25rhk047 10.3205/25rhk047 urn:nbn:de:0183-25rhk0471 Meeting Abstract Tiessen Tiessen Esther E

Zentrum für Personalisierte Medizin (ZPMi) Ulm, Ulm Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author Maity Maity Pallab P

Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author Hall Hall Veronika V

Zentrum für Personalisierte Medizin (ZPMi) Ulm, Ulm Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author Maile Maile Lilly L

Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author Weiss Weiss Johannes M. JM

Zentrum für Personalisierte Medizin (ZPMi) Ulm, Ulm Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author Scharffetter-Kochanek Scharffetter-Kochanek Karin K

Universitätsklinik für Dermatologie & Allergologie Ulm, Ulm

author German Medical Science GMS Publishing House

Düsseldorf

610 20250917 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0627 047 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie 53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2025 Experimentelle & Translationale Rheumatologie Wiesbaden 20250917 20250920 ET.29 TextIntroduction: Generalized pustular psoriasis (GPP) is characterized by a dominant autoinflammatory component next to activation of the typical psoriatic IL-23/IL-17 cascade. GPP is an orphan disease with recurrent potentially life-threatening flares. According to psoriasis it is linked to several comorbidities like metabolic and cardiovascular diseases or depressive disorders. The objective of our study was to further decode immunological pathways in GPP as the maximal variant of pustular psoriasis in comparison to localized palmoplantar pustular psoriasis (PPP).Methods: Focusing on transcriptomic differences in GPP versus PPP, bulk RNA sequencing of affected and healthy skin of 3 GPP and 3 PPP patients was performed, and results between entities compared.Results: As a striking incidental finding a marked up-regulation of kynurenine (KYNU) and TDO2 (tryptophan 2,3-dioxygenase 2) was detected in GPP affected skin. Interestingly, in localized PPP KYNU and IDO1 (indoleamine 2,3-dioxygenase 1) were overexpressed in unaffected skin.Conclusion: The essential amino acid tryptophan is either metabolized in the KYNU pathway (catabolized by IDO and TDO) or serotonin pathway. The KYNU pathway is known to play a major role in T cell modulation. KYNU is e.g. involved in immune tolerance in gravidity and T cell apoptosis. Its metabolite quinolinic acid (QA) has direct pro-depressive neurotoxic effects and competes with glutamate which is crucial in the development of anxiety. Serotonin and its metabolite melatonin are important mood and sleep regulators. If KYNU is overexpressed due to the need of immunomodulation in acute disease or chronic inflammatory diseases (CID) a relative tryptophan lack towards serotonin pathway will result. Up-regulations of KYNU, IDO and TDO have already been found in periodontitis, hidradenitis suppurativa, inflammatory bowel diseases and COVID-19 infections. In the latter it led to a significant increase of suicidal behavior. Recently, markers of tryptophan catabolism were suggested as potential severity markers for diverse CID. Our findings close another gap between neuroimmunological animal models and clinical presentation of patients with CID. Sleeping disorders, depression and anxiety in CID seem to be caused to a significant degree by biochemical disturbances and require a consequent anti-inflammatory therapy. Agus A Planchais J Sokol H Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease 2018 Cell Host Microbe 716-24 Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018 Jun 13;23(6):716-24. DOI: 10.1016/j.chom.2018.05.003 http://dx.doi.org/10.1016/j.chom.2018.05.003 Bachelez H Barker J Burden AD Navarini AA Krueger JG Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion 2022 Expert Rev Clin Immunol 1033-47 Bachelez H, Barker J, Burden AD, Navarini AA, Krueger JG. Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion. Expert Rev Clin Immunol. 2022 Oct;18(10):1033-47. DOI: 10.1080/1744666X.2022.2116003 http://dx.doi.org/10.1080/1744666X.2022.2116003 Bertollo AG Mingoti MED Ignácio ZM Neurobiological mechanisms in the kynurenine pathway and major depressive disorder 2024 Rev Neurosci 169-87 Bertollo AG, Mingoti MED, Ignácio ZM. Neurobiological mechanisms in the kynurenine pathway and major depressive disorder. Rev Neurosci. 2024 Sep 9;36(2):169-87. DOI: 10.1515/revneuro-2024-0065 http://dx.doi.org/10.1515/revneuro-2024-0065 Harris DMM Szymczak S Schuchardt S Labrenz J Tran F Welz L Graßhoff H Zirpel H Sümbül M Oumari M Engelbogen N Junker R Conrad C Thaçi D Frey N Franke A Weidinger S Hoyer B Rosenstiel P Waschina S Schreiber S Aden K Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases 2024 EBioMedicine 105056 Harris DMM, Szymczak S, Schuchardt S, Labrenz J, Tran F, Welz L, Graßhoff H, Zirpel H, Sümbül M, Oumari M, Engelbogen N, Junker R, Conrad C, Thaçi D, Frey N, Franke A, Weidinger S, Hoyer B, Rosenstiel P, Waschina S, Schreiber S, Aden K. Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases. EBioMedicine. 2024 Apr;102:105056. 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