The Goodpasture antigen in Alport's syndrome: Studies with a monoclonal antibody

Abstract

A mouse monoclonal antibody (MCA-P1), which recognizes an antigenic determinant in human glomerular basement membrane against which autoantibodies are directed in Goodpasture's syndrome, was used in indirect immunofluorescence studies to investigate glomerular basement membrane structure in Alport's syndrome. We found reduced or absent binding of MCA-P1 to glomerular and distal tubular basement membranes in renal biopsy tissue from ten patients with Alport's syndrome. Antiglomerular basement membrane antibody eluted from the kidneys of a patient who had died from Goodpasture's syndrome was used to confirm these findings. In contrast, there was bright linear fluorescence of MCA-P1 on glomerular and tubular basement membranes of normal renal material and renal biopsy tissue obtained from patients with a variety of glomerulonephritides. These results suggest an abnormality or a variable quantity of the immunoreactive autoantigen in the glomerular basement membrane of patients with Alport's syndrome. Furthermore, MCA-P1 may be of value in the diagnostic interpretation of renal biopsies from patients with familial nephritis.

Alport’s Syndrome: Risk of Glomerulonephritis Induced by Anti-Glomerular-Basement-Membrane Antibody after Renal Transplantation

“…These findings suggest that the absent GBM antigen is related to the nephritogenic antigens(s) of Goodpasture's syndrome. Savage et al [12] have recently confirmed this finding, using a mouse mon oclonal antibody (MCA-PI) which recognizes the Good pasture's antigen. Using an indirect IF technique, they found reduced or absent binding of MCA-PI to glomeru lar and distal TBMs in renal biopsy tissue from 10 pa tients with Alport's syndrome.…”

Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen.

“…It is known that antibodies recognizing the Goodpasture antigen do not bind to the GBM ofmost patients with Alport's syndrome, a hereditary nephritis that is usually transmitted in an X-linked manner (43,44). The existence of the a5 chain of type IV collagen had not been suspected biochemically or immunologically, but its gene is located in the appropriate region of the X chromosome (10), and abnormalities ofthe COL4A5 gene have since been identified in 3 of 18 Alport kindreds (45).…”

Recurrent Allograft Antiglomerular Basement Membrane Glomerulonephritis in a Patient with Alport’s Syndrome

“…Several determina tions of serum anti-GBM antibodies have been negative in all the patients. A possible explanation for this is vari ation in the quantity of immunoreactive auto-antigen in different patients with Alport's syndrome [10]. There may be considerable heterogeneity of inherited nephritis of the Alport type, and/or the degree of binding may reflect sex differences in the amount of antigen present in the basement membrane, since most patients with absent binding of Goodpasture serum were male in Sav age's study [10].…”