High Blood Pressure in Lupus-like Disease in Mice May Be Caused by White Blood Cells

Mycophenolate mofetil (MMF) was tested in laboratory mice with a systemic lupus erythematosus (SLE)-like disease, and was found to lower the animals’ blood pressure, levels of autoantibodies, and the number of specific white blood cells called B-lymphocytes. Patients with SLE often have high blood pressure, which may be caused by B-lymphocytes, the study reports.

The study, “Immunosuppression With Mycophenolate Mofetil Attenuates Hypertension in Experimental Model of Autoimmune Disease,” was recently published in the Journal of the American Heart Association.

SLE is a disease in which antibodies attack and injure the body’s own tissues by mistake. These are called autoantibodies. In SLE, autoantibodies are thought to be responsible for causing ongoing injury to the kidneys, skin, joints, and brain seen in patients with the disease. Hypertension, or high blood pressure, is often also observed in SLE patients.

In the study, researchers set out to determine whether B-cells, the white blood cells that produce antibodies, play a role in causing high blood pressure in SLE.

The team treated mice with SLE-like disease with MMF and measured the numbers of active B-cells in the blood, the levels of autoantibodies, and the mean arterial pressure (MAP), or blood pressure in the arteries.

They found that the numbers of B-cells in the animals dropped after four weeks of treatment with MMF, but rose again after eight weeks. Still, MAP remained much lower in MMF-treated mice, and autoantibodies increased only slightly, whereas they were greatly increased in mice with SLE not treated with MMF. Moreover, blood pressure was close to normal in MMF-treated mice.

The researchers hypothesized that the drop in B-cells after the four weeks of treatment had the long-term effects of halting the increase in autoantibodies and keeping blood pressure low.

“In the present study, MMF treatment had an effect on circulating B-lymphocytes, anti-dsDNA autoantibody production, renal injury, and hypertension,” the researchers wrote. “Based on the data from this study and previous studies by our laboratory, we believe that autoreactive B cells and pathogenic autoantibodies mechanistically contribute to the pathogenesis of hypertension during SLE.”

“MMF is well established as an option for both induction and maintenance therapy in patients with SLE, and it may have the added benefit of helping to control blood pressure by depleting B cells and lowering autoantibody production,” the team concluded.

“Hypertension affects a significant portion of SLE patients, and current clinical data suggest that patients with SLE have an extremely high risk of cardiovascular disease, making rigorous blood pressure control (ie, <130/80 mm Hg) of paramount importance in this patient population.”