Artikel
Serum levels of soluble interleukin-2 receptor correlate with beta2-microglobulin, NT-pro BNP and high-sensitivity troponin T and may help to identify patients with clinical progress in SSc
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Autoren
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Luise Schumacher
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Rheumatologie und klinische Immunologie, Lübeck
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Sebastian Klapa
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Rheumatologie und klinische Immunologie, Lübeck; Christian-Albrechts-Universität zu Kiel, Institute of Experimental Medicine, Christian-Albrechts-University of Kiel, c/o German Naval Medical Institute, Kronshagen, Germany, Kiel
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Antje Müller
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Rheumatologie und klinische Immunologie, Lübeck
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Gabriela Riemekasten
- Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Rheumatologie und klinische Immunologie, Lübeck
| Veröffentlicht: | 31. August 2022 |
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Gliederung
Text
Introduction: Systemic sclerosis (SSc) is characterized by chronic inflammation leading to damage of the vascular endothelium and excessive collagen deposition in several target organs [1]. The interaction of interleukin 2 (IL-2) with the corresponding receptor (IL-2R) is involved in the regulation of autoimmune processes [2]. The shedding product of the IL-2R alpha chain, soluble IL-2 receptor (sIL-2R, CD25), can either reduce or enhance immune responses [2]. Previously, elevated serum levels of sIL-2R were found in the bronchoalveolar lavage of SSc patients with interstitial lung disease (SSc-ILD) as well as serologically in patients with early SSc, and thus suggested to be a biomarker for clinical development of SSc [2], [3].
Methods: To determine if serological levels of sIL-2R serve as predictor of clinical complications in SSc, sera were analysed [limited cutaneous SSc (lcSSc) n=160; diffuse cutaneous SSc (dSSc), n=137] using a sandwich ELISA. Clinical data (pulmonary fibrosis, PAH, mRSS, therapy) and serological markers (hs-CRP, NT-pro BNP, neutrophil counts, creatinine, hs-troponin T, creatinine kinase, beta2-microglobulin) were assessed at the time of serum sampling and up to 48 months after baseline. Clinical progress was defined by the need to change therapies.
Results: Patients with dSSc presented elevated levels of sIL-2R compared to all SSc (dSSc: 765±593 U/ml vs. 646±473 U/ml, p=0.0001). In SSc general, sIL-2R levels correlated with beta2-microglobulin (r=0.6161, p<0.0001, ROC-AUC:0.8428), hs-CRP (r=0.4091, p<0.0001, ROC-AUC:0.7110), NT-proBNP (r=0.2610, p<0.0001, ROC-AUC:0.6793), neutrophiles (r=0.2749, p<0.0001) and hs-troponin T (r=0.4548, p<0.0001, ROC-AUC:0.8729). Further, sIL-2R levels discriminated normal from pathological levels of hs-troponin T (sensitivity 80.0%, specificity 80.1%), these results being even more significant in patients without myositis (ROC-AUC: 0.9111; sensitivity 81.82.0%, specificity 87.85%). Using Log-rank test and Mantel-Cox proportional hazard models, we found that sIL-2R levels above 900 U/ml predicted early clinical progress in SSc within 12 months (HR: 6.20, p<0.0001).
Conclusion: In SSc, serum levels of sIL-2R could be of diagnostic value by identifying clinical progress. Its role in pathophysiology, especially regarding disease manifestations such as cardiac involvement needs to be further investigated.
Disclosures: No competing interests.
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