26rhk038 10.3205/26rhk038 urn:nbn:de:0183-26rhk0386 Meeting Abstract Schröder Schröder Pauline P

Translational Lung Research Center Heidelberg (TLRC), Universitätsklinikum Heidelberg, Diagnostische und Interventionelle Radiologie, Heidelberg, Deutschland Universitätsklinikum Heidelberg, Medizinische Klinik V, Rheumatologie, Heidelberg, Deutschland

author Merkt Merkt Wolfgang W

Translational Lung Research Center Heidelberg (TLRC), Universitätsklinikum Heidelberg, Diagnostische und Interventionelle Radiologie, Heidelberg, Deutschland Universitätsklinikum Heidelberg, Medizinische Klinik V, Rheumatologie, Heidelberg, Deutschland Rheumazentrum Rheinland-Pfalz, Bad Kreuznach, 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 038 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 Experimentelle & Translationale Rheumatologie Leipzig 20260909 20260912 ET.12 TextIntroduction: We have previously shown that the potential of soluble immune complexes (sICs) to activate Fcy-receptors such as CD16 on Natural Killer (NK) cells is linked to interstitial lung disease (ILD) in anti-Scl70 positive Systemic Sclerosis (SSc). We have also shown that HLA-E expression on senescent fibroblasts mediates their immune escape and accumulation in fibrosis.Here we investigated the link between autoimmunity, sICs, NK cells and fibroblast pathology.Methods: sICs in sera were detected using a novel reporter cell assay that quantifies sICs by their ability to engage Fcy-receptors (“bioactivity”). “Neo-sICs” were generated by adding recombinant Scl70 antigen to sera from anti-Scl70 positive SSc patients. The effect of Neo-sICs on PBMCs and NK cells in mono- as wells as coculture with primary pulmonary fibroblasts was analyzed by flow cytometry.Results: We observed a significantly higher sIC bioactivity in anti-Scl70 positive SSc sera compared to anti-Scl70 negative SSc and healthy control sera. In anti-Scl70 positive sera sIC bioactivity was further enhanced by addition of Scl70 antigen. In healthy PBMCs these “Neo-sICs” activated Fcγ receptor bearing monocytes and NK cells and caused functional degranulation (Figure 1 (A) ) and release of IFN-y by NK cells. Incubation with NK cell-derived IFN-y or co-culture with sIC-activated NK cells induced an inflammatory phenotype in primary pulmonary fibroblasts and upregulated the NK cell inhibiting ligand HLA-E.Conclusion: Our results link Scl70-specific sICs and fibroblast pathology via activation of NK cells. NK cell activity and release of IFN-y have a bifold pro-fibrotic effect on fibroblasts by inducing an inflammatory phenotype and upregulating HLA-E, thus reducing their susceptibility to immune clearance (Figure 1 (B) ). 0

1 1 Figure 1: (A) Anti-Scl70 specific sICs induce activation and degranulation of NK cells in serum from anti-Scl70 pos. SSc patients (B) sIC-activated NK cells release IFN-y and induce inflammation (HLA-ABC and HLA-DR upregulation) and immune escape (HLA-E upregulation) in pulmonary fibroblasts

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