CD48 as a novel molecular target for antibody therapy in multiple myeloma

Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM.     

Pulmonary capillaritis leading to alveolar hemorrhage in a juvenile idiopathic arthritis patient: first description

Juvenile idiopathic arthritis (JIA) is characterized by the typical joint involvement and some patients have extra-articular lesions, such as uveitis and pleuritis. However, until this date, no case of alveolar hemorrhage in JIA has been described. Herein, the authors describe a case of a male patient, 33?years old diagnosed as polyarticular JIA who had a dramatic evolution with alveolar hemorrhage secondary to pulmonary capillaritis. He received intravenous immunoglobulin and pulse therapies with glucocorticoid and cyclophosphamide with a satisfactory outcome. In addition, the authors review this important pulmonary complication in rheumatic diseases.