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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC34...
From: Curr Opin Rheumatol. Author manuscript; available in PMC 2012 August 28. Published in final edited form as: Curr Opin Rheumatol. 2012 January; 24(1): 17. doi: 10.1097/BOR.0b013e32834d2d52 Copyright/License Request permission to reuse
Table 1
Models of MPO- and PR3-ANCA associated vasculitis and glomerulonephritis
Model Induction protocol Proposed Mechanism Passive anti- Anti-MPO-Ab MPO Ab transfer induced in and transferred into recipients or RAG2deficient animals). LPS primed animals had worse disease. ANCA induced neutrophil dependent on B cells and alternative activation Organs affected Lungs, kidneys Focal necrotising GN, with 5-15% crescents in RAG2 recipients and 2-6% crescents in WT recipients. GN more severe in 129 strain (42-90% crescents). MPO-ANCA MPO-immune DTH model response induced by immunisation of MPO in CFA, followed by Delayed type hypersensitivity response to planted nephrotoxic antigen, Kidney only Crescentic GN with 15-19% crescents. Dosing and timing of nephrotoxic serum critical. Needs to be replicated 9 Severity Comments/Referen ce Noticeable strain effect (needs to be replicated) and influence of MPOANCA dose and LPS priming2
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Model
Induction protocol
Proposed Mechanism
Organs affected
Severity
Comments/Referen ce
allowing neutrophil degranulation and deposition of MPO target. T cell, but not B cell dependent.
Induction of anti-MPO
Lungs, Kidney
Immunisation of NOD mice with recombinant PR3 in CFA and passive transfer of splenocytes into NODSCID mice
Lungs, kidneys
NOD-RAG did not develop disease while NODSCID did, suggesting that significant other factors apart from PR3 reactive splenocytes play a role. Needs to be replicated.20
necrotising GN recipients
Generation of chimeric human-mouse immune human CD34+stem cells to NOD SCID IL2receptor ko mice, followed by passive transfer of PR3-ANCA
Generation of myeloid and lymphoid chimerism human neutrophil and monocyte targets for PR3-ANCA
Lungs, kidneys
Mild proliferative GN
Needs to be replicated 21
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Model
Induction protocol
Proposed Mechanism
Severity
Comments/Referen ce
LAMP-2/Fim Passive transfer of H related vasculitis rabbit antibodies in WKY rats, or immunisation of WKY rats with FimH
Generation of pauci necrotising GN in passive transfer model, following binding of anti-LAMP2 antibodies to glomerular endothelium. Generation of pulmonary and renal vasculitis in FimH immunised model, associated with anti-rat LAMP2 Ab induction.
Pauci-immune
No PR3 or MPO
necrotising GN immunity. Needs to be replicated.22 with 20% crescents in passive model. Renal and lung (25% cases) involvement in immunised model.
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