Artikel
Bioactive soluble immune complexes in serum and synovial fluid from patients with rheumatoid arthritis
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Autoren
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Ivana Andreeva
- Innere Medizin V: Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg
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Philipp Kolb
- Uniklinik Freiburg, Institut für Virologie, Freiburg im Breisgau; Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg, Freiburg im Breisgau
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Hanns-Martin Lorenz
- Innere Medizin V: Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg
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Lars-Oliver Tykocinski
- Innere Medizin V: Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg
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Wolfgang Merkt
- Innere Medizin V: Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg
| Veröffentlicht: | 31. August 2022 |
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Gliederung
Text
Introduction: The prevalence and significance of soluble immune complexes (sICs) in body liquids in healthy individuals and patients with rheumatic diseases is unknown. Potentially, sICs contribute to inflammation in rheumatoid arthritis (RA)[1]. Methods to detect and quantify sICs have been limited by technical challenges. These methods either rely on isolation of sICs with intrinsic low specificity preventing investigations of their direct functionality. Alternatively, diagnostic assays quantify sICs indirectly via their effect on complement factors. However, sICs mediate many of their effects via an alternative pathway – the activation of Fcɣ-receptors. A sensitive and specific method for quantifying bioactive sICs has the potential to serve as a biomarker and allow for investigations of their effect on Fcɣ-receptor-bearing cells.
Methods: We used a novel reporter assay based on mouse BW5147 cells stably expressing the human Fcɣ-receptor-IIIa (CD16)[2]. The assay can be used to quantify the amount of sICs in biological samples. It also determines the functionality of sICs by their ability to directly activate CD16-signaling. Reporter and parental (non-transfected) cells were incubated with biological samples and mouse IL-2 was quantified by ELISA as a surrogate of CD16-activation by sICs.
Results: The reporter cell assay was successfully implemented and sICs were detected in multiple human samples. We screened sera and synovial fluids from patients with RA and compared the degree of sICs with clinical parameters. We also compared RA patients with healthy controls and other rheumatological diseases. We showed that synovial fluid from RA and sera from patients with systemic lupus erythematosus contained the highest amount of sICs.
Conclusion: Both human serum and synovial fluid can contain bioactive sICs. While the direct effect of sICs on human immune cells remains to be elucidated, the varying amounts of sICs between patients, tissues and diseases opens the possibility for usage as a new biomarker in immune-mediated diseases.
Disclosures: The authors declare that they have no conflict of interest.
References
- 1.
- Zhao S, Grieshaber-Bouyer R, Rao DA, Kolb P, Chen H, Andreeva I, Tretter T, Lorenz HM, Watzl C, Wabnitz G, Tykocinski LO, Merkt W. JAK inhibition prevents the induction of pro-inflammatory HLA-DR(+) CD90(+) RA synovial fibroblasts by IFN. Arthritis Rheumatol. 2021.
- 2.
- Chen H, Maul-Pavicic A, Holzer M, Huber M, Salzer U, Chevalier N, Voll RE, Hengel H, Kolb P. Detection and functional resolution of soluble immune complexes by an FcγR reporter cell panel. EMBO Mol Med. 2022 Jan 11;14(1):e14182. DOI: 10.15252/emmm.202114182
