FGF-2 and VEGF-A are potential serologic biomarkers for response to treatment with intravenous methylprednisolone in patients with Graves’ orbitopathy
Author: Gijsbert Hötte
Base Hospital / Institution: Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands
Rapid fire oral presentation
Abstract ID: 24-223
Purpose
to identify potential biomarkers related to disease activity, severity and response to intravenous methylprednisolone (IVMP) in patients with Graves’ orbitopathy (GO). We additionally aimed to identify proteins associated with high thyroid-stimulating immunoglobulin (TSI) levels
Methods
Inflammatory serum proteome was determined with a targeted proteomics approach of 368 proteins (Olink) in biobank serum samples from 111 patients with GO. Differentially expressed proteins (DEP) were defined as Log2-fold change of 0.5 and a false discovery rate (FDR)-adjusted p-value of < 0.01. TSI levels were measured with a bridge-based TSI binding assay. Severity (mild, moderate-to-severe or severe), activity (clinical activity score [CAS]) and response to IVMP were recorded retrospectively
Results
In patients with high TSI levels (cut-off 3.01 IU/L), the expression of NPPC was significantly higher, while PSPN was lower. No DEP were identified in relation to disease activity or severity. Similarly, the Olink panel did not reveal DEP in relation to IVMP response after FDR-correction, although this may have been due to the relatively low numbers (22 responders vs 16 non-responders). Based on their mechanistic effects, several of the top ranked proteins identified from the Olink analysis prior to FDR-correction are potentially relevant mediators for treatment response. Further evaluation of six selected proteins using Luminex assay or ELISA indeed showed increased levels of FGF-2 and VEGF-A in non-responders, while CCL3, NPPC, NT-proCNP and CCL5 did not differ according to IVMP response. For VEGF-A, ROC analysis showed an area under the curve (AUC) of 77.3% for identifying responders. With Youden’s index, a cut-off value of 66.5 pg/mL was associated with a sensitivity of 77.3% and specificity of 75%. For FGF-2, the AUC was 71.3% and a cut-off value of 7.2 pg/mL displayed a 95.5% sensitivity and 50% specificity
Conclusion
Our study shows that VEGF-A and FGF-2 serum levels are potential biomarkers for response to treatment with IVMP in patients with GO. Moreover, NPPC levels are increased in patients with high TSI levels
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Martijn | Kolijn | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
| Maaike | De Bie | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
| Ronald | De Keizer | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
| Martin | Van Hagen | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
| Dion | Paridaens | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
| Willem | Dik | Dept. of orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands |
