OBJECTIVE: Glucocorticoids (GCs) are among the most frequently used drugs for the treatment of rheumatoid arthritis (RA). Unfortunately, up to 30% of patients with RA fail to respond to the treatment. We investigated the hypothesis that patients with RA who did not respond to GC treatment have steroid-resistant peripheral blood mononuclear cells (PBMCs). METHODS: Forty-four patients with RA were enrolled in the study. PBMCs were isolated from blood samples. The effect of methylprednisolone (MP) on the proliferation of stimulated cells was measured. After taking the blood samples, 10 days of MP therapy (20 mg i.v.) was started, in order to classify the patients into either a GC-sensitive (RA/GCS) or a GC-resistant (RA/GCR) group. RESULTS: A quarter of our patients did not show any improvement after short-term GC therapy and were assigned to the RA/GCR group. The inhibition of PBMC proliferation after MP treatment was significantly lower in the RA/GCR as compared to the RA/GCS group. CONCLUSION: Based on the close relationship between clinically observed GC resistance and a diminished response of PBMCs to MP treatment, we conclude that measurement of the steroid sensitivity of PBMCs may be a useful tool in predicting the therapeutic effect of GC in patients with RA.
OBJECTIVE: Glucocorticoids (GCs) are among the most frequently used drugs for the treatment of rheumatoid arthritis (RA). Unfortunately, up to 30% of patients with RA fail to respond to the treatment. We investigated the hypothesis that patients with RA who did not respond to GC treatment have steroid-resistant peripheral blood mononuclear cells (PBMCs). METHODS: Forty-four patients with RA were enrolled in the study. PBMCs were isolated from blood samples. The effect of methylprednisolone (MP) on the proliferation of stimulated cells was measured. After taking the blood samples, 10 days of MP therapy (20 mg i.v.) was started, in order to classify the patients into either a GC-sensitive (RA/GCS) or a GC-resistant (RA/GCR) group. RESULTS: A quarter of our patients did not show any improvement after short-term GC therapy and were assigned to the RA/GCR group. The inhibition of PBMC proliferation after MP treatment was significantly lower in the RA/GCR as compared to the RA/GCS group. CONCLUSION: Based on the close relationship between clinically observed GC resistance and a diminished response of PBMCs to MP treatment, we conclude that measurement of the steroid sensitivity of PBMCs may be a useful tool in predicting the therapeutic effect of GC in patients with RA.
Authors: Rogier A Quax; Laura Manenschijn; Jan W Koper; Johanna M Hazes; Steven W J Lamberts; Elisabeth F C van Rossum; Richard A Feelders Journal: Nat Rev Endocrinol Date: 2013-10-01 Impact factor: 43.330
Authors: Stefan M Gold; Manda V Sasidhar; Venu Lagishetty; Rory D Spence; Elizabeth Umeda; Marina O Ziehn; Thorsten Krieger; Karl-Heinz Schulz; Christoph Heesen; Martin Hewison; Rhonda R Voskuhl Journal: J Clin Endocrinol Metab Date: 2012-06-01 Impact factor: 5.958
Authors: Christopher Burnsides; Jacqueline Corry; Jacob Alexander; Catherine Balint; David Cosmar; Gary Phillips; Jeanette I Webster Marketon Journal: J Inflamm Res Date: 2012-08-22
Authors: Rogier A M Quax; Jan W Koper; Pascal H P de Jong; Ramona van Heerebeek; Angelique E Weel; Anne M Huisman; Derkjen van Zeben; Frank H de Jong; Steven W J Lamberts; Johanna M W Hazes; Richard A Feelders Journal: Arthritis Res Ther Date: 2012-08-24 Impact factor: 5.156