Imatinib suppresses cryoglobulinemia and secondary membranoproliferative glomerulonephritis

J Am Soc Nephrol. 2009 Jan;20(1):68-77. doi: 10.1681/ASN.2008010036. Epub 2008 Nov 19.

Abstract

Imatinib is a receptor tyrosine kinase inhibitor that blocks the activity of c-Abl, c-Kit, and PDGF receptors. We tested the protective effects of imatinib in thymic stromal lymphopoietin transgenic mice, a model of cryoglobulinemia and associated membranoproliferative glomerulonephritis (MPGN), in which some glomerular manifestations likely result from PDGF receptor activation. Surprising, administration of imatinib beginning at weaning suppressed production of cryoglobulin, attenuating both the renal injury and systemic features of cryoglobulinemia. Flow cytometry suggested that inhibition of B cell development in the bone marrow likely caused the reduction in cryoglobulin production. In addition, administration of imatinib to thymic stromal lymphopoietin transgenic mice with established MPGN also diminished cryoglobulin production and reversed the renal and systemic lesions. These data suggest that treatment with imatinib may be a novel therapeutic approach for cryoglobulinemia and MPGN in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Benzamides
  • Complement C3 / metabolism
  • Cryoglobulinemia / drug therapy*
  • Cryoglobulinemia / immunology
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / physiology
  • Female
  • Glomerulonephritis, Membranoproliferative / drug therapy*
  • Glomerulonephritis, Membranoproliferative / immunology
  • Imatinib Mesylate
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Transgenic
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*

Substances

  • Benzamides
  • Complement C3
  • Cytokines
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • thymic stromal lymphopoietin