New insights into the immunopathogenesis and treatment of small vessel vasculitis of the kidney.
OBJECTIVE
Glomerulonephritis is an important manifestation of small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Renal involvement in these diseases is characterized by a pauci-immune segmental necrotizing and crescentic glomerulonephritis that is strongly associated with circulating antineutrophil cytoplasmic autoantibodies. We will review recent advances in understanding the pathogenesis of antineutrophil cytoplasmic autoantibody-related renal vasculitides and innovative approaches to their treatment.


RESULTS
An experimental milestone in antineutrophil cytoplasmic autoantibody research has been reached in the past year. Using an innovative mouse model, investigators from the University of North Carolina in Chapel Hill have recently acquired robust data supporting the pathogenic role of antineutrophil cytoplasmic autoantibodies in the glomerulonephritis and small vessel vasculitis, analogous to those seen in microscopic polyangiitis and Wegener granulomatosis. Novel immunosuppressive approaches have been examined including preliminary studies using biologic agents, such as antagonists of tumor necrosis factor and monoclonal antibodies to B lymphocytes.


CONCLUSIONS
Recent insights into the pathogenesis of antineutrophil cytoplasmic autoantibody-related vascular injury and the availability of new biologic, immune response modifiers to complement standard chemical immunosuppressive agents offer exciting new prospects for investigation in the management of patients with small vessel renal vasculitides.
Langford
Carol A
CA
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1818, USA.
Balow
James E
JE
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069283:Rituximab; D014657:Vasculitis / Q000209:etiology* / Q000276:immunology / Q000628:therapy
D000276:Adjuvants, Immunologic; D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D008727:Methotrexate