Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment.
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.
Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. barbara.fuernrohr@i-med.ac.at.|Division of Genetic Epidemiology and Division of Biological Chemistry, Innrain 80/IV, Medical University Innsbruck, 6020 Innsbruck, Austria. barbara.fuernrohr@i-med.ac.at.
Barbara G
BG
Fürnrohr
Department of Rheumatology, University Hospitals Birmingham NHS foundation trust, Edgbaston, B15 2GW Birmingham, UK. timothy.vyse@kcl.ac.uk.|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. timothy.vyse@kcl.ac.uk.
Benjamin
B
Rhodes
Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. luis.munoz@uk-erlangen.de.
Luis E
LE
Munoz
Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. kweiss@molmed.uni-erlangen.de.|Division of Molecular Immunology of the Department of Internal Medicine 3, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. kweiss@molmed.uni-erlangen.de.
Katrin
K
Weiß
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. timothy.vyse@kcl.ac.uk.
Tim J
TJ
Vyse
Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. georg.schett@uk-erlangen.de.
Georg
G
Schett
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001772:Blood Cell Count; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000097:blood / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010010:Osteoclasts / Q000166:cytology* / Q000473:pathology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016898:Interferon-alpha; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid
RANKL; interferon alpha; mycophenolate mofetil; osteoclastogenesis; systemic lupus erythematosus