title: Preventing autoimmunity protects against the development of hypertension and renal injury.
abstract: 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.
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Keisa W
authors.initials: KW
authors.lastname: Mathis
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Flynn
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Christine
authors.initials: C
authors.lastname: Maric-Bilkan
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
authors.affiliation: From the Departments of Physiology and Biophysics (K.W.M., E.R.F., C.M.-B., M.J.R.), Obstetrics and Gynecology (K.W.), and Pharmacology and Toxicology (B.L.), University of Mississippi Medical Center, Jackson. mjryan@umc.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ryan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology; D002374:Catalase / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D000075222:Essential Hypertension; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006973:Hypertension / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000293:injuries; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008212:Lymphocyte Depletion; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D018951:Antigens, CD20; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D017493:Leukocyte Common Antigens
keywords: B-lymphocytes; T-lymphocytes; autoantibodies; pressure