Artikel
Serum Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF) is increased in patients with active ankylosing spondylitis (AS) and persists despite anti-TNF treatment
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Autoren
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Charalampos Papagoras
- First Department of Internal Medicine and Laboratory of Molecular Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis
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Styliani Tsiami
- Rheumazentrum Ruhrgebiet, Herne; Ruhr-Universität Bochum, Bochum
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Akrivi Chrysanthopoulou
- First Department of Internal Medicine and Laboratory of Molecular Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis
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Ioannis Mitroulis
- First Department of Internal Medicine and Laboratory of Molecular Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis
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Xenofon Baraliakos
- Rheumazentrum Ruhrgebiet, Herne; Ruhr-Universität Bochum, Bochum
| Veröffentlicht: | 31. August 2022 |
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Gliederung
Text
Introduction: There is increasing evidence of the pathogenetic role of monocytes and neutrophils in AS, while the neutrophil-to-lymphocyte ratio correlates with disease activity [1]. Granulocyte-Monocyte Colony-Stimulating-Factor (GM-CSF) is a growth factor for both myeloid lineages and a potent pro-inflammatory cytokine activating myeloid cells, including pro-inflammatory M1-macrophage polarization, production of TNF and other cytokines, and promoting osteoclastogenesis [2]. It signals through the JAK-STAT pathway. We measured serum GM-CSF together with markers of bone metabolism in AS patients before and after anti-TNF treatment.
Methods: The study included AS patients with increased disease activity, all being eligible for treatment with a bDMARD. Healthy donors were sampled as controls. Serum was collected before (baseline, BL) and after 4-6 months (follow-up, FU) of anti-TNF treatment and the following molecules were measured using ELISA: GM-CSF, Sclerostin (SOST) and Dickkopf-1 (Dkk-1).
Results: Twelve patients with AS (7 males, median age 37 years (22-52)) with a median disease duration of 1 year (0.5-25) and 16 age- and sex-matched controls were included. At BL, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7. At FU the mean BASDAI decreased to 4.1±1.7 and ASDAS to 2.2±0.6. At BL, AS patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not significantly affect GM-CSF, Dkk-1 or SOST levels (p>0.05 for all comparisons at FU vs BL). Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at BL (r=0.61, p=0.039), negatively with age (r=-0.68, p=0.018), but not with disease duration (r=-0.27, p=0.400). No correlations were identified between bone markers (Dkk-1, SOST) and GM-CSF or disease activity indices.
Conclusion: GM-CSF is increased in patients with active AS, particularly in younger ages, and strongly correlates with disease activity, but not with disease duration. In contrast, TNF-inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway in AS that could be responsible for residual inflammation during TNF blockade, but also explain the efficacy pathway of treatment with JAK-inhibitors.
Disclosures: N/a.
References
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