(1) Background: To date, the response of patients with rheumatoid arthritis (RA) to the
various biologic DMARD available cannot be predicted due to a lack of reliable biomarkers. Based
on our preliminary work on tmTNF reverse signaling, we developed a whole-blood assay measuring
tmTNF crosslinking-induced IL-10 production to predict the response to TNF inhibitor (TNFi) therapy.
(2) Methods: This prospective study included patients with active RA. Depending on the clinical
judgment of the attending rheumatologist, either therapy with a TNF or JAK inhibitor was initiated.
Clinical parameters and blood samples were obtained at baseline and after 8 weeks of therapy. The
blood samples were collected using a newly developed whole-blood assay based on the principle of
tmTNF reverse signalling. Subsequently, IL-10 was measured via enzyme-linked immunosorbent
assay (ELISA) technique. (3) Results: 63 patients with RA were enrolled. In fifteen patients, TNFi
therapy was initiated, while eight patients started a JAKi treatment. The cross-sectional analysis of all
patients showed a positive correlation between tmTNF crosslinking-induced IL-10 and parameters
of disease activity (CRP [r = 0.4091, p = 0.0009], DAS28 [r = 0.3303, p = 0.0082]) at baseline. In the
TNFi treatment study, IL-10 was found to be significantly higher in EULAR responders than in
non-responders (p = 0.0033). After initiation of JAKi treatment, in contrast, IL-10 induction was not
linked to response. Longitudinal analysis of the TNFi-treated patients revealed IL-10 to decrease in
responders (p = 0.04), but not in non-responders after 8 weeks of therapy. Of importance, the IL-10
production at baseline correlated inversely with TNFi response determined by DDAS28 in patients
with TNFi treatment (r = 0.5299, p = 0.0422) while no such link was observed under JAKi therapy
(p = 0.22). Receiver operation characteristics (ROC) analysis demonstrated a high performance of
tmTNF/crosslinking-induced IL-10 in predicting a TNFi therapy response according to the EULAR
criteria (AUC = 0.9286, 95% Confidence interval 0.7825–1.000, p = 0.0055). (4) Conclusions: In
this pilot investigation, we demonstrated the feasibility of a whole-blood assay measuring tmTNFinduced
IL-10 to predict clinical response to TNF inhibitor treatment. This approach might support
rheumatologists in their decision for an individually tailored RA therapy.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87528 |
| Date | 20 October 2023 |
| Creators | Krasselt, Marco, Gruz, Natalya, Pierer, Matthias, Baerwald, Christoph, Wagner, Ulf |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1003 |
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