151 results on '"Prinz JC"'
Search Results
2. From bench to bedside – translational research in psoriasis
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Prinz, JC
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- 2010
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3. The role of IL-23 and the IL-23/T(H)17 immune axis in the pathogenesis and treatment of psoriasis
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Girolomoni, G, Strohal, R, Puig, L, Bachelez, H, Barker, J, Boehncke, WH, and Prinz, JC
- Abstract
Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (T(H)17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL-23, a heterodimer composed of a p40 subunit also found in IL-12 and a p19 subunit exclusive to IL-23. IL-23 is important for maintaining T(H)17 responses, and levels of IL-23 are elevated in psoriatic skin compared with non-lesional skin. A number of agents that specifically inhibit IL-23p19 are currently in development for the treatment of moderate-to-severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL-23/T(H)17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways.
- Published
- 2017
4. Treatment of psoriasis with etanercept: the typical patient profile
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Prinz, JC, Puig, L, and Girolomoni, G
- Abstract
The chronic nature of psoriasis means that patients often require lifetime treatment. Over this time, treatment frequently has to be adapted to meet variable demands resulting from changes in life course and life events. Biological drugs used to treat psoriasis vary in their dosing regimens, convenience and flexibility. Dermatologists need to understand which biologic agent is best suited for each individual patient. A wealth of evidence supports the safe and effective use of etanercept, which offers a rapid and sustained response, flexibility of dosing, maintenance of response after dose reduction or interruption, and efficacy against non-skin manifestations such as psoriatic arthritis. An expert panel met to agree the typical patient profile of a psoriasis patient treated with etanercept, the main benefits of etanercept in psoriasis, and the patient group most likely to benefit from its use. They agreed that flexibility of dosing, the potential to individualize therapy by stopping and starting treatment while maintaining efficacy, and the possibility of cost saving through the use of flexible treatment regimens were important benefits supporting the use of etanercept in many patients with psoriasis.
- Published
- 2016
5. Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper
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Girolomoni, G, Griffiths, CEM, Krueger, J, Nestle, FO, Nicolas, JF, Prinz, JC, Puig, L, Stahle, M, van de Kerkhof, PCM, Allez, M, Emery, P, and Paul, C
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early intervention ,psoriasis ,management ,pathophysiology ,Comorbidities - Abstract
Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely clear lesions. Treatment with systemic agents including biologics is often undertaken only when topical agents have proved unsuitable, even in patients with moderate to severe disease. However, there is evidence that in other IMIDs (rheumatoid arthritis and Crohn's disease), targeted systemic treatment given early in the treatment pathway may improve long-term patient outcomes. We hypothesize that a patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway ("early intervention") with the goal of complete clearance, may improve control of cutaneous symptoms and may also modify disease course and burden. Critical points to address when designing an early intervention study would include: the definition of psoriasis disease activity; patient selection; intervention selection; and dosing strategies.
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- 2015
6. [The Nessos shirt: did Herakles die from scleroderma?]
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Prinz, Jc, Schoinas, S, Peris, Ketty, Knauss, Fs, Peris, Ketty (ORCID:0000-0002-5237-0463), Prinz, Jc, Schoinas, S, Peris, Ketty, Knauss, Fs, and Peris, Ketty (ORCID:0000-0002-5237-0463)
- Abstract
N/A
- Published
- 2011
7. Combination of skin, joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial
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Prinz, JC, primary, FitzGerald, O, additional, Boggs, RL, additional, Foehl, J, additional, Robertson, D, additional, Pedersen, R, additional, Molta, CT, additional, and Freundlich, B, additional
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- 2010
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8. Effect of Calcipotriol on Etanercept Partial Responder Psoriasis Vulgaris and Psoriatic Arthritis Patients
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Campione, E, primary, Mazzotta, A, additional, Paternò, EJ, additional, Diluvio, L, additional, Prinz, JC, additional, and Chimenti, S, additional
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- 2009
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9. Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus
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Boehncke, W-H, primary, Brasie, RA, additional, Barker, J, additional, Chimenti, S, additional, Dauden, E, additional, de Rie, M, additional, Dubertret, L, additional, Giannetti, A, additional, Katsambas, A, additional, Kragballe, K, additional, Naeyaert, JM, additional, Ortonne, J-P, additional, Peyri, J, additional, Prinz, JC, additional, Saurat, J-H, additional, Strohal, R, additional, van de Kerkhof, P, additional, and Sterry, W, additional
- Published
- 2006
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10. 0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observer-blinded study
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Ortonne, JP, primary, Van de Kerkhof, PC, additional, Prinz, JC, additional, Bieber, T, additional, Lahfa, M, additional, Rubins, A, additional, Wozel, G, additional, and Lorette, G., additional
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- 2006
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11. Biologics bei Psoriasis
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Prinz, JC, primary
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- 2004
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12. The role of T cells in psoriasis
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Prinz, JC, primary
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- 2003
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13. Book Review
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Prinz, JC, primary
- Published
- 1999
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14. Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): Results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials.
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Lebwohl M, Leonardi C, Griffiths CE, Prinz JC, Szapary PO, Yeilding N, Guzzo C, Li S, Hsu MC, and Strober B
- Published
- 2012
15. 'Borrelia-associated early-onset morphea': a particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies? Results of a cohort analysis and presentation of three cases.
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Prinz JC, Kutasi Z, Weisenseel P, Pótó L, Battyáni Z, and Ruzicka T
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- 2009
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16. Erythema marginatum hemorrhagicum: A unique cutaneous side effect of sorafenib.
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Rübsam K, Flaig MJ, Ruzicka T, and Prinz JC
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- 2011
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17. Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus.
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Torres T, Brembilla NC, Langley RG, Warren RB, Thaçi D, Kolios AGA, Prinz JC, Londono-Garcia A, Nast A, Santin M, Goletti D, Abreu M, Spuls P, Boehncke WH, and Puig L
- Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management., (© 2024 European Academy of Dermatology and Venereology.)
- Published
- 2024
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18. Generalized pustular psoriasis of the 'von Zumbusch'-type: a sepsis mimic with low PCT values.
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Prinz JC and French LE
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- 2024
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19. Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity.
