Antibody glycosylation and bone loss in cancer

Multiple myeloma is a cancer caused by accumulation of malignant plasma cells in the bone marrow. Nearly all patients develop a severe osteolytic bone disease causing pain and fractures. The myeloma cells secrete immunoglobulins (Igs), and the presence of monoclonal Igs (M-component) in the patients’ serum is the main diagnostic criteria. The high concentration of Igs in the circulation may lead to renal failure, but except for that, the patophysiological effect of the Igs is not well characterized. In this project we demonstrated that Igs obtained from bone marrow plasma of multiple myeloma patients influence bone cell differentiation, and that the M-component can promote bone destruction. We further found that the effect is caused by changes in antibody glycosylation, and that we can reduce bone destruction in a mouse model for multiple myeloma by modifying antibody glycosylation. Results from this research proposal have led to a completely new understanding of why patients with multiple myeloma loose bone and have identified new targets for treatment.

Prosjektet har bidratt til en ny forståelse av årsaken til beinsykdommen ved myelomatose. Vi har identifisert nye angrepspunkter for behandling som på sikt vil kunne føre til endring av hvordan pasienter behandles.

Multiple myeloma is a cancer caused by accumulation of malignant plasma cells in the bone marrow. Nearly all patients develop a severe osteolytic bone disease causing extreme pain and fractures. The myeloma cells secrete immunoglobulins (Igs), and the presence of monoclonal Igs in the patients? serum is the main diagnostic criteria. The extremely high concentration of Igs in the circulation (> 30g/L), may lead to renal failure, but except for that, no patophysiological effect of the Igs have so far been described. However, we have now found that Igs obtained from bone marrow plasma of patients with bone disease can promote osteoclast differentiation in vitro, whereas Igs obtained from patients without bone disease do not. In this project we aim to determine the role of immunoglobulins for multiple myeloma disease progression. The findings from this research proposal may lead to a completely new understanding of why patients with multiple myeloma loose bone and may identify new targets for treatment.