Penicillamine associated pulmonary hemorrhage.

Penicillamine is the drug of choice in Wilson's disease and a therapeutic alternative in rheumatoid arthritis. Autoimmune complications associated with penicillamine include cases resembling systemic lupus erythematosus and Goodpasture's syndrome. We report a case of diffuse pulmonary hemorrhage associated with prolonged penicillamine use in a patient with Wilson's disease with evidence of circulating immune complexes and complement activation, but without serologic or morphologic evidence of systemic lupus erythematosus, Goodpasture's syndrome or renal disease.

The pathogenesis of hyaline arteriolosclerosis.

Although hyaline arteriolosclerosis is very common and has been of interest to pathologists for well over 100 years, its pathogenesis has never been determined. This study demonstrates that iC3b bound via an ester linkage to hydroxyl groups on the repeating disaccharide units of hyaluronic acid is a major component of arteriolar hyaline. The deposition of iC3b within the walls of arterioles appears to be due to slow spontaneous activation of the alternative complement pathway and random binding of metastable C3b to proximate hyaluronic acid within the arteriolar wall. Since hyaluronic acid does not activate the alternative complement pathway, bound C3b is rapidly inactivated by factors I and H to iC3b, which, along with factor H, remains bound to hyaluronic acid. The hyaline in some hyalinized arterioles also contains IgM and early and late classical complement pathway components. Indirect evidence suggests that the IgM represents immunoconglutinin, an autoantibody to neoantigens on iC3b and that their interaction results in activation of the classical complement pathway. The gradual accumulation of iC3b, factor H, and, at times, IgM and classical complement pathway components within the walls of arterioles is considered to be a physiologic consequence of aging and probably cannot be prevented, because interruption of the initial binding of metastable C3b to hyaluronic acid would require abrogation of the critically important functions of the alternative complement pathway.

Immune complex glomerulonephritis and dermal vasculitis following intestinal bypass for morbid obesity.

A kidney and skin biopsy were performed on a patient who developed cryoglobulinemia, polyarthritis, a purpuric skin rash, and acute renal failure four years following jejunoileal bypass for morbid obesity. Morphologic studies revealed a diffuse glomerulonephritis characterized by the presence of numerous subendothelial deposits containing IgG, IgA, C3, Clq, C4, and properdin, and an acute dermal vasculitis associated with similar immune complex deposits. Identical immunoglobulin and complement components were present in the cryoglobulin. In addition, both the cryoglobulin and a renal biopsy eluate containing anti-IgG antibody and antibody against Klebsiella pneumoniae which were present in the patient's stool in large numbers. Combined therapy with steroids and chloramphenicol resulted in marked improvement in the patient's arthritis, skin rash, and renal function. The findings indicate that glomerulonephritis and dermal vasculitis due to the deposition of bacterial antigen-antibacterial antibody complexes may occur as part of a systemic immune complex disease complicating small intestinal bypass.

The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Behçet's disease.

A kidney and lung biopsy were performed on a patient with active Behçet's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Behçet's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition.

Immunopathogenesis of Libman-Sacks endocarditis. Assessment by light and immunofluorescent microscopy in two patients.

The possible contribution of immunological mechanisms in the development of Libman-Sacks endocarditis was studied in 2 patients with systemic lupus erythematosus who underwent aortic valve replacement. Sections of verrucous lesions, stained with haematoxylin and eosin, showed three apparently distinct zones: an outer exudative zone of fibrin, nuclear debris, and haematoxylin-stained bodies; a middle organizing zone of proliferating capillaries and fibroblasts; and an inner zone of neovascularization which showed distinct, thin-walled junctional vessels. The striking finding was the apparently selective deposition of immunoglobulins and complement identified by direct immunofluorescence, within the walls of the small junctional vessels of the zone of neovascularization. We suggest that the observed immune deposits are immune complexes and that circulating immune complexes may play a critical role in the growth and proliferation of the verrucous lesion.

Periodic acid-Schiff-light green stain to detect glomerular protein deposits by routine light microscopy.

A simple, easily reproducible periodic acid-Schiff-light green stain (PAS-LG) for the detection of glomerular protein deposits by routine light microscopy is described. The deposits are selectively stained a deep blue and contrast sharply with the staining of adjacent glomerular structures. Correlation with immunofluorescent and electron microscopy has shown that it is possible with this stain to categorize accurately a large variety of glomerular lesions by light microscopy alone.

Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits.

A renal biopsy was performed on a patient with syphilitic glomerulonephritis characterized clinically by the acute onset of nephrosis that responded dramatically to penicillin therapy. Histologic, electron microscopical and immunohistochemical studies revealed an early membranous glomerulonephritis characterized by the presence of subepithelial basement-membrane deposits containing IgG and C3. The glomerular lesion, however, differed from that in the usual case of membranous nephropathy in that distinctive segmental lesions were present at the tubular poles of the glomeruli, and all the glomeruli exhibited mild proliferation of mesangial cells in association with the presence of IgM within mesangial areas. Antibody elution studies performed on the renal-biopsy specimen demonstrated the presence of antitreponemal antibody within the glomerular immune-complex deposits. This finding indicates that the glomerular injury occasionally complicating secondary syphilis is due to the deposition of treponemal antigen-antitreponemal antibody complexes.