Paller AS
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antigens, Differentiation, T-Lymphocyte blood, Biomarkers blood, Child, Child, Preschool, Female, Flow Cytometry, Humans, Ichthyosis blood, Ichthyosis pathology, Immunohistochemistry, Infant, Male, Middle Aged, Th17 Cells metabolism, Young Adult, Cytokines blood, Ichthyosis immunology, Lymphocyte Activation immunology, Th17 Cells immunology
- Abstract
The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4
+ /CD8+ and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ /CD8+ T cells, with inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell activation, respectively. We compared peripheral blood from 47 patients with ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical measures included the ichthyosis severity score, with subsets for erythema and scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive inducible co-stimulator molecule activation (P < 0.001), particularly epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22-producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper 2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-γ frequencies (P > 0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with clinical measures, whereas IFN-γ clustered with age. Our data show peripheral blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical measures. Targeted therapies should dissect the relative contribution of polar cytokines to disease pathogenesis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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42. Serum from Asian patients with atopic dermatitis is characterized by T H 2/T H 22 activation, which is highly correlated with nonlesional skin measures.
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Wen HC, Czarnowicki T, Noda S, Malik K, Pavel AB, Nakajima S, Honda T, Shin JU, Lee H, Chou M, Estrada Y, Zheng X, Xu H, Krueger JG, Lee KH, Kabashima K, and Guttman-Yassky E
- Subjects
- Adult, Asian People, Dermatitis, Atopic immunology, Female, Humans, Male, Young Adult, Biomarkers blood, Dermatitis, Atopic blood, Lymphocyte Activation immunology, Lymphocyte Subsets immunology, Th2 Cells immunology
- Published
- 2018
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43. Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.
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Czarnowicki T, Dohlman AB, Malik K, Antonini D, Bissonnette R, Chan TC, Zhou L, Wen HC, Estrada Y, Xu H, Bryson C, Shen J, Lala D, Ma'ayan A, McGeehan G, Gregg R, and Guttman-Yassky E
- Subjects
- ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters immunology, Administration, Cutaneous, Adult, Biological Transport drug effects, Biological Transport immunology, Dermatitis, Atopic genetics, Dermatitis, Atopic immunology, Dermatitis, Atopic pathology, Double-Blind Method, Epidermis immunology, Epidermis pathology, Female, Filaggrin Proteins, Gene Expression Regulation immunology, Humans, Interleukin-6 genetics, Interleukin-6 immunology, Intermediate Filament Proteins genetics, Intermediate Filament Proteins immunology, Keratin-16 genetics, Keratin-16 immunology, Liver X Receptors genetics, Liver X Receptors immunology, Male, Membrane Proteins genetics, Membrane Proteins immunology, Middle Aged, RNA, Messenger genetics, RNA, Messenger immunology, S100A12 Protein genetics, S100A12 Protein immunology, Severity of Illness Index, Sterol Regulatory Element Binding Protein 1 genetics, Sterol Regulatory Element Binding Protein 1 immunology, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Dermatitis, Atopic drug therapy, Epidermis drug effects, Immunologic Factors therapeutic use, Liver X Receptors agonists, RNA, Messenger agonists
- Abstract
Background: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems., Objective: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD)., Methods: A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated., Results: Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid (adenosine triphosphate-binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, P < .01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several T
H 17/TH 22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers., Conclusion: Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities., Trial Registration: clinicaltrials.gov Identifier: NCT02655679., (Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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44. The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab.
- Author
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Paller AS, Czarnowicki T, Renert-Yuval Y, Holland K, Huynh T, Sadlier M, McAleer MA, Tran G, Geddes GC, Irvine AD, and Guttman-Yassky E
- Subjects
- Cardiomyopathies genetics, Child, Dermatitis genetics, Dermatitis, Exfoliative genetics, Female, Genotype, Humans, Hypersensitivity genetics, Ichthyosis immunology, Immunophenotyping, Male, Mutation, Syndrome, Th1 Cells, Th17 Cells, Dermatologic Agents therapeutic use, Desmoplakins genetics, Ichthyosis drug therapy, Ichthyosis genetics, Ustekinumab therapeutic use
- Abstract
Background: The immune abnormalities underlying the ichthyoses are poorly understood., Objective: To determine the immunophenotype of an ichthyosis resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin gene (DSP) and target therapy on the basis of molecular pathogenesis., Methods: Immunophenotyping was performed by using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy., Results: On the basis of the discovery of T helper 1 and T helper 17/interleukin 23 skewing in the skin and T helper 17/interleukin 22 skewing in blood, ustekinumab therapy was initiated. Ustekinumab was also administered to a boy with an SR6 region DSP mutation and ichthyosis without cardiomyopathy. Both children responded despite previous poor responses to immunosuppressants and retinoids., Limitations: Small number of patients and immunophenotyping in only 1 patient., Conclusion: An understanding of the molecular basis of inflammation in rare cutaneous disorders can lead to targeted therapy, which promises to be more beneficial than broad immunosuppressants., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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45. An Update on the Pathophysiology of Atopic Dermatitis.
