Pathogenic role of the IgA molecule in IgA nephropathy

SUMMARY: Deposits of IgA together with complement in different body tissues support the hypothesis that IgA can trigger inflammatory mechanisms. IgA nephropathy (IgAN) is characterized by predominant mesangial IgA₁ deposits of a polymeric nature. So far, the mechanism of polymeric IgA₁ deposition in the kidney mesangium is poorly understood in IgAN. the exact pathophysiological sequel preceding renal fibrosis following the mesangial deposition of IgA immune complexes remains speculative. Recent in vitro studies revealed that binding of IgA to mesangial cells led to increased expression of growth factors, cytokines, and integrins. the release of these proinflammatory factors is likely to enhance inflammatory injury. In addition, the local renin-angiotensin system present in renal tissues also contributes to renal fibrosis through the activation of transforming growth factor-β. the question of whether polymeric IgA isolated from patients with IgAN exerted any upregulatory effect on the synthesis of macrophage migration inhibitory factor (MIF) and components of the renin-angiotensin system in human mesangial cells was explored. the in vitro studies revealed that polymeric IgA from IgAN patients upregulated the gene expression of renin and MIF in human mesangial cells in a dose-dependent manner. These findings further support the notion that glomerular deposition of IgA is not only a pathological epiphenomenon of IgAN, but that polymeric IgA exerts a pathophysiologic effect on the mesangial cells leading to renal fibrosis.     

Ultrastructural observations on beaded α-motoneuron dendrites

Beaded dendrites of 1α-motoneurons intracellularly labelled with horseradish peroxidase (HRP) were studied ultrastructurally in eight adult cats. For comparison, adjacent unlabelled beaded dendrites of unknown origin were also included in the study. Electron microscopy revealed no signs of degeneration or poor fixation according to common criteria. With the exception of the HRP-reaction product no difference in structure was observed between labelled and unlabelled beaded dendrites. Both the beads and their interconnecting segments were postsynaptic to boutons of normal appearance containing spherical (S-type boutons) or flattened vesicles (F-type boutons). The values for synaptic covering and synaptic packing density of the beaded dendritic regions, which usually were located in the periphery of the dendritic trees, were clearly lower than values obtained previously for cell bodies and proximal dendrites of a-motoneurons.