Rawle M. McIntosh

Nephropathy associated with sickle cell anemia: An autologous immune complex nephritis: I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis☆

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patients kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

The pathogenesis of the renal lesion in a patient with Streptococcal disease, infected ventriculoatrial shunt, cryoglobulinemia and nephritis

Abstract A case of acute poststreptococcal glomerulonephritis followed by shunt nephritis is presented. The patient manifested both persistent hypocomplementemia and cryoglobulinemia. Investigations into the nature of the glomerular deposits revealed the deposition of a staphylococcal antigen and immunoglobulin G (IgG) and β 1 C globulin in a nodular pattern. No immunopathologic role for the cryoglobulins could be demonstrated, and Streptococcal products could not be identified by immunohistologic methods. The evidence supports a circulating bacterial antigen-antibacterial complex in pathogenesis, and thus the identification of an antigen in human immune complex renal disease.

Cryoglobulins. II. The biological and chemical properties of cryoproteins in acute post-streptococcal glomerulonephritis.

Cryoglobulins isolated from patients with acute post-streptococcal glomerulonephritis, fixed complement in vitro and were associated with inflammatory changes following intradermal administration to unsensitized guinea pigs. Intravenous administration to laboratory animals was followed by clinical and morphologic changes resembling anaphylactic shock or by glomerulitis with the deposition of human IgG but no host IgC on the glomerular basement membrane and in the mesangium. Gel filtration using Sephadex G200 of cryoglobulin solution dissolved in, and eluted with, barbital buffer yielded a single component in the macroglobulin fraction. Gel filtration chromatography using dilute acid yielded 2 components; a large molecular weight component which was not identified by chemical or immunologic methods and another fraction which had the same chemical composition as normal human IgG except for a lower sialic acid content. Streptococcal antibody was not detected in either fraction and streptococcal antigens were not localized in the glomeruli of animals that developed glomerulitis. These studies show that mixed cryoglobulins isolated from patients with acute post-streptococcal glomerulonephritis exhibit properties similar to those of antigen-antibody complexes and suggest that they may have a primary or secondary role in the production of glomerular injury.

Secretory IgA in Urinary Tract Infections

Secretory IgA, measured by radial immunodiffusion, was compared in the urine of children with chronic and recurrent non-obstructive urinary tract infections with that in normal children. IgA, IgG, and IgM were also measured. Absent and low levels of IgA(s) were found in both groups; however, the mean levels of IgA(s) were significantly higher in the infected group compared with normals—3·3 to 0·78 mg./24 hours, respectively. Secretory IgA was found to be locally produced in the bladder. It is suggested that IgA(s) levels reflect an antibody response to infection.

Factor VIII and renal disease.

Excerpt To the editor: Recent studies (1-3) have indicated that levels of factor VIII are increased in chronic renal disease. One study (3) in which patients were seen over a period of 4 years show...

Nephrotic syndrome associated with Fanconi Syndrome. Immunopathogenic studies of tubulointerstitial nephritis with autologous immune-complex glomerulonephritis.

The nature of renal lesions in a patient with simultaneous onset of the Fanconi syndrome and nephrotic syndrome was investigated by immunologic studies of the patients serum, cryoproteins, and renal tissue. Acute severe tubulointerstitial nephritis and generalized segmental glomerulonephritis were present. Renal tubular epithelial (RTE) antigen, IgG, and Clq were localized in the glomerull and proximal tubules. Cryoprecipitates containing RTE antigen and anti-RTE antigen were isolated from the patients serum antibody to RTE antigen was detected in the serum of the patient. However, antibody to tubular basement membrane was not found in the cryoproteins or serum. The unusual simultaneous presentation of these two syndromes in our patient possibly represents a common etiology: tubular damage with release of RTE antigen and subsequent development of immune-complex glomerulonephritis mediated by renal tubular epithelial antigen and antibody to this antigen.

Characterization of the Glomerular Antibody in Acute Poststreptococcal Glomerulonephritis

Glomerular-fixed antibody was eluted from the kidney of a 17-year-old patient who died 2 weeks after the onset of acute poststreptococcal glomerulonephritis. Elevated titers of antibodies to streptococcal enzymes were found in the serum but not in the glomerular eluate. Streptococcal M protein and anti-M protein reactivity were not detected in the eluate. Immunoglobulin G was the only serum protein demonstrated in the eluate, and it was found to have anti-IgG activity highly concentrated with respect to the serum. These studies appear to indicate that anti-IgG is involved in the immune pathogenesis of acute poststreptococcal glomerulonephritis. Native IgG may be rendered autoimmunogenic by the streptococcus with subsequent antibody production to the neoautoimmunogen. Alernatively, anti-IgG may be produced to the IgG incorporated in an exogenous streptococcal antigen-antibody complex.

Anaphylactoid Purpura, Cold Exposure, and Cryofibrinogenemia

Excerpt To the editor: Anaphylactoid pupura (Henoch-Schonlein purpura) is a syndrome of nonthrombocytopenic purpura, arthralgia, abdominal pain, gastrointestinal bleeding, and nephropathy. The caus...

Experimental Pulmonary Disease and Autoimmune Nephritis in the Rabbit Produced by Homologous and Heterologous Choroid Plexus (Experimental Goodpasture's Syndrome)

Summary The choroid plexus basement membrane bears striking immunologic, structural, chemical and functional similarities to glomerular basement membrane and has been suggested to play a role in anti-glomerular basement membrane nephritis. In these investigations serial injections of homologous and heterologous choroid plexus basement membrane in Freunds adjuvant to rabbits was associated with nephritis, hemorrhagic pneumonitis and linear deposits on the choroid plexus and to a lesser extent alveolar basement membrane in rabbits. Proteinuria, hematuria and serum anti-GBM antibodies were prominent. Epistaxis was occasionally present. The nephritis was characterized by linear deposition of host IgG and B1C on the glomerular capillary walls and glomerular eluates contained anti-GBM anti-choroid plexus, alveolar and renal tubular basement membrane antibody. Nephritis was transferred by serum. The studies suggest a role for the choroid plexus in Goodpastures syndrome.

The Nephrotic Syndrome: Current Concepts

Abstract The nephrotic syndrome, an entity of multiple causes, is characterized by edema, proteinuria, hypercholesterolemia, and hypoalbuminemia. It occurs in the child or adult with primary renal ...