- Author
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Malik K, Heitmiller KD, and Czarnowicki T
- Subjects
- Dendritic Cells immunology, Dermatitis, Atopic immunology, Environmental Exposure adverse effects, Humans, Immunity, Innate, Microbiota, Skin microbiology, T-Lymphocytes, Regulatory immunology, Adaptive Immunity, Dermatitis, Atopic etiology, Dermatitis, Atopic physiopathology, Skin Physiological Phenomena, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Atopic dermatitis (AD) is increasingly recognized as a complex, inflammatory skin disease involving interplay of multiple elements. This article notes key advances in understanding of immune dysregulation, skin barrier dysfunction, environmental, genetic, and microbial influences orchestrating disease pathogenesis, and the relevance of therapeutic interventions in each area. Accumulating evidence and the discovery of new T-cell subsets has matured AD as a multiple-cytokine-axes-driven disorder, evolved from the widely held belief of it being a biphasic Th1/Th2 disease. These new insights have led to active trials testing multiple, targeted therapeutics with better efficacy and safety-profiles., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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46. Alterations in B-cell subsets in pediatric patients with early atopic dermatitis.
- Author
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Czarnowicki T, Esaki H, Gonzalez J, Renert-Yuval Y, Brunner P, Oliva M, Estrada Y, Xu H, Zheng X, Talasila S, Haugh I, Huynh T, Lyon S, Tran G, Sampson H, Suárez-Fariñas M, Krueger JG, Guttman-Yassky E, and Paller AS
- Subjects
- Adult, Aging immunology, Allergens immunology, Child, Preschool, Dermatitis, Atopic blood, Female, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Infant, Male, Middle Aged, Skin cytology, Skin immunology, T-Lymphocytes immunology, B-Lymphocyte Subsets immunology, Dermatitis, Atopic immunology
- Abstract
Background: B cells undergo maturation and class-switching in response to antigen exposure and T-cell help. Early B-cell differentiation has not been defined in patients with early-onset atopic dermatitis (AD)., Objective: We sought to define the frequency of B-cell subsets associated with progressive B-cell maturation and IgE class-switching., Methods: We studied 27 children and 34 adults with moderate-to-severe AD (mean SCORAD score, 55 and 65, respectively) and age-matched control subjects (15 children and 27 adults). IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometric panel were used to determine the frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgE) levels were measured by using ImmunoCAP., Results: Compared with adults, children showed T-cell predominance in the skin. Circulating CD19
+ CD20+ B-cell counts were lower in patients with pediatric AD than in control subjects (24% vs 33%, P = .04), whereas CD3+ T-cell counts were higher (62% vs 52%, P = .05). A decreased B-cell/T-cell lymphocyte ratio with age was observed only in pediatric control subjects (r = -0.48, P = .07). In pediatric patients with AD, a positive correlation was observed between B-cell/T-cell ratio and nonswitched memory B-cell counts (r = 0.42, P = .03). Higher frequencies of positive sIgE levels were seen in pediatric patients with AD (P < .0001). Diverse sIgE levels correlated with SCORAD scores and age of pediatric patients with AD (P < .01). Positive correlations were observed between activated B-cell and memory T-cell counts (P < .02). In patients with AD, IgE sensitization to most allergens clustered with age, TH 1, TH 2, total IgE levels, and B-cell memory subsets., Conclusions: Peripheral B and T cells are altered in pediatric patients with early AD, but T cells predominate in skin lesions., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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47. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march.
