Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment

International Journal of Molecular Sciences

Barbara G. Fürnrohr¹  Benjamin Rhodes³  Luis E. Munoz¹  Katrin Weiß¹  Tim J. Vyse²  Georg Schett¹  Chak-Sing Lau⁴ 

[1] Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany; E-Mails:;Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King’s College London, Great Maze Pond, SE1 9RT London, UK; E-Mail:;Department of Rheumatology, University Hospitals Birmingham NHS foundation trust, Edgbaston, B15 2GW Birmingham, UK; E-Mail:Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;

关键词: osteoclastogenesis;    mycophenolate mofetil;    interferon alpha;    systemic lupus erythematosus;    RANKL;   

DOI  :  10.3390/ijms160818825

来源: mdpi

【 摘 要 】

Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.