Background/Purpose: 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 aimed to measure serum GM-CSF together with markers of bone metabolism in patients with AS before and after anti-TNF treatment.

Methods: The study included patients with the clinical diagnosis of AS (also fulfilling the 1984 modified NY criteria) with increased disease activity despite treatment with NSAIDs, all being eligible for treatment with a biologic DMARD. Decision for treatment with a TNF-inhibitor was made by the treating rheumatologist. 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, 5 females, median age 37 years, range 22-52) with a median disease duration of 1 year (range 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 decreased 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 baseline). Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (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.

References
1. Sen R, Kim E, Cheng E et al. A Tough Cell: The Argument for a Biomarker of Clinical and Imaging Outcomes in Spondyloarthritis: The Neutrophil Lymphocyte Ratio and the Platelet Lymphocyte Ratio [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10).
2. Crotti C, Agape E, Becciolini A et al. Targeting Granulocyte-Monocyte Colony-Stimulating Factor Signaling in Rheumatoid Arthritis: Future Prospects. Drugs. 2019 Nov;79(16):1741-1755

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-granulocyte-macrophage-colony-stimulating-factor-gm-csf-is-increased-in-patients-with-active-ankylosing-spondylitis-as-and-persists-despite-anti-tnf-treatment/