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Ishimoto T, Arakawa Y, Vural S, Stöhr J, Vollmer S, Galinski A, Siewert K, Rühl G, Poluektov Y, Delcommenne M, Horvath O, He M, Summer B, Pohl R, Alharbi R, Dornmair K, Arakawa A, and Prinz JC
- Subjects
- Humans, CD8-Positive T-Lymphocytes, HLA-C Antigens, Autoantigens, Peptides, Receptors, Antigen, T-Cell, ADAMTS Proteins, Autoimmunity, Psoriasis
- Abstract
Introduction: Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8
+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity., Methods: We screened databases with the peptide recognition motif of the Vα3S1/Vβ13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers., Results: We identified peptides from wheat, Saccharomyces cerevisiae , microbiota, tobacco, and pathogens that activated both the Vα3S1/Vβ13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients., Discussion: Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis., Competing Interests: YP and MD are employees of MBL International, Woburn, MA, U.S.A. MBL International may market the tetramers for diagnostic purposes. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Ishimoto, Arakawa, Vural, Stöhr, Vollmer, Galinski, Siewert, Rühl, Poluektov, Delcommenne, Horvath, He, Summer, Pohl, Alharbi, Dornmair, Arakawa and Prinz.)- Published
- 2024
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20. EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.
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Kuiper JJ, Prinz JC, Stratikos E, Kuśnierczyk P, Arakawa A, Springer S, Mintoff D, Padjen I, Shumnalieva R, Vural S, Kötter I, van de Sande MG, Boyvat A, de Boer JH, Bertsias G, de Vries N, Krieckaert CL, Leal I, Vidovič Valentinčič N, Tugal-Tutkun I, El Khaldi Ahanach H, Costantino F, Glatigny S, Mrazovac Zimak D, Lötscher F, Kerstens FG, Bakula M, Viera Sousa E, Böhm P, Bosman K, Kenna TJ, Powis SJ, Breban M, Gul A, Bowes J, Lories RJ, Nowatzky J, Wolbink GJ, McGonagle DG, and Turkstra F
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- Humans, Genetic Predisposition to Disease, Histocompatibility Antigens Class I genetics, Aminopeptidases genetics, Minor Histocompatibility Antigens genetics, Uveitis, Behcet Syndrome genetics, Spondylarthritis
- Abstract
The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication., Competing Interests: Competing interests: JCP: Grants or contracts from any entity German Research Foundation grants PR 241/5-2Consulting fees Boehringer IngelheimPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events paid activities as a speaker for Almirall, Boehringer Ingelheim, Janssen-Cilag, Novartis and Pfizer PK Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid All unpaid: Human Immunology (Elsevier) Editorial Board, Frontiers in Immunology Guest associate, Editor and review editor. Editorial board of International Journal of Immunogenetics SS: all support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges, etc. Deutsche Forschungsgemeinschaft (DFG) to Jacobs University Bremen DM Grants or contracts from any entity Government of MaltaPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Sanofi, UriageSupport for attending meetings and/or travel Avene, Bioderma, UriageLeadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid Maltese Association of Dermatologists and VenereologistsIvan IP Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Novartis, Eli Lilly, Pfizer, Abbvie, Honoraria for lectures, payments directly to me RS Support for attending meetings and/or travel Abbvie and PfizerIna IK Consulting fees Amgen, Boehringer,GSK, SobiPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Abbvie, Amgen. Boehringer, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sobi MvdS Grants or contracts from any entity Novartis, UCB, EliLillyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events UCBSupport for attending meetings and/or travel UCBParticipation on a Data Safety Monitoring Board or Advisory Board Novartis, UCB, Abbvie GB Grants or contracts from any entity GSK, PfizerPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events GSK, AstraZeneca, Pfizer, Abbvie, Aenorasis, Novartis, Lilly IL Consulting fees Novartis, Alimera lT-T Consulting fees AbbVie, Turkey, NovartisPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events AbbVie, Turkey FC Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events LillySupport for attending meetings and/or travel UCB, NovartisParticipation on a data safety monitoring board or Advisory Board UCB, Novartis DMZ Grants or contracts from any entity European Society of OphthalmologyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Zentiva, Alkaloid d.o.o., Inspharma d.o.o. MB Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Pfizer, Viatris, Lilly, MSD TJK All support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges, etc). National Health & Medical Research Council GNT2011115Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid President, Australian Society for Medical Research MB Grants or contracts from any entity PFIZERConsulting fees PFIZERPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events FRENESIUS KABI, LILLYSupport for attending meetings and/or travel BIOGEN, PFIZER, JANSSEN RJUL Consulting fees UCB, Novartis, Abbvie, Eli-LillyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events UCB, Novartis, Abbvie, Eli-Lilly, Amgen JN All research funding support for the present manuscript: NEI-NIH R01EY033495—research funds and R01EY031383—research fundsHonoraria for lectures: Harvard University, Northwestern University, Massachusetts General Hospital.Support for attending meetings and/or travel: NYU Department of Medicine, NIH-NEIParticipation Medical Advisory Board: ABDA (American Behçet’s Disease Association) DGMcG Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Janssen, Abbvie, Novartis, UCB, BMS, Lilly., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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21. Spesolimab improves patient-reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study.
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Navarini AA, Prinz JC, Morita A, Tsai TF, Viguier MA, Li L, Thoma C, Sivalingam M, and Lebwohl MG
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- Humans, Treatment Outcome, Chronic Disease, Pain, Quality of Life, Psoriasis drug therapy
- Abstract
Background: Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease with a considerable clinical burden. In the Effisayil™ 1 study, spesolimab, an anti-interleukin-36 receptor monoclonal antibody, demonstrated efficacy in treating GPP flares., Objectives: To evaluate patient-reported outcomes (PROs) of patients with GPP who were treated with intravenous (IV) spesolimab 900 mg in the Effisayil™ 1 study., Methods: Fifty-three patients presenting with a GPP flare were randomized (2:1) to receive a single dose of IV spesolimab 900 mg or placebo and were followed for 12 weeks. Four PROs (pain visual analogue scale [pain VAS]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]; Dermatology Life Quality Index [DLQI]; and Psoriasis Symptom Scale [PSS]) were assessed throughout the 12-week study. Minimal clinically important differences (MCIDs) were defined. All data are reported descriptively., Results: In patients who received spesolimab, improvements from baseline (median [Q1, Q3]) were observed in pain VAS (-21.3 [-55.3, -3.1]), FACIT-Fatigue (7.0 [1.0, 20.0]), DLQI (-2.5 [-8.0, 1.0]) and PSS (-4.0 [-7.0, 0.0]) within 1 week of treatment. These improvements were sustained over 12 weeks and corresponded to the achievement of MCIDs at Week 1, which were also sustained over 12 weeks. Patients in the placebo arm experienced improvements in PROs and achievement of MCIDs after receipt of open-label spesolimab at Week 1., Conclusions: Patients with a GPP flare treated with spesolimab achieved improvements in PROs by Week 1, which were sustained for 12 weeks, and achieved MCIDs as early as Week 1., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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22. Generalized pustular psoriasis: A global Delphi consensus on clinical course, diagnosis, treatment goals and disease management.
