Macrophages in childhood IgA nephropathy

Abstract

The role of glomerular macrophages in IgA nephropathy in children was investigated using a new monoclonal antibody (KP1) as a probe. The average number of glomerular macrophages per patient (ANM/P) was closely correlated with the degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P < 0.01) in the absence of any correlation with proteinuria, serum IgA levels or the interval between the detection of urine abnormalities and renal biopsy. ANM/P was significantly higher in patients diagnosed pathologically as having focal and diffuse proliferative glomerulonephritis than in patients with minor glomerular abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular morphology in individual patients, macrophages predominantly infiltrated glomeruli with cell-proliferative lesions despite an absence of any increase in glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly localized within the capillary lumen in association with endocapillary proliferative lesions (tuft necrosis), they accumulated in areas of mesangial proliferation, and they were attached to Bowman's capsule in segmental lesions. Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis revealed macrophages in the paramesangial areas in close proximity to lytic changes in the glomerular basement membrane and effacement of epithelial foot processes. In addition, some cases in repeat biopsy shows prolonged or increased values of ANM/P after several years of interval in association with progression of proliferative lesions. These results suggest that macrophages infiltrate glomeruli during acute glomerular inflammation, and that they are involved in mesangial proliferation or the development of extracapillary lesions in the absence of apparent clinical symptoms. Furthermore, recurrence or prolonged infiltration may promote progression of IgA nephropathy.