Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium

Abstract

Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte‐rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte‐rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross‐sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte‐rich areas (P <0.01). Since macrophages and macrophage‐derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.

The Distribution and Abnormal Morphology of Plasma Cells in Rheumatoid Synovium

“…The number of plasma cells in our synovial samples was directly related to the number of infiltrating mononuclear leucocytes and this observation is in accord with the finding that the amount of IgM rheumatoid factor synthesized by synovial cultures correlates with the intensity of T and B cell infiltration [12]. Plastiia cells were not confined to a particular location such as plasma cell-rich areas [ 13], but were present throughout synovial villi and were distributed amongst and below synovial lining cells, in mononuclear cell infiltrates, around small venules and frequently in the blood vessel walls themselves.…”

Increased levels of IgA antibodies to cytokeratin‐18 and epidermal keratin in rheumatoid arthritis

“…It is possible that the increased IgA antibody response to CK-18 in RA patients is a consequence of damage to endothelial cells during inflammatory synovitis. Degenerating endothelial cells and cell debris have been observed in the thickened basement membrane region of postcapillary venules and capillaries in transitional areas of RA synovium containing macrophages, lymphocytes, and plasma cells (21). A number of alternative explanations are possible, however.…”

Effects of UVC Radiation on the Thickness of Glomerular Basement Membrane in Mole Rats

“…The endothelial cells in glomerulus and podocytes are responsible for the production of this membrane (Abrahamson, 1985). Thickening of vascular BM has been studied by a lot of researchers into aging and into a variety of diseases, such as diabetes mellitus, rheumatoid arthritis and polymyositis (Carlson et al, 2003;Matsubara et al, 1987;Tyagi et al, 2008). But, no study has been carried out with regard to demonstrating the effects of UVC radiation on the thickness of GBM in mole rats.…”

“…Adv., 10 (10): 584-591, 2015 A lot of researchers were interested in the thickening of vascular basal membrane in many pathological diseases and a large number of studies have been carried out. But, these studies were mostly related with aging and variety of diseases, such as diabetes mellitus and rheumatoid arthritis (Carlson et al, 2003;Matsubara et al, 1987;Tyagi et al, 2008).…”