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Puig L, Choon SE, Gottlieb AB, Marrakchi S, Prinz JC, Romiti R, Tada Y, von Bredow D, and Gooderham M
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- Humans, Consensus, Delphi Technique, Disease Management, Disease Progression, Goals, Psoriasis therapy, Psoriasis drug therapy
- Abstract
Background: Generalized pustular psoriasis (GPP) is a rare and highly heterogeneous skin disease, characterized by flares of neutrophilic pustules and erythema. As a rare disease with few clinical studies and no standardized management approaches, there is a paucity of knowledge regarding GPP., Objectives: Conduct a Delphi panel study to identify current evidence and gain advanced insights into GPP., Methods: A systematic literature review was used to identify published literature and develop statements categorized into four key domains: clinical course and flare definition; diagnosis; treatment goals; and holistic management. Statements were rated on a Likert scale by a panel of dermatologists in two rounds of online questionnaires; the threshold for consensus was agreement by ≥80%., Results: Twenty-one panellists reached consensus on 70.9%, 61.8%, 100.0% and 81.8% of statements in the 'clinical course and flare definition', 'diagnosis', 'treatment goals' and 'holistic management of GPP' domains, respectively. There was clear consensus on GPP being phenotypically, genetically and immunologically distinct from plaque psoriasis. Clinical course is highly variable, with an extensive range of complications. Clinical and histologic features supporting GPP diagnosis reached high levels of agreement, and although laboratory evaluations were considered helpful for diagnosis and monitoring disease severity, there was uncertainty around the value of individual tests. All acute and long-term treatment goals reached consensus, including rapid and sustained clearance of pustules, erythema, scaling and crust, clearance of skin lesions and prevention of new flares. Potential triggers, associated comorbidities and differential diagnoses achieved low rates of consensus, indicating that further evidence is needed., Conclusions: Global consensus between dermatologists was reached on clinically meaningful goals for GPP treatment, on key features of GPP flares and on approaches for assessing disease severity and multidisciplinary management of patients. On this basis, we present a management algorithm for patients with GPP for use in clinical practice., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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23. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review.
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Prinz JC, Choon SE, Griffiths CEM, Merola JF, Morita A, Ashcroft DM, and Viguier M
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- Humans, Prevalence, Mutation, Psoriasis epidemiology, Psoriasis genetics, Skin Diseases, Vesiculobullous, Dermatitis
- Abstract
Generalized pustular psoriasis (GPP) is a rare auto-inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life-threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non-standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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24. Immunogenic self-peptides - the great unknowns in autoimmunity: Identifying T-cell epitopes driving the autoimmune response in autoimmune diseases.
- Author
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Prinz JC
- Subjects
- Humans, Epitopes, T-Lymphocyte, CD8-Positive T-Lymphocytes, Peptides, Receptors, Antigen, T-Cell metabolism, Autoimmunity, Autoimmune Diseases
- Abstract
HLA-associated autoimmune diseases likely arise from T-cell-mediated autoimmune responses against certain self-peptides from the broad HLA-presented immunopeptidomes. The limited knowledge of the autoimmune target peptides has so far compromised the basic understanding of autoimmune pathogenesis. This is due to the complexity of antigen processing and presentation as well as the polyspecificity of T-cell receptors (TCRs), which pose high methodological challenges on the discovery of immunogenic self-peptides. HLA-class I molecules present peptides to CD8
+ T cells primarily derived from cytoplasmic proteins. Therefore, HLA-class I-restricted autoimmune responses should be directed against target cells expressing the corresponding parental protein. In HLA-class II-associated diseases, the origin of immunogenic peptides is not pre-specified, because peptides presented by HLA-class II molecules to CD4+ T cells may originate from both extracellular and cellular self-proteins. The different origins of HLA-class I and class II presented peptides determine the respective strategy for the discovery of immunogenic self-peptides in approaches based on the TCRs isolated from clonally expanded pathogenic T cells. Both involve identifying the respective restricting HLA allele as well as determining the recognition motif of the TCR under investigation by peptide library screening, which is required to search for homologous immunogenic self-peptides. In HLA-class I-associated autoimmune diseases, identification of the target cells allows for defining the restricting HLA allotype from the 6 different HLA-class I alleles of the individual HLA haplotype. It furthermore limits the search for immunogenic self-peptides to the transcriptome or immunopeptidome of the target cells, although neoepitopes generated by peptide splicing or translational errors may complicate identification. In HLA class II-associated autoimmune diseases, the lack of a defined target cell and differential antigen processing in different antigen-presenting cells complicate identification of the HLA restriction of autoreactive TCRs from CD4+ T cells. To avoid that all corresponding HLA-class II allotypes have to be included in the peptide discovery, autoantigens defined by autoantibodies can guide the search for immunogenic self-peptides presented by the respective HLA-class II risk allele. The objective of this article is to highlight important aspects to be considered in the discovery of immunogenic self-peptides in autoimmune diseases., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Prinz.)- Published
- 2023
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25. Influence of Covid-19 vaccination on immune-mediated skin diseases.
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Alelq NA, Kubieniec ME, French LE, and Prinz JC
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- Humans, COVID-19 Vaccines, Vaccination, COVID-19 prevention & control, Skin Diseases
- Published
- 2022
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26. International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.
