Skip to main content
Article thumbnail
Location of Repository

Heterogeneity of injury in vasculitis: influence of anti neutrophil cytoplasm antibody IgG subclass and endothelial susceptibility.

By Tanya Pankhurst


This study examined IgG subclass in ANCA associated vasculitis and glomerular endothelial cell (GEC) phenotype predisposes to injury. Using the flow model, interaction of neutrophils with normal immunoglobulin subclasses was compared to interaction with subclasses of ANCA IgG. Neutrophils were captured by normal IgG3>IgG1>IgG2/IgG4. Blockade of CD32 affected IgG3, CD16, IgG1/2. Neutrophils exposed to soluble ANCA IgG1/3 adhered to cytokine-activated endothelial cells, as did IgG4, not previously thought to bind constitutively expressed CD16/CD32. Fc blockade reduced binding. GEC were compared with human umbilical vein endothelial cells. Surface VCAM-1 was reduced on GEC and GEC demonstrated reduced leukocyte capture. RNA array analysis demonstrated a reduction in the GEC gene responsible for post translational modification of VCAM-1 to a sialoglycoprotein. VCAM-1 expression by GEC may be a protective mechanism to reduce inflammatory responses, potentially disrupted in disease. ANCA subclass and endothelial phenotype are important vasculitis pathogenesis: this may be useful in designing targeted therapy reducing overall immunsuppressive load. Additionally modification of specific adhesion molecule profiles on endothelial cells may enable alteration of conditions of one vascular bed whilst reducing impact on unaffected sites

Topics: R Medicine (General), QR180 Immunology
Year: 2010
OAI identifier:

Suggested articles


  1. (1998). Chemok ines and leukocyte traffic."
  2. (1985). E xpression of organ-specific antigens on capillary endothelial cells." doi
  3. (1999). Endothelial alpha 2,6-lin ked sialic acid inhibits VCAM-1-dependent adhesion under flow conditions."
  4. (1996). Functions of dom ain 1 and 4 of vascular cell adhesion molecule-1 in alpha4 integrin -dependent adhesion under static and flow conditions are differentially regulated."
  5. (2001). Heterogenei ty of endothelial junctions is reflected by differentia l expression and specific subcellular localization of the thre e JAM family members." doi
  6. (1991). IgG Fc receptors on epithelial cells of distal tubuli and on endothelial cells in human kidney." doi
  7. (2002). IgG4 breaking the rules." doi
  8. (2006). Increased ne utrophil membrane expression and plasma level of proteinase 3 in systemic vasculitis are not a consequence of the - 564 A/G promotor polymorphism."
  9. Low ell (2007). "Convergence of immunoreceptor and integrin signaling."
  10. (2008). R enal expression of adhesion molecules in anca-associated disease." doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.