Imatinib suppresses cryoglobulinemia and secondary membranoproliferative glomerulonephritis.
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.
Iyoda
Masayuki
M
Department of Pathology, University of Washington, 1959 NE Pacific Avenue, Box 357470, Seattle, WA 98195, USA.
Hudkins
Kelly L
KL
Becker-Herman
Shirly
S
Wietecha
Tomasz A
TA
Banas
Miriam C
MC
Guo
Shunhua
S
Meyer-Bahlburg
Almut
A
Kowalewska
Jolanta
J
Liu
Gang
G
Ziegler
Steven F
SF
Rawlings
David J
DJ
Alpers
Charles E
CE
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001549:Benzamides; D003176:Complement C3 / Q000378:metabolism; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000502:physiology; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000276:immunology; D000068877:Imatinib Mesylate; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D000094632:Thymic Stromal Lymphopoietin
D001549:Benzamides; D003176:Complement C3; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse