Immune Complex Nephritis Research Articles

Inhibition of antibodies to nuclear antigen and to DNA in New Zealand mice infected with lactate dehydrogenase virus.

New Zealand mice developed antibodies to nuclear antigen leading to immune-complex nephritis. Humoral antibody was directed primarily against denatured DNA, although antibody to native DNA was also found. Persistent infection with lactate dehydrogenase virus significantly lowered antibodies both to nuclear antigen and to DNA in these mice. In addition, female (NZB x W)F(1) mice infected with lactate dehydrogenase virus were protected from the usual nephritic death occurring after the trapping of complexes of nuclear antigen and its antibody and of DNA and its antibody in the glomerular filter.

168.The significance of disseminated intravascular coagulation in the mechanism of immune complex nephritis

168.The significance of disseminated intravascular coagulation in the mechanism of immune complex nephritis

Induction of experimental autologous immune-complex glomerulonephritis by eluted gamma-globulin.

A progressive type of immune-complex glomerulonephritis has been produced in rats by the injection of eluted gamma-globulin from kidneys of donor rats with advanced autologous immune-complex (AIC) nephritis. It is suggested that the temporary proteinuria, induced by a nephrotoxic serum, allowed the eluted gamma-globulin to come in contact with the nephritogenic antigen in the renal tubules. The mechanism which might be responsible for the development of the progressive disease is discussed.

IMMUNE COMPLEX DISEASE IN CHRONIC VIRAL INFECTIONS

Chronic viral infections of animals associated with immune complex disease resemble a number of human disorders. At present, on the basis of showing (a) virus, host antiviral antibody, and C3 deposited in a granular pattern along the glomerular capillary wall and in the mesangia and (b) virus-host Ig (presumably antiviral antibody) complexes in the circulation, immune complex disease occurs in chronic murine infections with LCM, LDV, MSV, and ADM. In addition, granular deposits in the glomeruli in Coxsachie B, polyoma, other leukemic viral infections in mice, equine anemia, and hog cholera suggest that immune complex disease also occurs in these infections. In transplacental LCM infections maternal antiviral antibody transferred in utero or via milk induces very early and severe immune complex disease. The severity of immune complex nephritis in mice neonatally or transplacentally infected with LCM virus is directly proportional to the amount of Ig elutable from the kidney and to the proportion of this Ig which reacts with the infecting virus.

PATHOGENESIS OF IMMUNE COMPLEX GLOMERULONEPHRITIS OF NEW ZEALAND MICE

Observations based on elution of IgG from nephritic kidneys of NZ mice and absorption of the eluted IgG with selected antigens indicate that their immune complex nephritis involves at least two kinds of antigen-antibody complexes. Antibodies reactive with nuclear antigens account for nearly half of the IgG eluted from the kidneys while antibodies reactive with Gross viral antigens make up a significant but lesser amount. Superimposed chronic viral infections affect the nephritis of NZ mice in different ways. LCM and polyoma infections hasten and intensify the antinuclear antibody responses and glomerulonephritis of these mice while LDV infection appears to protect against both antinuclear antibody formation and development of nephritis.

Induction of autologous immune complex nephritis in rats by heterologous anti-kidney mitochondrial antiserum

A disease similar to autologous immune complex nephritis has been produced in rats by heterologous anti-rat kidney mitochondrial antiserum injected intravenously during a phase of mild proteinuria induced by bovine serum albumin (BSA) or nephrotoxic serum. The significance of this finding in relation to induction and progression of this type of nephritis is discussed.

KIDNEY TRANSPLANTATION FOR RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

Two patients oliguric from rapidly progressive glomerulonephritis received successful kidney grafts from cadaver donors. Each had poststreptococcal immune-complex nephritis. They both tolerated periodic hæmodialysis and bilateral nephrectomy well. One patient, despite stable renal function, has had persistent proteinuria since transplantation. Examination of a biopsy specimen, taken 2 years after grafting, showed electron-dense deposits consistent with recurrent immune-complex disease, but no proliferative glomerulonephritis. Patients with renal failure from poststreptococcal rapidly progressive glomerulonephritis can be treated successfully by hæmodialysis and transplantation.

The induction of autologous immune-complex nephritis in neonatally thymectomised rats.

The induction of autologous immune-complex nephritis in neonatally thymectomised rats.

Cryoglobulins. I. Studies on the nature, incidence, and clinical significance of serum cryoproteins in glomerulonephritis.