- Author
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van Huizen AM, Menting SP, Gyulai R, Iversen L, van der Kraaij GE, Middelkamp-Hup MA, Warren RB, Spuls PI, Schejtman AA, Egeberg A, Firooz A, Kumar AS, Oakley A, Foulkes A, Ramos AMC, Fougerousse AC, Carija A, Akman-Karakas A, Horváth B, Fábos B, Matlock BH, Claréus BW, Castro C, Ferrándiz C, Correa CC, Marchesi C, Goujon C, Gonzalez C, Maldonado-García C, Hong CH, Griffiths CEM, Vestergaard C, Echeverría CM, de la Cruz C, Conrad C, Törocsik D, Drvar DL, Balak D, Jullien D, Appelen D, Kim DH, de Jong EMGJ, El Gamal E, Laffitte E, Mahé E, Sonkoly E, Colombo EP, Vilarrasa E, Willaert F, Novoa FD, Handjani F, Valenzuela F, Vílchez-Márquez F, Gonzalez GO, Krisztián G, Damiani G, Krnjevic-Pezic G, Pellerano G, Carretero G, Hunter HJA, Riad H, Oon HH, Boonen HPJ, Moussa IO, García-Doval I, Csányi I, Brajac I, Turchin I, Grozdev I, Weinberg JM, Nicolopoulos J, Wells J, Lambert JLW, Ingram JR, Prinz JC, de Souza Sittart JA, Sanchez JL, Hsiao JP, Castro-Ayarza JR, Maul JT, van den Reek JMPA, Trcko K, Barber K, Reich K, Gebauer KA, Khobzei K, Maul LV, Massari LP, Fardet L, le Cleach L, Misery L, Chandrashekar L, Muresanu LI, Lecluse L, Skov L, Frez ML, Babic LT, Puig L, Gomez LC, Ramam M, Dutil M, El-Sayed MH, Olszewska M, Schram ME, Franco MD, Llamas-Velasco M, Gonçalo M, Velásquez-Lopera MM, Abad ME, de Oliveira MFSP, Seyger MMB, Kaštelan M, Rademaker M, Sikora M, Lebwohl M, Wiseman MC, Ferran M, van Doorn M, Danespazhooh M, Bylaite-Bucinskiene M, Gooderham MJ, Polic MV, de Rie MA, Zheng M, Gómez-Flores M, Salleras I Redonnet M, Silverberg NB, Doss N, Yawalkar N, Chosidow O, Zargari O, de la Cueva P, Fernandez-Peñas P, Cárdenas Rojas PJ, Gisondi P, Grewal P, Sator P, Luna PC, Félix PAO, Varela P, Holló P, Cetkovska P, Calzavara-Pinton P, Ghislain PD, Araujo RR, Romiti R, Kui R, Ceovic R, Vender R, Lafuente-Urrez RF, Del-Río R, Gulin SJ, Handa S, Mahil SK, Kolalapudi SA, Marrón SE, Azimi SZ, Janmohamed SR, da Cruz Costa SA, Choon SE, Urbancek S, Ayanlowo O, Margasin SM, Wong TW, Mälkönen T, Hurtová T, Reciné TR, Huldt-Nystrøm T, Torres T, Liu TY, Leonidze T, Sharma VK, Weightman W, Gulliver W, and Veldkamp W
- Subjects
- Adult, Child, Consensus, Folic Acid, Humans, Surveys and Questionnaires, Methotrexate, Psoriasis therapy
- Abstract
Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide., Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics., Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience)., Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree., Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients., Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
- Published
- 2022
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27. ["Joy and friendship through research" : On the occasion of the 100th birthday of Prof. Dr. med. Dr. h.c. mult. Otto Braun-Falco].
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Prinz JC and French LE
- Published
- 2022
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28. Antigen Processing, Presentation, and Tolerance: Role in Autoimmune Skin Diseases.
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Prinz JC
- Subjects
- Antigen Presentation genetics, Autoantigens, Humans, Immune Tolerance, Receptors, Antigen, T-Cell metabolism, Autoimmune Diseases genetics, Skin Diseases genetics
- Abstract
Autoreactive T cells pose a constant risk for the emergence of autoimmune skin diseases in genetically predisposed individuals carrying certain HLA risk alleles. Immune tolerance mechanisms are opposed by broad HLA-presented self-immunopeptidomes, a predefined repertoire of polyspecific TCRs, the continuous generation of new antibody specificities by somatic recombination of Ig genes in B cells, and heightened proinflammatory reactivity. Increased autoantigen presentation by HLA molecules, cross-activation of pathogen-induced T cells against autologous structures, altered metabolism of self-proteins, and excessive production of proinflammatory signals may all contribute to the breakdown of immune tolerance and the development of autoimmune skin diseases., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
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29. Biologics and small molecules in patients with scalp psoriasis: a systematic review.
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Alsenaid A, Ezmerli M, Srour J, Heppt M, Illigens BM, and Prinz JC
- Subjects
- Humans, Quality of Life, Scalp, Severity of Illness Index, Treatment Outcome, Biological Products therapeutic use, Psoriasis drug therapy
- Abstract
Background: Scalp psoriasis is common in psoriasis patients, difficult to treat and manifests a significant burden on quality of life., Objective: Efficacy assessment of biologics and small molecules in scalp psoriasis with reported safety and quality of life., Methods: Biological therapies and small molecules licensed for treatment of plaque psoriasis are assessed. Fourteen studies reporting results from RCTs are included. Efficacy assessment is measured through improvement of Psoriasis Scalp Severity Index (PSSI), Scalp Physician Global Assessment (ScPGA) and/or Scalp-Specific Investigator's Global Assessment (ss-IGA)., Results: Among biologics measured by PSSI, brodalumab, secukinumab and in a subgroup ixekizumab showed high efficacy in moderate to severe scalp psoriasis. Both brodalumab and ixekizumab demonstrated rapid response within 2 weeks. Guselkumab was superior to adalimumab and ixekizumab was superior to etanercept. Apremilast showed long-term efficacy. Only few studies reported quality of life in treatment of scalp involvement which showed improvement. All treatments demonstrated acceptable safety profile., Conclusion: Effective treatment of scalp psoriasis is essential for improving the quality of life of psoriasis patients. Both Biologics and small molecules proved efficacy. This review may help choosing the appropriate treatment in cases where scalp psoriasis is the main complaint. A unified measurement tool for scalp psoriasis severity is needed to facilitate comparisons.
