RESUMO
Antibodies against the B cell-specific antigens CD20 and CD19 have markedly improved the treatment of B cell-derived lymphoma and autoimmune diseases by depleting malignant and autoreactive B cells. However, since CD20 and CD19 are also expressed on healthy B cells, such antibodies lack disease specificity. Here, we optimize a previously developed concept that uses bispecific antibodies to induce apoptosis selectively in malignant and autoreactive B cells that express the death receptor CD95. We describe the development and characterization of bispecific antibodies with CD95xCD20 and CD95xCD19 specificity in a new IgG-based format. We could show that especially the CD95xCD20 antibody mediated a strong induction of apoptosis in malignant B cells in vitro. In vivo, the antibody was clearly superior to the previously used Fabsc format with identical specificities. In addition, both IgGsc antibodies depleted activated B cells in vitro, leading to a significant reduction in antibody production and cytokine secretion. The killing of resting B cells and hepatocytes that lack CD95 and CD20/CD19, respectively, was marginal. Thus, our results imply that bispecific anti-CD95 antibodies in the IgGsc format are an attractive tool for a more selective and efficient depletion of malignant as well as autoreactive B cells.
RESUMO
The case of a 32-year-old female with ulcerative colitis who developed severe papulopustular dermatitis while undergoing treatment with the Janus kinase (JAK) inhibitor tofacitinib. Despite intensive topical therapy, treatment with oral corticosteroids and oral doxycycline was unable to achieve sufficient improvement. Hence, tofacitinib treatment needed to be discontinued. It is well known that the class of JAK inhibitors can cause infectious and allergic cutaneous side effects. However, sterile papulopustular dermatitis as a side-effect has rarely been reported to date.