Several studies suggest a link between autoimmunity and
essential hypertension in humans. However, whether autoimmunity can drive the development of
hypertension remains unclear. The
autoimmune disease systemic lupus erythematosus is characterized by
autoantibody production, and the prevalence of
hypertension is increased markedly in this patient population compared with normal healthy women. We hypothesized that preventing the development of autoimmunity would prevent the development of
hypertension in a mouse model of lupus. Female lupus (NZBWF1) and control mice (NZW) were treated weekly with anti-CD20 or
immunoglobulin G antibodies (both 10 mg/kg, IV) starting at 20 weeks of age for 14 weeks. Anti-CD20
therapy markedly attenuated lupus
disease progression as evidenced by reduced CD45R+ B cells and lower
double-stranded DNA autoantibody activity. In addition, renal injury in the form of urinary
albumin, glomerulosclerosis, and tubulointerstitial
fibrosis, as well as tubular injury (indicated by renal cortical expression of
neutrophil gelatinase-associated lipocalin) was prevented by anti-CD20
therapy in lupus mice. Finally, lupus mice treated with anti-CD20 antibody did not develop
hypertension. The protection against the development of
hypertension was associated with lower renal cortical
tumor necrosis factor-α expression, a
cytokine that has been previously reported by us to contribute to the
hypertension in this model, as well as renal cortical
monocyte chemoattractant protein-1 expression and circulating T cells. These data suggest that the development of autoimmunity and the resultant increase in renal
inflammation are an important underlying factor in the prevalent
hypertension that occurs during
systemic lupus erythematosus.