Intraglomerular Deposition of Intact Cross-Linked Fibrin in IgA Nephropathy and Henoch-Schönlein Purpura Nephritis

Abstract

To investigate the significance of intraglomerular coagulation and fíbrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (XL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean ± SD = 1.6 ± 0.9) than in the negative group (n = 6; 0.5 ± 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 ± 1.0) was higher than that in IgA-N (n = 13; 0.9 ± 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially in HSPN.

Factors affecting histological regression of crescentic Henoch–Schönlein nephritis in children

“…Although less extensively studied in humans [22], the beneficial effects of urokinase in Japanese patients with severe HSN also indicate an important functional role for fibrinogen [10,23]. We also showed that the number of glomerular crescents was reduced according to the disappearance of fibrinogen deposition, and post-therapeutic fibrinogen deposition was influenced by the age at onset.…”

Henoch-Schönlein purpura nephritis: an update

“…The coagulation system is possibly involved in the pathogenesis of HSPN as suggested by the ®nding in one study of a circulating factor able to inhibit PGI2 synthesis [83], the depletion of ®brin-stabilising factor (factor XIII) in acute HSP, increased plasma von Willebrand factor levels [20,78], and the intact crosslinked ®brin (XFb) intraglomerular deposits [66]. As already mentioned, glomerular ®brin deposits may be abundant in HSPN.…”

Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis

“…Clinically, crescent formation is observed frequently in human microscopic polyangiitis 29,30 and occasionally in the active type of human MsPGN such as IgA nephropathy and Henoch-Schönlein purpura nephritis. 31 Fibrin is considered to be chemotactic for leukocytes. 32 Where the crescent is formed, fibrin, T cells, macrophages, and tissue factor are consistently observed.…”