Mononuclear cell activation and decreased renal function in IgA nephropathy with crescents

Abstract

Our previous immunohistologic studies with monoclonal antibodies (mAb) showed that glomerular and interstitial accumulations of mononuclear cells (MNC) were common features of many types of proliferative glomerulonephritis, especially crescentic glomerulonephritis. The current study examined a series of patients with crescentic IgA disease, since IgA disease in general has a highly variable course and the presence of crescents is one indicator of likely progression to end-stage renal failure. We compared the intraglomerular and interstitial infiltrates within biopsies from patients with crescentic IgA nephropathy (N = 5) versus those with noncrescentic IgA (N = 18), or normal controls (N = 10). Few leucocytes were found within glomeruli of normal (2.4 +/- 0.7 cells/glomerular cross section) (mean +/- SEM) or noncrescentic IgA disease biopsies (3.8 +/- 0.7), and no activated MNC bearing receptors for interleukin-2 (IL-2R) were detected. By contrast, in crescentic IgA disease, glomerular leucocytes were increased (5.1 +/- 0.6, P less than 0.01), due to increased monocyte (3.1 +/- 0.9, P less than 0.01) and T cell (1.4 +/- 0.4, P less than 0.01) infiltration, and IL-2R + MNC were then observed (1.2 +/- 0.5, P less than 0.05). Studies of interstitial cells showed small numbers of leucocytes within normal kidneys (101 +/- 16/mm2). Biopsies from noncrescentic IgA disease showed a fivefold increase in interstitial MNC infiltration (total leucocytes 565 +/- 105/mm2, P less than 0.01), due to an influx of T cells (283 +/- 59/mm2, P less than 0.01) and monocytes (120 +/- 32/mm2, P less than 0.01), and including a mean of 20% IL-2R+ MNC (114 +/- 29/mm2, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of Leukocyte Infiltration in Membranous Nephropathy with Segmental Glomerulosclerosis

“…2). These findings in MN+GS suggest that cell infiltration in the interstitium may be induced by delayed-type hypersensitivity as reported in several experimental and human glomerular diseases [13, 25, 26, 27, 28]. Namely, Mo/Mφ accumulated in GS may partly infiltrate the interstitium or release cytokines as postulated in other immune system mediated glomerulopathies [27, 29, 30].…”

Characteristics of Polymeric λ-IgA Binding to Leukocytes in IgA Nephropathy

“…These findings have important pathologic significance in IgAN, suggesting the migration and/or sequestration of leukocytes with predominant -IgA in the mononuclear phagocytic system or inflammatory tissues. Prominent infiltration of mononuclear cells is frequently detected in renal biopsies from patients with IgAN (10,32,33). The glomerular and interstitial infiltration by neutrophils increases with the histopathologic severity.…”

T Cells in Crescentic Glomerulonephritis

“…Enhanced IL-10 production by peripheral blood mononuclear cells in patients with IgA nephritis would be consistent with increased Th2 or Treg activity (111). Glomerular T cells and macrophages are more frequent in crescentic forms of IgA nephritis than in noncrescentic disease (112). Both ␣/␤ and ␥/␦ T cells are present in glomeruli of patients with IgA nephritis, and the presence of ␥/␦ T cells correlates with progression of disease (113), although, in children, disease progression has been reported to correlate with the presence of CD8 ϩ T cells (114).…”