- Author
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Czarnowicki T, Krueger JG, and Guttman-Yassky E
- Subjects
- Animals, Antimicrobial Cationic Peptides immunology, Environment, Humans, Skin immunology, Dermatitis, Atopic immunology, Dermatitis, Atopic prevention & control, Dermatitis, Atopic therapy
- Abstract
Skin barrier abnormalities have been suggested to play an essential role in initiation of early atopic dermatitis (AD). Antigen penetration through a compromised barrier likely leads to increased innate immune responses, antigen-presenting cell stimulation, and priming of overt cutaneous disease. In a T
H 2-promoting environment, T-cell/B-cell interactions occurring in regional lymph nodes lead to excessive IgE switch. Concurrent redistribution of memory T cells into the circulation not only leads to exacerbation of AD through T-cell skin infiltration but also spreads beyond the skin to initiate the atopic march, which includes food allergy, asthma, and allergic rhinitis. Possible primary interventions to prevent AD are focusing on improving skin barrier integrity, including supplementing barrier function with moisturizers. As for secondary prophylaxis in children with established AD, this can be stratified into prevention of disease exacerbations by using proactive approaches (with either topical corticosteroids or topical calcineurin inhibitors) in mild AD cases or the prevention of other atopic disorders that will probably mandate systemic immunosuppression in severe AD cases., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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48. Circulating CLA + T cells in atopic dermatitis and their possible role as peripheral biomarkers.
- Author
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Czarnowicki T, Santamaria-Babí LF, and Guttman-Yassky E
- Subjects
- Age Factors, Biomarkers, Dermatitis, Atopic blood, Humans, Immunophenotyping, Lymphocyte Count, Lymphocyte Function-Associated Antigen-1 metabolism, Phenotype, Skin immunology, Skin metabolism, Skin pathology, Antigens, Differentiation, T-Lymphocyte metabolism, Dermatitis, Atopic immunology, Dermatitis, Atopic metabolism, Membrane Glycoproteins metabolism, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism
- Abstract
Cutaneous lymphocyte-associated antigen (CLA
+ ) T cells are specialized for skin homing and represent the main T-cell population in atopic dermatitis (AD) lesions. CLA+ is expressed on the surface of circulating CD45RO+ memory T cells and most skin-infiltrating T cells. Mechanistic studies and thus treatment advancements are limited by the need of large number of skin biopsies. Circulating CLA+ T cells may be a reliable surrogate marker of the inflammatory events occurring in the skin, and thus, the evaluation of CLA+ T cells in the blood may eliminate the need for skin biopsies. Preliminary work in AD has established that disease-associated T-cell abnormalities can be approached by either a study of skin lesions or activated CLA+ T-cell subsets in peripheral blood. Future studies in adults and children, across different skin disorders, correlating blood and skin phenotypes and determining skin-homing T-cell functional properties are needed to establish whether CLA+ memory subsets can be used as biomarkers and a substitute for skin biopsies. This review summarizes the latest advancements reached on circulating CLA+ in AD and the great potential they harbor in understanding AD mechanisms., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2017
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49. Patch testing of food allergens promotes Th17 and Th2 responses with increased IL-33: a pilot study.
- Author
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Ungar B, Correa da Rosa J, Shemer A, Czarnowicki T, Estrada YD, Fuentes-Duculan J, Xu H, Zheng X, Peng X, Suárez-Fariñas M, Nowak-Wegrzyn A, Sampson HA, Krueger JG, and Guttman-Yassky E
- Subjects
- Adult, Case-Control Studies, Female, Humans, Interleukin-33 metabolism, Male, Middle Aged, Pilot Projects, Th17 Cells physiology, Th2 Cells physiology, Food Hypersensitivity immunology, Patch Tests
- Published
- 2017
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50. Early-onset pediatric atopic dermatitis is T H 2 but also T H 17 polarized in skin.
- Author
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Esaki H, Brunner PM, Renert-Yuval Y, Czarnowicki T, Huynh T, Tran G, Lyon S, Rodriguez G, Immaneni S, Johnson DB, Bauer B, Fuentes-Duculan J, Zheng X, Peng X, Estrada YD, Xu H, de Guzman Strong C, Suárez-Fariñas M, Krueger JG, Paller AS, and Guttman-Yassky E
- Subjects
- Adult, Age Factors, Aged, Child, Preschool, Cytokines metabolism, Dermatitis, Atopic immunology, Eczema immunology, Female, Filaggrin Proteins, Humans, Infant, Male, Middle Aged, Psoriasis immunology, United States, Dermatitis, Atopic pathology, Eczema pathology, Hispanic or Latino, Psoriasis pathology, Skin pathology, Th17 Cells immunology, Th2 Cells immunology
- Abstract
Background: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T
H 2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies., Objective: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD., Methods: Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects., Results: In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3+ , CD11c+ , and FcεRI+ ) than adults with AD. Similar to adults, strong activation of the TH 2 (IL-13, IL-31, and CCL17) and TH 22 (IL-22 and S100As) axes and some TH 1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH 17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH 9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001)., Conclusion: The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess TH 2 activation characterizes both, TH 9 and TH 17 are highly activated at disease initiation. Increases in IL-19 levels might link TH 2 and TH 17 activation., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2016
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