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Abstract: TH-PO846

The Role of MPO, Plasma Cell, and CD20 in the Pathogenesis of Human MPO-ANCA-Associated Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kawashima, Soko, Kyorin University School of Medicine, Mitaka, ToKyo, Japan
  • Kaname, Shinya, Kyorin University School of Medicine, Mitaka, ToKyo, Japan

Group or Team Name

  • First Department of Internal Medicine, Kyorin University School of Medicine
Background

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis (GN) is characterized by pauci-immune necrotizing glomerulonephritis. We reported that MPO and immune complexes composed of MPO-anti MPO antibody may play some direct roles in the pathogenesis of glomerular capillary injuries in the early phase of the disease. Previous studies have suggested involvement of infiltrated macrophages and lymphocytes. Here we investigated a possible role of MPO-positive cells, plasma cells, CD20-positive B-lymphocytes in the development of MPO-ANCA- associated GN.

Methods

Patients with ANCA-associated vasculitis (AAV) were diagnosed according to the definition of the 2012 Chapel Hill Consensus Conference and the 1990 American College of Rheumatology classification criteria. Using renal biopsy specimen including more than 10 glomeruli that were obtained from 20 patients with MPO-ANCA-associated GN, we analyzed the extent of glomerular infiltration of CD20-positive cells and plasma cells as well as extracellular and cellular deposition of MPO by immunohistochemistry. The colocalization of MPO and plasma cells / CD20 cells was also examined by double staining for MPO and CD20 using immunofluorescence.

Results

CD20-positive cells were found only in 5 of the 151 glomeruli (0.67%) and mainly located in the peritubular capillaries around the glomeruli with active lesions. In contrast, plasma cells were frequently observed in 124/151 glomeruli (82.1%) of the early phase and located mainly in the endocapillary proliferative lesions and extra-capillary crescentic lesions. MPO exists along the glomerular capillary walls near the infiltrated MPO-positive neutrophils in the early phase. No colocalization of CD20-positive cells with MPO-positive cells / MPO deposition was observed, but MPO was occasionally stained in plasma cells.

Conclusion

These results suggest that plasma cells, rather than CD-20 positive cells, may play some roles possibly through MPO in the pathogenesis of human MPO-ANCA-associated glomerulonephritis.