- Published
- 2022
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30. Lesional activation of T c 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.
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Vural S, Kerl K, Ertop Doğan P, Vollmer S, Puchta U, He M, Arakawa Y, Heper AO, Karal-Öktem A, Hartmann D, Boyvat A, Prinz JC, and Arakawa A
- Subjects
- Aminopeptidases metabolism, Autoimmunity, CD8-Positive T-Lymphocytes, Humans, Minor Histocompatibility Antigens metabolism, Behcet Syndrome pathology, Extracellular Traps, Psoriasis
- Abstract
Background: Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils., Objectives: To determine pathological changes in BD skin lesions related to the complex genetic predisposition., Methods: We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation., Results: We found that in BD lesions, as in psoriasis, actively expanding CD8
+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs)., Conclusions: In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)- Published
- 2021
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31. ERAP1 Controls the Autoimmune Response against Melanocytes in Psoriasis by Generating the Melanocyte Autoantigen and Regulating Its Amount for HLA-C*06:02 Presentation.
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Arakawa A, Reeves E, Vollmer S, Arakawa Y, He M, Galinski A, Stöhr J, Dornmair K, James E, and Prinz JC
- Subjects
- Aminopeptidases genetics, Antigen Presentation, Autoantigens immunology, Autoimmunity, Gene Knockdown Techniques, Genetic Predisposition to Disease, HEK293 Cells, HLA-C Antigens genetics, Humans, Minor Histocompatibility Antigens genetics, Molecular Targeted Therapy, Psoriasis genetics, Receptors, Antigen, T-Cell metabolism, Risk, Aminopeptidases metabolism, CD8-Positive T-Lymphocytes immunology, HLA-C Antigens metabolism, Melanocytes immunology, Minor Histocompatibility Antigens metabolism, Psoriasis immunology
- Abstract
Autoimmune diseases develop when autoantigens activate previously quiescent self-reactive lymphocytes. Gene-gene interaction between certain HLA class I risk alleles and variants of the endoplasmic reticulum aminopeptidase ERAP1 controls the risk for common immune-mediated diseases, including psoriasis, ankylosing spondylitis, and Behçet disease. The functional mechanisms underlying this statistical association are unknown. In psoriasis, HLA-C*06:02 mediates an autoimmune response against melanocytes by autoantigen presentation. Using various genetically modified cell lines together with an autoreactive psoriatic TCR in a TCR activation assay, we demonstrate in this study that in psoriasis, ERAP1 generates the causative melanocyte autoantigen through trimming N-terminal elongated peptide precursors to the appropriate length for presentation by HLA-C*06:02. An ERAP1 risk haplotype for psoriasis produced the autoantigen much more efficiently and increased HLA-C expression and stimulation of the psoriatic TCR by melanocytes significantly more than a protective haplotype. Compared with the overall HLA class I molecules, cell surface expression of HLA-C decreased significantly more upon ERAP1 knockout. The combined upregulation of ERAP1 and HLA-C on melanocytes in psoriasis lesions emphasizes the pathogenic relevance of their interaction in patients. We conclude that in psoriasis pathogenesis, the increased generation of an ERAP1-dependent autoantigen by an ERAP1 risk haplotype enhances the likelihood that autoantigen presentation by HLA-C*06:02 will exceed the threshold for activation of potentially autoreactive T cells, thereby triggering CD8
+ T cell-mediated autoimmune disease. These data identify ERAP1 function as a central checkpoint and promising therapeutic target in psoriasis and possibly other HLA class I-associated diseases with a similar genetic predisposition., (Copyright © 2021 by The American Association of Immunologists, Inc.)- Published
- 2021
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32. Genetic Analysis of MPO Variants in Four Psoriasis Subtypes in Patients from Germany.
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Haskamp S, Horowitz JS, Oji V, Philipp S, Sticherling M, Schäkel K, Schuhmann S, Prinz JC, Burkhardt H, Behrens F, Böhm B, Köhm M, Rech J, Simon D, Schett G, Morrison K, Gerdes S, Assmann G, Nimeh A, Schuster V, Jacobi A, Weyergraf A, Reis A, Uebe S, Wilsmann-Theis D, Mößner R, and Hüffmeier U
- Subjects
- Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic epidemiology, Genetic Testing, Germany epidemiology, Humans, Polymorphism, Single Nucleotide, Psoriasis diagnosis, Psoriasis epidemiology, Severity of Illness Index, Arthritis, Psoriatic genetics, Genetic Predisposition to Disease, Peroxidase genetics, Psoriasis genetics
- Published
- 2021
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33. [Dermatology continuing medical education during Corona times and beyond : Experience from the 2020 digital advanced training week for practical dermatology and venerology and lessons for future concepts].
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Prinz JC, Hartmann D, Wolff H, Schlaak MS, Pilz J, Ruzicka T, Preußner M, Kiendl C, Greger J, Mutke S, and French LE
- Subjects
- Diagnostic Tests, Routine, Humans, Dermatology education, Education, Medical, Continuing
- Published
- 2021
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34. Myeloperoxidase Modulates Inflammation in Generalized Pustular Psoriasis and Additional Rare Pustular Skin Diseases.
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Haskamp S, Bruns H, Hahn M, Hoffmann M, Gregor A, Löhr S, Hahn J, Schauer C, Ringer M, Flamann C, Frey B, Lesner A, Thiel CT, Ekici AB, von Hörsten S, Aßmann G, Riepe C, Euler M, Schäkel K, Philipp S, Prinz JC, Mößner R, Kersting F, Sticherling M, Sefiani A, Lyahyai J, Sondermann W, Oji V, Schulz P, Wilsmann-Theis D, Sticht H, Schett G, Reis A, Uebe S, Frey S, and Hüffmeier U
- Subjects
- Adult, Animals, Cytokines genetics, Extracellular Traps genetics, Female, Humans, Inflammation pathology, Interleukin-1 genetics, Interleukins metabolism, Male, Mice, Mutation genetics, Neutrophils metabolism, Psoriasis pathology, Rare Diseases enzymology, Rare Diseases genetics, Rare Diseases pathology, Skin enzymology, Skin pathology, Skin Diseases pathology, Inflammation genetics, Interleukins genetics, Peroxidase genetics, Psoriasis genetics, Skin Diseases genetics
- Abstract
Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%-41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E-08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E-09); this effect was stronger when including IL36RN mutations (1.48E-13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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35. Rare Loss-of-Function Mutation in SERPINA3 in Generalized Pustular Psoriasis.
