Humoral immune system activation promotes the development of hypertension

Abstract

Circulating autoantibodies are elevated in patients with essential hypertension suggesting the possibility of humoral immune system activation. Whether humoral immunity underlies the pathogenesis of hypertension is unclear. We hypothesized that humoral immune suppression (B cell depletion) would prevent the development of hypertension in a mouse model of the autoimmune disease systemic lupus erythematosus (SLE). Female SLE (NZBWF1) and control mice (NZW) were treated weekly with anti‐CD20 (10 mg/kg, Genentech) or vehicle (anti‐IgG) starting at 20, 26, and 30 weeks of age and ending at 34 weeks. Anti‐CD20 treatment reduced spleen weight in all groups regardless of treatment duration. Mean arterial pressure (MAP; mmHg) was higher in SLE mice compared to controls in all groups [(20 weeks; 134±1 vs 115±3, p<0.01); (26 weeks; 139±5 vs 116±2, p<0.001); (30 weeks; 138±2 vs 117±6, p<0.001)]. Anti‐CD20 did not alter MAP in SLE mice treated from 26 (131±3) or 30 (135±4) weeks of age. However, MAP was lower in SLE mice treated with anti‐CD20 starting at 20 weeks of age (120±3; p=0.01). Anti‐CD20 did not affect MAP in any control group. These data suggest that suppression of humoral immunity early in disease progression, but not later, can prevent the development of hypertension and supports the idea of autoimmunity as an underlying mechanism.AHA4350019/5T32HL105324, HL085907/HL092284/HL085907S1/UMMC‐IRSP, HL051971