26rhk264 10.3205/26rhk264 urn:nbn:de:0183-26rhk2645 Meeting Abstract Siedentopf Siedentopf Jorinde J

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Schmidt Schmidt Caroline C

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Hecker Hecker Friederike F

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Gruz Gruz Natalya N

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Krasselt Krasselt Marco M

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Pierer Pierer Matthias M

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author Wagner Wagner Ulf U

Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Experimentelle Rheumatologie, Leipzig, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20260909 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). M0656 264 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie Gesellschaft für Kinder- und Jugendrheumatologie 54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2026 Vaskulitiden & Kollagenosen Leipzig 20260909 20260912 VK.59 TextIntroduction: Systemic sclerosis (SSc) is a severe autoimmune disease characterized by progressive fibrosis of multiple organs and associated with high mortality . Up to 40% of patients develop painful calcinosis cutis, defined by calcium-phosphate deposition in the skin. The pathogenesis of this complication remains unclear and no established therapy exists . Calciprotein particles (CPPs) are nanoscale complexes composed of calcium, phosphate, and fetuin-A, and are already known to be taken up by monocytes, leading to increased production of pro-inflammatory cytokines , . CPPs may therefore represent a mechanistic link between mineral dysregulation, inflammation, fibrosis, and ectopic calcification. However, their role in systemic sclerosis remains unknown.Methods: To investigate this, circulating CPPs in the serum of SSc patients (n=33) and healthy controls (n=22) were directly stained with OsteoSense, a fluorophore-conjugated bisphosphonate, and quantified using imaging flow cytometry. Additionally, key parameters of calcium-phosphate metabolism and disease activity were analyzed. These include, among others, ionized calcium, phosphate, magnesium, parathyroid hormone, serum albumin, total protein, and renal function parameters.Results: Our results show that 30% of the SSc patients had increased CPP concentrations above the range of the healthy control group (>1.76 x 107 particles/ml, **p=0.0037, Fisher’s exact test), corresponding to an odds ratio of approximately 20. Notably, the highest levels of CPPs were observed in SSc patients with calcinosis cutis compared to the healthy control group (n=5 vs. n=22, mean=2.4 x 107 particles/ml vs. 1.19 x 107 particles/ml, **p=0.002). Moreover, SSc patients showed elevated levels of parathyroid hormone (mean=4.51 pmol/l vs. 3.56 pmol/l, *p=0.017) as well as decreased concentrations of ionized calcium (mean=1.233 mmol/l vs. 1.258 mmol/l, *p=0.03). The observed decrease in ionized calcium in SSc patients contradicts the physiological regulatory function of elevated parathyroid hormone levels and therefore suggests a dysregulation of mineral metabolism.Conclusion: In conclusion, our results suggest that CPPs may play a relevant role in the pathogenesis of calcinosis cutis and that their increased concentration might reflect a disturbed calcium buffering capacity of serum contributing to the disease. In addition, elevated CPP levels could stimulate monocytes to release pro-fibrotic and pro-calcific cytokines, thereby promoting fibrosis that provides a permissive environment for calcium-phosphate deposition.Disclosures: None declared. Volkmann ER Andréasson K Smith V Systemic sclerosis 2023 Lancet 304-318 Volkmann ER, Andréasson K, Smith V. Systemic sclerosis. Lancet. 2023 Jan 28;401(10373):304-318. DOI: 10.1016/S0140-6736(22)01692-0 http://dx.doi.org/10.1016/S0140-6736(22)01692-0 Davuluri S Lood C Chung L Calcinosis in systemic sclerosis 2024 Curr Opin Rheumatol 360-369 Davuluri S, Lood C, Chung L. Calcinosis in systemic sclerosis. Curr Opin Rheumatol. 2024 Sep 1;36(5):360-369. DOI: 10.1097/BOR.0000000000000900 http://dx.doi.org/10.1097/BOR.0000000000000900 Smith ER Holt SG The formation and function of calciprotein particles 2025 Pflugers Arch 753-772 Smith ER, Holt SG. The formation and function of calciprotein particles. Pflugers Arch. 2025 Jun;477(6):753-772. DOI: 10.1007/s00424-025-03083-7 http://dx.doi.org/10.1007/s00424-025-03083-7 Jäger E Murthy S Schmidt C Hahn M Strobel S Peters A Stäubert C Sungur P Venus T Geisler M Radusheva V Raps S Rothe K Scholz R Jung S Wagner S Pierer M Seifert O Chang W Estrela-Lopis I Raulien N Krohn K Sträter N Hoeppener S Schöneberg T Rossol M Wagner U Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis 2020 Nat Commun 4243 Jäger E, Murthy S, Schmidt C, Hahn M, Strobel S, Peters A, Stäubert C, Sungur P, Venus T, Geisler M, Radusheva V, Raps S, Rothe K, Scholz R, Jung S, Wagner S, Pierer M, Seifert O, Chang W, Estrela-Lopis I, Raulien N, Krohn K, Sträter N, Hoeppener S, Schöneberg T, Rossol M, Wagner U. Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis. Nat Commun. 2020 Aug 25;11(1):4243. DOI: 10.1038/s41467-020-17749-6 http://dx.doi.org/10.1038/s41467-020-17749-6 0 0 0 0