- Author
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Frey S, Sticht H, Wilsmann-Theis D, Gerschütz A, Wolf K, Löhr S, Haskamp S, Frey B, Hahn M, Ekici AB, Uebe S, Thiel C, Reis A, Burkhardt H, Behrens F, Köhm M, Rech J, Schett G, Assmann G, Kingo K, Kõks S, Mössner R, Prinz JC, Oji V, Schulz P, Muñoz LE, Kremer AE, Wenzel J, and Hüffmeier U
- Subjects
- Adult, Aged, Alleles, Exanthema, Female, Genetic Predisposition to Disease, HaCaT Cells, Heterozygote, Humans, Male, Middle Aged, Mutation, Mutation, Missense, Psoriasis genetics, Serpins genetics, Skin Diseases, Vesiculobullous genetics
- Published
- 2020
- Full Text
- View/download PDF
36. [Psoriasis in dupilumab-treated atopic dermatitis].
- Author
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Senner S, Eicher L, Aszodi N, Prinz JC, French LE, and Wollenberg A
- Subjects
- Adult, Humans, Male, Treatment Outcome, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized therapeutic use, Dermatitis, Atopic drug therapy, Psoriasis chemically induced
- Abstract
Dupilumab is a monoclonal antibody that binds to the common alpha chain of the IL‑4 and IL-13 receptor and blocks the Th2 signaling pathway, which plays a key role in the development of atopic dermatitis. We report on the case of a 40-year-old man, who developed histologically confirmed psoriasis after 6 weeks of dupilumab therapy. The arbitrary, abrupt stopping of the unusual, not guideline-based oral steroid therapy, together with the blockade of the Th2 signaling pathway by dupilumab were apparently the relevant trigger factors for the newly developed psoriasis in our patient.
- Published
- 2020
- Full Text
- View/download PDF
37. The Woronoff Ring in Psoriasis and the Mechanisms of Postinflammatory Hypopigmentation.
- Author
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Prinz JC
- Subjects
- Aged, CD8-Positive T-Lymphocytes metabolism, Cell Proliferation, Female, Humans, Hypopigmentation pathology, Interleukin-17 metabolism, Psoriasis pathology, Tumor Necrosis Factor-alpha metabolism, CD8-Positive T-Lymphocytes immunology, Hypopigmentation etiology, Melanins biosynthesis, Melanocytes physiology, Psoriasis complications, Psoriasis immunology
- Abstract
The Woronoff ring is a ring-like hypopigmentation zone around regressing psoriasis lesions. Although it was first described more than 100 years ago, its aetiology has remained a mystery. Recent insights into the pathogenesis of psoriasis can now explain the origin of the Woronoff ring. Psoriasis involves an HLA-class I-restricted autoimmune response of CD8+ T cells against melanocytes in the epidermis. The pathogenic CD8+ T cells are not cytotoxic, but are characterized by the production of interleukin-17, interleukin-22 and tumour necrosis factor-α. Interleukin-17 and tumour necrosis factor-α act synergistically on melanocytes by increasing proliferation while inhibiting melanogenesis. This reduces the cellular melanin content despite an increased number of melanocytes in psoriatic lesions. As a consequence, during healing the prior influence of interleukin-17 and tumour necrosis factor-α, despite the increased density of melanocytes, leaves a hypopigmented zone at the edge of regressing psoriasis lesions, which becomes visible as the Woronoff ring. This mechanism can explain a long-discussed puzzling phenomenon in dermatology.
- Published
- 2020
- Full Text
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38. Clonality of CD4 + Blood T Cells Predicts Longer Survival With CTLA4 or PD-1 Checkpoint Inhibition in Advanced Melanoma.
- Author
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Arakawa A, Vollmer S, Tietze J, Galinski A, Heppt MV, Bürdek M, Berking C, and Prinz JC
- Subjects
- Adult, Aged, CD8-Positive T-Lymphocytes immunology, Female, Humans, Immunotherapy methods, Lymphocytes, Tumor-Infiltrating immunology, Male, Middle Aged, Tumor Microenvironment immunology, CD4-Positive T-Lymphocytes immunology, CTLA-4 Antigen immunology, Melanoma immunology, Programmed Cell Death 1 Receptor immunology
- Abstract
Recognition of cancer antigens drives the clonal expansion of cancer-reactive T cells, which is thought to contribute to restricted T-cell receptor (TCR) repertoires in tumor-infiltrating lymphocytes (TILs). To understand how tumors escape anti-tumor immunity, we investigated tumor-associated T-cell repertoires of patients with advanced melanoma and after blockade of the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PD-1). TCR Vβ-gene spectratyping allowed us to quantify restrictions of T-cell repertoires and, further, diversities of T-cell clones. In this study, we show that the blood TCR repertoires were variably restricted in CD4
+ and extensively restricted in CD8+ T cells of patients with advanced melanoma, and contained clones in both T-cell fractions prior to the start of immunotherapy. A greater diversification especially of CD4+ blood T-cell clones before immunotherapy showed statistically significant correlations with long-term survival upon CTLA4 or PD-1 inhibition. Analysis of TILs and corresponding blood available in one patient indicated that blood clonality may at least partially be related to the clonal expansion in the tumor microenvironment. In patients who developed severe immune-related adverse events (IrAEs), CD4+ and CD8+ TCR spectratypes became more restricted during anti-CTLA4 treatment, suggesting that newly expanded oligoclonal T-cell responses may contribute to IrAEs. This study reveals diverse T-cell clones in the blood of melanoma patients prior to immunotherapy, which may reflect the extent to which T cells are able to react against melanoma and potentially control melanoma progression. Therefore, the T-cell clonality in the circulation may have predictive value for antitumor responses from checkpoint inhibition.- Published
- 2019
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39. Laudatio zum 80. Geburtstag für Prof. Dr. med. Dr. h.c. mult. Gerd Plewig.
