Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
In Situ Immune Complex (MPO-anti MPO antibody) and Complement 3 cause Glomerular Capillary Injury in Human MPO-ANCA Associated Glomerulonephritis.
Kawashima, Soko, Arimura, Yoshihiro, Komagata, Yoshinori, Kaname, Shinya, Yamada, Akira
Pauci-immune necrotizing glomerulonephritis(NCGN) is often seen in a patient of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. MPO-ANCA has been thought to be involved in the activation of neutrophils in the pathogenesis of NCGN. Recent studies suggest that immunoglobulins precipitated on the glomerular capillaries might play some role in the pathogenesis of MPO-ANCA associated GN. Here, we investigated a possible role of MPO, IgG, complements and MPO-positive cells in the pathogenesis of MPO-ANCA associated GN.
Renal specimen including 317 glomeruli obtained from 20 patients with MPO-ANCA associated GN were analyzed. Glomerular infiltration of MPO-positive cells, deposition of extracellular MPO and endothelial cell injury were analyzed and the number of infiltrating MPO-positive cells was scored in each glomerulus, especially in early stage of the disease. Colocalization of MPO, IgG, C3 and CD34 deposition was analyzed. Immunofluorescence staining for triple staining (MPO, IgG and CD34) were performed for samples of renal biopsies.
All of 20 patients showed a weak but significant staining for IgG (pauci-immune GN), which was often accompanied by MPO deposition along the glomerular capillary walls. Double positive (MPO & IgG) deposition was detected in 45 glomeruli (14%) mainly with low activity and chronicity. Double positive (MPO & C3) deposition was detected in 41glomeruli (13%) mainly with low activity and chronicity. Triple positive (MPO, IgG & C3) deposition was detected in 15 glomeruli (5%) mainly with low activity and chronicity. CD34 staining was lost around the area where MPO and IgG were detected, suggesting the endothelial injury may be induced by MPO- and IgG-associated pathogenic mechanism. Deposition of MPO, IgG and C3 was observed along the glomerular capillary walls predominantly in the early stage of MPO-ANCA associated GN.
These results indicate that not only the activation of neutrophils, but also MPO and the immune complexes composed of MPO-anti MPO antibody may play some direct roles in the pathogenesis of glomerular capillary injury in the early phase of human MPO-ANCA associated GN.
To cite this abstract, please use the following information:
Kawashima, Soko, Arimura, Yoshihiro, Komagata, Yoshinori, Kaname, Shinya, Yamada, Akira; In Situ Immune Complex (MPO-anti MPO antibody) and Complement 3 cause Glomerular Capillary Injury in Human MPO-ANCA Associated Glomerulonephritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :793