Clonotypic B cells circulating in patients with multiple myeloma (MM) express CD20, and it has been suggested that these cells may be clonogenic. Furthermore, 20% of patients with MM express CD20 on their bone marrow plasma cells (BMPCs). Therefore, the authors began a phase II clinical study to determine the activity of the anti-CD20 monoclonal antibody rituximab in MM patients. Nineteen previously treated MM patients received 375 mg/m2 rituximab per week for 4 weeks. Three months after initiation of treatment, patients were assessed for response and received a second course of therapy if their disease was stable (SD) or they achieved a partial response (PR). Six of 19 (32%) patients had either a PR (n = 1) or SD (n = 5), with a median time to treatment failure of 5.5 months (mean, 10.3 months; range, 3-27+ months). All six patients who had a PR or SD had CD20+ BMPC. Overall, rituximab therapy was well tolerated. Because most patients with MM poorly express CD20 on their BMPCs, the authors evaluated agents for their ability to induce CD20 expression and thereby facilitate rituximab binding on MM cells. These studies show that interferon-gamma (IFN-y) induced CD20 expression on MM BMPCs, MM B cells, and healthy donor BMPCs. In contrast, CD20 expression on chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, healthy donor B cells, and progenitor cells was unaffected by IFN-y. Rituximab binding to the BMPCs of MM patients was also increased after culture with pharmacologically attainable levels of IFN-gamma (1-100 U/mL). In conclusion, these studies suggest that MM patients with CD20+ BMPCs may benefit from rituximab therapy. Furthermore, IFN-gamma induces CD20 expression on MM BMPCs and B cells and facilitates rituximab binding to MM BMPCs, providing the rationale for clinical trials to examine its use with CD20-directed serotherapies in MM.
Guinea pigs with a total deficiency of the fourth component of complement (C4) have been discovered. There was no evidence for the presence of a C4 inhibitor in the serum of these animals. Mating studies indicate that C4 deficiency is transmitted as a simple autosomal recessive trait. A colony of these animals is being established at the National Institutes of Health. They will provide an opportunity to more precisely define the role of complement in immune phenomena and the defense against disease.
Abstract. The data presented demonstrate linkage between the major histocompatibility locus of inbred strain 2 guinea pigs and a "specific immune response gene," the PLL gene, which controls responsiveness to poly-L-lysine and hapten conjugates of this polypeptide in these animals. This finding extends to another species and to a different immune system the linkage observed in mice between the H2 locus and specific immune response genes at the Ir-1 locus. The general significance of the linkage of specific immune response genes to histocompatibility loci is discussed.
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