- Author
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French L, Prinz JC, and Bruckner-Tuderman L
- Published
- 2019
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40. [In honor of Prof. Dr. med. Dr. h.c. mult. Gerd Plewig on the occasion of his 80th birthday : Gerd Plewid-a lifetime for dermatology].
- Author
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Bruckner-Tuderman L, French L, and Prinz JC
- Subjects
- Germany, History, 20th Century, Dermatology history
- Published
- 2019
- Full Text
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41. Intracellular Streptococcal Uptake and Persistence: A Potential Cause of Erysipelas Recurrence.
- Author
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Jendoubi F, Rohde M, and Prinz JC
- Abstract
Erysipelas is a severe streptococcal infection of the skin primarily spreading through the lymphatic vessels. Penicillin is the treatment of choice. The most common complication consists in relapses which occur in up to 40% or more of patients despite appropriate antibiotic treatment. They cause lymphatic damage resulting in irreversible lymphedema and ultimately elephantiasis nostras and lead to major health restrictions and high socio-medical costs. Prevention of relapses is an unmet need, because even long-term prophylactic penicillin application does eventually not reduce the risk of recurrence. In this article we assess risk factors and causes of erysipelas recurrence. A systematic literature search for clinical studies addressing potential causes and measures for prevention of erysipelas recurrence was combined with a review of experimental and clinical data assessing the ability and clinical relevance of streptococci for intracellular uptake and persistence. The literature review found that venous insufficiency, lymphedema, and intertrigo from fungal infections are considered to be major risk factors for recurrence of erysipelas but cannot adequately explain the high recurrence rate. As hitherto unrecognized likely cause of erysipelas relapses we identify the ability of streptococci for intracellular uptake into and persistence within epithelial and endothelial cells and macrophages. This creates intracellular streptococcal reservoirs out of reach of penicillins which do not reach sufficient bactericidal intracellular concentrations. Incomplete streptococcal elimination due to intracellular streptococcal persistence has been observed in various deep tissue infections and is considered as cause of relapsing streptococcal pharyngitis despite proper antibiotic treatment. It may also serves as endogenous infectious source of erysipelas relapses. We conclude that the current antibiotic treatment strategies and elimination of conventional risk factors employed in erysipelas management are insufficient to prevent erysipelas recurrence. The reactivation of streptococcal infection from intracellular reservoirs represents a plausible explanation for the frequent occurrence erysipelas relapses. Prevention of erysipelas relapses therefore demands for novel antibiotic strategies capable of eradicating intracellular streptococcal persistence.
- Published
- 2019
- Full Text
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42. Renal clearance and intracellular half-life essentially determine methotrexate toxicity: A case series.
- Author
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Arakawa Y, Arakawa A, Vural S, Mahajan R, and Prinz JC
- Published
- 2018
- Full Text
- View/download PDF
43. The therapeutic potential of TNF-α antagonists in toxic epidermal necrosis: insights from two cases and adverse event reports.
- Author
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Vural S, Arakawa A, Arakawa Y, and Prinz JC
- Subjects
- Anti-Bacterial Agents adverse effects, Ciprofloxacin adverse effects, Dermatologic Agents therapeutic use, Female, Humans, Middle Aged, Psoriasis drug therapy, Stevens-Johnson Syndrome etiology, Stevens-Johnson Syndrome prevention & control, Adalimumab therapeutic use, Etanercept therapeutic use, Stevens-Johnson Syndrome drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Published
- 2018
- Full Text
- View/download PDF
44. Unopposed IL-36 Activity Promotes Clonal CD4 + T-Cell Responses with IL-17A Production in Generalized Pustular Psoriasis.
- Author
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Arakawa A, Vollmer S, Besgen P, Galinski A, Summer B, Kawakami Y, Wollenberg A, Dornmair K, Spannagl M, Ruzicka T, Thomas P, and Prinz JC
- Subjects
- Adult, Aged, Autoantigens immunology, Female, Histocompatibility Antigens Class II immunology, Histocompatibility Antigens Class II metabolism, Humans, Interleukin-1 immunology, Interleukin-17 immunology, Interleukins genetics, Interleukins immunology, Male, Middle Aged, Psoriasis genetics, Psoriasis pathology, Receptors, Antigen, T-Cell immunology, Receptors, Antigen, T-Cell metabolism, Skin immunology, Skin metabolism, Skin pathology, Th17 Cells metabolism, Young Adult, Autoimmunity, Interleukin-1 metabolism, Interleukin-17 metabolism, Psoriasis immunology, Th17 Cells immunology
- Abstract
Generalized pustular psoriasis (GPP) is the most severe psoriasis variant. Mutations in the IL-36 antagonist IL36RN, in CARD14 or AP1S3 provide genetic evidence for autoinflammatory etiology but cannot explain its pathogenesis completely. Here we demonstrate that unopposed IL-36 signaling promotes antigen-driven and likely pathogenic T-helper type 17 (Th17) responses in GPP. We observed that CD4
+ T cells in blood and skin lesions of GPP patients were characterized by intense hyperproliferation, production of the GPP key mediator, IL-17A, and highly restricted TCR repertoires with identical T-cell clones in blood and skin lesions, indicating antigen-driven T-cell expansions. The clonally expanded CD4+ T cells were major producers of IL-17A. IL-36 signaling substantially enhanced TCR-mediated proliferation of CD4+ T cells. Moreover, GPP patients showed preferences for HLA-DRB1∗14, HLA-DQB1∗05, and HLA-DQB1∗03. We conclude that in GPP unopposed IL-36 signaling and certain HLA-class II alleles may cooperate in promoting antigen-driven Th17 responses, which in the obvious absence of exogenous triggers may reflect autoimmune reactions. This study reveals a pathogenic pathway where innate immune dysregulation promotes T-cell-mediated inflammation in GPP., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
45. Simultaneous Response in Several Domains in Patients with Psoriatic Disease Treated with Etanercept as Monotherapy or in Combination with Conventional Synthetic Disease-modifying Antirheumatic Drugs.
- Author
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Behrens F, Meier L, Prinz JC, Jobst J, Lippe R, Löschmann PA, and Lorenz HM
- Subjects
- Adult, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prospective Studies, Quality of Life, Treatment Outcome, Antirheumatic Agents therapeutic use, Arthritis, Psoriatic drug therapy, Etanercept therapeutic use, Methotrexate therapeutic use, Psoriasis drug therapy
- Abstract
Objective: To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously., Methods: A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary., Results: Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group., Conclusion: While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.
