Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated Vasculitis.

BACKGROUND: Myeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease. METHODS: MPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN. RESULTS: Anti-CD20 mAb treatment increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell-mediated and humoral anti-MPO autoimmunity and GN. Disabling of Tregs negated the therapeutic benefit of anti-CD20 treatment. The mechanism of enhancement of Treg activity could be attributed to anti-CD20 mAb effects on inducing B cell apoptosis. Administering anti-CD20 mAb-induced apoptotic splenocytes to mice developing anti-MPO GN was as effective as anti-CD20 mAb treatment in inducing Tregs and attenuating both anti-MPO autoimmunity and GN. A nonredundant role for splenic macrophages in mediating the anti-CD20 mAb-induced immunomodulation was demonstrated by showing that administration of anti-CD20 mAb ex vivo-induced apoptotic splenocytes to unmanipulated mice attenuated autoimmunity and GN, whereas deletion of splenic marginal zone macrophages prevented anti-CD20 mAb-induced immunomodulation and treatment efficacy. Six days after administering anti-CD20 mAb to mice with murine anti-MPO GN, cell-mediated anti-MPO responses and GN were attenuated, and Tregs were enhanced, but ANCA levels were unchanged, suggesting humoral autoimmunity was redundant at this time point. CONCLUSIONS: Collectively, these data suggest that, as well as reducing humoral autoimmunity, anti-CD20 mAb more rapidly induces protective anti-MPO Treg-mediated immunomodulation by splenic processing of anti-CD20-induced apoptotic B cells.

Renal Health Benefits of Rural City Planning in Japan.

Progression of chronic kidney disease (CKD) is a substantial threat because it is associated with reduced healthy life expectancy and quality of life, and increase in economic burden. Research indicates people with nondialysis CKD often have lower physical functioning and that improvement of physical activity may contribute to maintaining renal health. Another issue with the current treatment of CKD is that the synergistic effects of rural depopulation due to aging and uncontrolled rural city sprawling will increase the number of under-served healthcare areas. To ensure the quality of renal health care, hospital integration is desirable, under the condition of reconstruction of the public transport system for physically and socially vulnerable people. Recently, medical and non-medical scientists advocate the challenge of city planning for population health. The links between city design and health such as cardiovascular disease, obesity, type 2 diabetes and mental disorders, have been widely studied, except for renal health. Based on our experience in a Kidney and Lifestyle-related Disease Center, we propose the idea that city planning be prioritized to improve renal health through two main streams: 1) Improve physical status by use of public and active transportation including daily walking and cycling; and 2) Equal accessibility to renal health services. Many countries, including Japan, have enacted plans and public policy initiatives that encourage increased levels of physical activity. We should focus on the impact of such movement on renal as well as general health.