Abstract: SA-PO1076

The Role of Plasma Cells in Autoimmune Associated Hypertension

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Taylor, Erin, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Barati, Michelle T., University of Louisville, Louisville, Kentucky, United States
  • Powell, David W., University of Louisville, Louisville, Kentucky, United States
  • Ryan, Michael J, Univeristy of Mississippi Medical Center, Jackson, Mississippi, United States
Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by the loss of immune tolerance leading to the production of pathogenic autoantibodies, and is associated with prevalent hypertension, renal injury, and cardiovascular disease. Because long-lived plasma cells produce the majority of serum immunoglobulins (Ig) and are the primary source of autoantibodies in SLE, we hypothesized that depletion of plasma cells using the proteasome inhibitor bortezomib would lower autoantibody production and attenuate hypertension.

Methods

Thirty week old female NZBWF1 and control (NZW) mice were injected i.v. with vehicle (0.9% saline) or bortezomib (0.75 mg/kg) twice weekly for four weeks.

Results

Percentages of CD138+ intracellular-κ light chain+ plasma cells in the bone marrow were lower in bortezomib treated SLE mice compared to vehicle-treated SLE mice (1.7±0.19% vs. 0.95±0.18%, p<0.05), as assessed by flow cytometry. Circulating B and T cells were not altered after bortezomib treatment. Total plasma IgG was higher in SLE mice as compared to control mice (5.02±1.2 vs. 2.88±0.78 mg/mL, p<0.05), and were lower in SLE mice treated with bortezomib (1.5±0.5 mg/mL, p<0.05 vs. SLE-vehicle). In addition, bortezomib treatment reduced circulating anti-dsDNA IgG levels in SLE mice (1.36±0.25 vs. 0.44±0.11 OD450, p<0.01). This was associated with reduced glomerular IgG deposition in bortezomib treated SLE mice compared to vehicle treated SLE mice (1752±402 vs 916±57 fluoresence/μm2, n=5-6, p<0.05) Urinary albumin excretion was increased in SLE mice as compared to controls (16.8±10.1 vs. 0.015±0.002 mg/day,p<0.05) and was lower in bortezomib treated SLE mice (0.24±00.16 mg/day, p<0.05 vs. SLE-vehicle). Mean arterial pressure (MAP; mmHg) measured in conscious mice by carotid artery catheter was higher in SLE mice than in control mice (142±5 vs. 118±3, p<0.001). MAP was significantly lower in SLE mice treated with bortezomib when compared to vehicle treated mice (119±4 vs. 142±5, p<0.001).

Conclusion

These data suggest that production of autoantibodies by plasma cells in SLE mechanistically contribute to the pathogenesis of hypertension.

Funding

  • Other NIH Support