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Fibrin monomer and its derivatives in blood are found in an early stage of thrombosis. When they are produced in blood, they form complexes with fibrinogen, and they exist as soluble complexes named soluble fibrin (SF). As final insoluble products, cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. To clarify the mechanisms of mesangial SF production and its relationship to XFb deposition in IgA nephropathy (IgAN), an immunohistochemical study was conducted.Nineteen patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure. SF was detected with a monoclonal antibody (IF-43), and factor V was detected with a specific rabbit antibody. The relationships of SF staining to the disease activity index, XFb deposition, and factor V staining was evaluated.XFb, factor V, and SF were observed in the mesangium in 14, 11, and 8, respectively, of a total of 19 specimens. SF had frequent staining in the proliferating areas, showing a significant relationship to XFb or factor V (P0.05). Furthermore, XFb, factor V, and SF depositions were markedly correlated with disease activity (P0.001 in each case).These findings suggest that SF is formed in the mesangial area in active IgA nephropathy accompanied by mesangial proliferation, in particular, in its early stage.