- Published
- 2018
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46. Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis.
- Author
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Prinz JC
- Subjects
- Alleles, Autoantigens immunology, Epidermis immunology, Genetic Predisposition to Disease, Humans, Melanocytes immunology, Skin immunology, Skin pathology, Autoimmunity, CD8-Positive T-Lymphocytes immunology, Histocompatibility Antigens Class I genetics, Psoriasis genetics, Psoriasis pathology
- Abstract
Psoriasis is a complex immune-mediated inflammatory skin disease characterized by T-cell-driven epidermal hyperplasia. It occurs on a strong genetic predisposition. The human leukocyte antigen (HLA)-class I allele HLA-C*06:02 on psoriasis susceptibility locus 1 (PSORS1 on 6p21.3) is the main psoriasis risk gene. Other HLA-class I alleles encoding HLA molecules presenting overlapping peptide repertoires show associations with psoriasis as well. Outside the major histocompatibility complex region, genome-wide association studies identified more than 60 psoriasis-associated common gene variants exerting only modest individual effects. They mainly refer to innate immune activation and the interleukin-23/T
h/c 17 pathway. Given their strong risk association, explaining the role of the HLA-risk alleles is essential for elucidating psoriasis pathogenesis. Psoriasis lesions develop upon epidermal infiltration, activation, and expansion of CD8+ T cells. The unbiased analysis of a paradigmatic Vα3S1/Vβ13S1-T-cell receptor from a pathogenic epidermal CD8+ T-cell clone of an HLA-C*06:02+ psoriasis patient had revealed that HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation, and it identified a peptide form ADAMTS-like protein 5 as an HLA-C*06:02-presented melanocyte autoantigen. These data demonstrate that psoriasis is an autoimmune disease, where the predisposing HLA-class I alleles promote organ-specific inflammation through facilitating a T-cell response against a particular skin-specific cell population. This review discusses the role of HLA-class I alleles in the pathogenic psoriatic T-cell immune response. It concludes that as a principle of T-cell driven HLA-associated inflammatory diseases proinflammatory traits promote autoimmunity in the context of certain HLA molecules that present particular autoantigens.- Published
- 2018
- Full Text
- View/download PDF
47. The genetic basis for most patients with pustular skin disease remains elusive.
- Author
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Mössner R, Wilsmann-Theis D, Oji V, Gkogkolou P, Löhr S, Schulz P, Körber A, Prinz JC, Renner R, Schäkel K, Vogelsang L, Peters KP, Philipp S, Reich K, Ständer H, Jacobi A, Weyergraf A, Kingo K, Kõks S, Gerdes S, Steinz K, Schill T, Griewank KG, Müller M, Frey S, Ebertsch L, Uebe S, Sticherling M, Sticht H, and Hüffmeier U
- Subjects
- Adult, CARD Signaling Adaptor Proteins genetics, Female, Genetic Predisposition to Disease genetics, Genetic Testing, Guanylate Cyclase genetics, Heterozygote, Humans, Male, Membrane Proteins genetics, Middle Aged, Vesicular Transport Proteins genetics, Interleukins genetics, Mutation genetics, Psoriasis genetics
- Abstract
Background: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP)., Objectives: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN., Methods: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort., Results: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers., Conclusions: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)
- Published
- 2018
- Full Text
- View/download PDF
48. Melanocytes: Target Cells of an HLA-C*06:02-Restricted Autoimmune Response in Psoriasis.
- Author
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Prinz JC
- Subjects
- HLA-C Antigens immunology, Humans, Melanocytes pathology, Psoriasis pathology, T-Lymphocytes immunology, Autoantigens immunology, Autoimmunity, Melanocytes immunology, Psoriasis immunology
- Abstract
HLA-C*06:02 is the main psoriasis risk allele. By the unbiased analysis of a Vα3S1/Vβ13S1 T-cell receptor from pathogenic psoriatic CD8
+ T cells, we had recently proven that HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation in psoriasis and identified ADAMTSL5 as a melanocyte autoantigen. We concluded that psoriasis is based on a melanocyte-specific immune response and that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. Understanding this pathway, however, requires more detailed explanation. It is based on the fact that an HLA class I-restricted autoreactive CD8+ T-cell response must be directed against a particular target cell type, because HLA class I molecules present peptide antigens generated from cytoplasmic (i.e., intracellular) proteins. This review summarizes the findings on the melanocyte-specific autoimmune response in the context of the immune mechanisms related to HLA function and T-cell receptor-antigen recognition. Identifying melanocytes as target cells of the psoriatic immune response now explains psoriasis as a primary autoimmune skin disease., (Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
49. The role of IL-23 and the IL-23/T H 17 immune axis in the pathogenesis and treatment of psoriasis.
- Author
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Girolomoni G, Strohal R, Puig L, Bachelez H, Barker J, Boehncke WH, and Prinz JC
- Subjects
- Dermatologic Agents therapeutic use, Humans, Immunity, Innate, Psoriasis epidemiology, United Kingdom epidemiology, Interleukin-23 physiology, Psoriasis drug therapy, Psoriasis immunology, Th17 Cells immunology
- Abstract
Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (T
H 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL-23, a heterodimer composed of a p40 subunit also found in IL-12 and a p19 subunit exclusive to IL-23. IL-23 is important for maintaining TH 17 responses, and levels of IL-23 are elevated in psoriatic skin compared with non-lesional skin. A number of agents that specifically inhibit IL-23p19 are currently in development for the treatment of moderate-to-severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL-23/TH 17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)- Published
- 2017
- Full Text
- View/download PDF
50. Autoimmune aspects of psoriasis: Heritability and autoantigens.
- Author
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Prinz JC
- Subjects
- Animals, Antigen Presentation, Autoantigens genetics, Autoantigens immunology, Autoimmunity, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, HLA Antigens genetics, Humans, Psoriasis immunology, Receptors, Antigen, T-Cell physiology, Psoriasis genetics
- Abstract
Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs. It concludes that disease-associated HLA alleles account for both missing heritability and autoimmune mechanisms by facilitating tissue-specific autoimmune responses through autoantigen presentation., (Copyright © 2017 The Author. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
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