Abstract Cryoglobulins were isolated from the sera of 14 of 18 patients with acute poststreptococcal glomerulonephritis, 4 of 4 with nonstreptococcal proliferative glomerulonephritis, and 2 of 3 with membranous nephropathy. They were not detected in patients with end-stage renal disease lipoid nephrosis, acute streptococcal pharyngitis, rheumatic fever, and normal persons. Cryoglobulins contained IgG and β 1C , and in 3 patients IgM was also present. Their presence was associated with activity of renal disease. A relationship between persistence and progression and disappearance and improvement was suggested. There was no correlation between the presence or quantity of cryoglobulins and levels of immunoglobulins or complement in the serum. Antistreptococcal or rheumatoid factor activity could not be demonstrated in any of the cryoprecipitates. IgG, β 1C , and occasionally IgM were localized in the renal glomeruli by immunofluorescence. The identification of these same proteins in the cryoglobulins of these patients suggests that cryoprecipitates may be of immunopathologic significance in immune complex nephritis.

Persistence of the Autoimmune Pathogenetic Process in Experimental Autologous Immune Complex Nephritis

Abstract The histopathologic, immunohistochemical and physiologic evidence of chronicity and continued activity of the pathogenetic process in experimental autologous immune complex nephritis has been supported by transplanting normal syngeneic rat kidneys 3 to 18 months after the initial eliciting immunogenic challenge, and observing the subsequent localization of specific pathogenetic antigen-antibody complexes in the glomeruli of these “detector” kidneys. The evidence indicates an active pathogenetic process and continued synthesis of small amounts of antoantibody to RTE-α5 for a prolonged period following primary sensitization.

Experimental autologous immune-complex nephritis: An electron microscope and immunohistochemical study

A correlative ultrastructural and immunohistochemical study of the kidney has been performed in rats with autologous immune-complex nephritis, induced by repeated injections of tubular antigens incorporated in Freund's adjuvant. In the glomeruli, electron-dense deposits located on the epithelial half of the capillary basement membrane were seen. The cytoplasm of the foot processes located close to the intramembranous deposits showed an electron-dense material with similar morphologic features. The basement membrane of the proximal tubes was markedly increased in thickness and presented electron-lucid areas. By means of acid phosphatase-labeled antibodies against rat γ- and β- 1 C globulins it was possible to demonstrate that the glomerular electron-dense deposits and the proximal tube basement membrane contained autologous globulins. On the basis of these observations it was suggested that the immune complexes responsible of the renal damage locate selectively in those parts of the nephron which normally deal with the filtration and resorption of proteins, and that the pedicels of the glomerular epithelial cells are engaged in the removal of the intramembranous deposits.

Autologous Immune Complex Glomerulonephritis

Summary Transfer of lymphoid cells from rats with autologous immune complex nephritis induced by intraperitoneal immunization with renal tubular antigen consistently failed to produce disease in normal rats of the same inbred strain. On the contrary, transfer of isologous lymphoid cells from rats with disease induced by intracutaneous and footpad immunization produced a similar, although clinically mild disease, which appeared only after a latent period equal to that needed for the active induction of disease. These observations and those concerning the nature of parabiotic transfer of this disease are consistent with but do not conclusively prove the concept that active immunization of the cell recipient by transferred antigen may play a role in the transfer phenomenon along with any antibody which may be formed by the transferred cells.

Autologous immune complex nephritis induced with renal tubular antigen. I. Identification and isolation of the pathogenetic antigen.

The nephritogenic antigen, responsible for the immunogenic stimulus in experimental allergic glomerulonephritis induced with tubular antigen, has been identified as a renal tubular epithelial (RTE)-specific antigen and has been isolated in a relatively purified form. This antigen, RTE-alpha(5), is a distinct and antigenically specific lipoprotein of high density which is derived primarily from the brush border of proximal convoluted tubular epthelium of the rat kidney. It has been suggested that this molecule may be a plasma membrane subunit. Immunization of rats with as little as 3 microg N of RTE-alpha(5) in complete Freund's adjuvant has effectively induced this form of membranous glomerulonephritis. RTE-alpha(5) is not a constituent of normal rat glomeruli; however, with the onset of autologous immune complex nephritis it is deposited in a granular fashion along glomerular capillary walls indistinguishable from the deposits of gamma-globulin and complement. The antigenic specificity of this antigen and its tissue derivation has been explored, and the observations support the autologous immune complex pathogenesis of the glomerulonephritis induced in rats by immunization with renal tubular antigen.