PMID- 19823088
OWN - NLM
STAT- MEDLINE
DCOM- 20100216
LR  - 20091125
IS  - 1531-6963 (Electronic)
IS  - 1040-8711 (Linking)
VI  - 22
IP  - 1
DP  - 2010 Jan
TI  - Pathogenesis of small vessel vasculitis associated with autoantibodies to 
      neutrophil cytoplasmic antigens: new insights from animal models.
PG  - 15-20
LID - 10.1097/BOR.0b013e328332c9e4 [doi]
AB  - PURPOSE OF REVIEW: Morbidity and mortality associated with current treatment 
      strategies in ANCA associated small vessel vasculitis (AASV) are unacceptably 
      high and more specific therapies will require more detailed knowledge of the 
      pathogenesis of the disease. In-vitro experiments have provided invaluable 
      insight into the molecular mechanisms of antibody action and their subcellular 
      effects; however, they may not reflect the in-vivo situation that can only be 
      assessed in animal models. RECENT FINDINGS: Rodent models provide convincing 
      evidence that myeloperoxidase (MPO) and antibodies to it can cause small vessel 
      vasculitis but the development of rodent models of anti-proteinase 3 (PR3) 
      antibody mediated injury is proving much more problematic. Insight into the 
      molecular differences of the human and mouse antigens and antibodies to them as 
      well as analysis of the molecular interaction with their binding partner(s) have 
      highlighted potential resolutions to this discrepancy. The recent 
      characterization of autoimmunity to lysosomal membrane glycoprotein-2 (LAMP-2) in 
      AASV and the possible inductions of autoantibodies to it by molecular mimicry 
      open an entirely new area for study. SUMMARY: Recent advances in the development 
      of animal models that more faithfully model the disease and the discovery of 
      novel ANCA antigens such as LAMP-2 provide new opportunities to dissect the 
      mechanisms involved in the pathogenesis of AASV.
FAU - Kain, Renate
AU  - Kain R
AD  - Institute of Clinical Pathology, Medical University of Vienna, Wahringer Gurtel, 
      Vienna, Austria. renate.kain@meduniwien.ac.at
FAU - Firmin, Dawn A
AU  - Firmin DA
FAU - Rees, Andrew J
AU  - Rees AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Curr Opin Rheumatol
JT  - Current opinion in rheumatology
JID - 9000851
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Autoantibodies)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
SB  - IM
MH  - Animals
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated 
      Vasculitis/*immunology/physiopathology
MH  - Antibodies, Antineutrophil Cytoplasmic/*metabolism
MH  - Antibody Specificity/immunology
MH  - Autoantibodies/*metabolism
MH  - Autoimmunity/*immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Lysosomal-Associated Membrane Protein 2/metabolism
MH  - Mice
MH  - Molecular Mimicry/immunology
MH  - Neutrophils/immunology/metabolism
MH  - Species Specificity
RF  - 46
EDAT- 2009/10/14 06:00
MHDA- 2010/02/17 06:00
CRDT- 2009/10/14 06:00
PHST- 2009/10/14 06:00 [entrez]
PHST- 2009/10/14 06:00 [pubmed]
PHST- 2010/02/17 06:00 [medline]
AID - 10.1097/BOR.0b013e328332c9e4 [doi]
PST - ppublish
SO  - Curr Opin Rheumatol. 2010 Jan;22(1):15-20. doi: 10.1097/BOR.0b013e328332c9e4.