25rhk18110.3205/25rhk181urn:nbn:de:0183-25rhk1815Meeting AbstractSoluble checkpoint molecules as predictive biomarker for disease activity and long-term outcome in SLEDrevetonDrevetonLéa-SophieLSCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinauthorSpenckerSpenckerJakob JoachimJJMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinauthorRincon-ArevaloRincon-ArevaloHectorHCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinUniversidad de Antioquia UdeA, Grupo de Immunologia Cellular e Immunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, MedellinauthorAueAueArmanADeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinImmanuel-Krankenhaus Abteilung für Innere Medizin/Schwerpunkt Rheumatologie, BerlinauthorOsmanodjaOsmanodjaBilginBMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinauthorGlenzerGlenzerAnnikaACharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinauthorSzelinskiSzelinskiFranziskaFCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinauthorKrönkeKrönkeGerhardGCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinauthorDörnerDörnerThomasTCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinauthorSchrezenmeierSchrezenmeierEva V.EVDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinMedizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, BerlinauthorStefanskiStefanskiAna-LuisaALCharité – Campus Mitte Medizinische Klinik, Schwerpunkt Rheumatologie und Klinische Immunologie, BerlinDeutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, BerlinauthorGerman Medical Science GMS Publishing House
Düsseldorf
61020250917englThis 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).M0627181Deutsche Gesellschaft für RheumatologieDeutsche Gesellschaft für Orthopädische Rheumatologie53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)Deutscher Rheumatologiekongress 2025Vaskulitiden & KollagenosenWiesbaden2025091720250920VK.20TextIntroduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by systemic inflammation and multi-organ involvement. The heterogeneity of the disease poses a challenge for clinical assessment and treatment, indicating the need to develop personalized diagnostic and therapeutic approaches. Soluble immune checkpoint molecules (sICPs) have been identified as potential biomarkers for disease activity and treatment outcomes in autoimmune diseases , . However, their role in SLE remains unclear.Methods: Serum concentrations of various soluble co-stimulatory (sCD25, sCD27, sCD40L, s4-1BB, and sCD86) and co-inhibitory checkpoint molecules (sCTLA-4, sPD-1, sPD-L1, sPD-L2, sTim-3, sGal-9 and sLAG-3) were measured using a bead-based assay in 241 SLE patients who visited our departments between January 2016 and February 2023. sICPs were analyzed in relation to clinical data, including SLEDAI scores, organ-specific manifestations, long-term outcomes, and laboratory parameters (C3, C4, anti-dsDNA, and type I IFN signature/Siglec-1). Long-term remission was defined based on a comprehensive clinical assessment of disease activity and stability over time. The median disease duration was 8 years. Statistical analyses included Wilcoxon rank-sum tests, multivariate logistic regression, receiver operating characteristic (ROC) analyses, cluster analyses, and correlation matrices.Results: Higher sCD25, sTim-3, and sGal-9 concentrations were associated with active SLE (SLEDAI >4). Multivariate analyses, adjusted for age, sex, and prednisolone dose, confirmed these molecules as reliable disease activity predictors. (Figure 1 A, B ) Unsupervised Cluster analysis identified the highest concentrations of sCD25, sTim-3, and sGal-9 in an SLE subgroup with more severe disease activity (median SLEDAI 10).Strong positive correlations were observed between sCD25, sTim-3, and sGal-9 levels, suggesting that their upregulation may be driven by interrelated mechanisms. Interestingly, these molecules were specifically elevated in patients with renal involvement and/or anemia but not in those with APS, skin, or joint manifestations. Finally, low sCD25 levels were predictive of long-term and durable remission.Conclusion: This study identified sCD25, sTim-3, and sGal-9 as biomarkers for active SLE and specific organ involvement, particularly renal and hematologic. Low sCD25 levels were associated with durable remission, underscoring the potential as predictive and response biomarkers, and requiring further validation.Stefanski ALRincon-Arevalo HDressler-Steinbach INomovi NMackert AAue ARitter JWiedemann ASzelinski FSchrezenmeier EKühl AALino ACHenrich WDörner TDysregulation of immune checkpoint molecules as a characteristic of autoimmune congenital heart block2024Ann Rheum Dis1598-600Stefanski AL, Rincon-Arevalo H, Dressler-Steinbach I, Nomovi N, Mackert A, Aue A, Ritter J, Wiedemann A, Szelinski F, Schrezenmeier E, Kühl AA, Lino AC, Henrich W, Dörner T. Dysregulation of immune checkpoint molecules as a characteristic of autoimmune congenital heart block. Ann Rheum Dis. 2024 Oct 21;83(11):1598-600. DOI: 10.1136/ard-2024-226176http://dx.doi.org/10.1136/ard-2024-226176Gamerith GMildner FMerkel PAHarris KCooney LLim NSpiera RSeo PLangford CAHoffman GSSt Clair EWFervenza FCMonach PYtterberg SRGeetha DAmann AWolf DSpecks UStone JHKronbichler AAssociation of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission2023Ann Rheum Dis253-61Gamerith G, Mildner F, Merkel PA, Harris K, Cooney L, Lim N, Spiera R, Seo P, Langford CA, Hoffman GS, St Clair EW, Fervenza FC, Monach P, Ytterberg SR, Geetha D, Amann A, Wolf D, Specks U, Stone JH, Kronbichler A. Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission. Ann Rheum Dis. 2023 Feb;82(2):253-61. DOI: 10.1136/ard-2022-222479http://dx.doi.org/10.1136/ard-2022-222479011
Figure 1: (A) Circulating levels of sCD25, sTIM-3 and sGal-9 are higher in the active disease group (SLEDAI > 4) compared with patients in remission. Multivariable logistic regression model adjusted for age, sex, and prednisolone dose. Significant results (p<0.05) are highlighted in green, the other in orange. (B) ROC curves displaying the predictive performance of univariate logistic regression models for biomarkers sCD25 (red), sTIM-3 (black), and sGal-9 (blue) differentiate SLEDAI active vs. inactive states.