What are the main clinical signs of Goodpasture's Disease/Syndrome?
Hemoptysis and kidney disfunction
What is important about this renal biopsy?
This renal biopsy is showing hypercellularity resulting in circumferential crescent formation
What is important about this immunofluorescence microscopy of the kidney?
Linear deposition of IgG antibody characteristic of Goodpasture's
What is important about this direct immunfluorescence of a kidney?
This is IgG staining in linear pattern along the basement membrane.
What disease corresponds with these images?
Top - Goodpasture's - Linear deposits of IgG along the GBM
Middle - Lupus Nephritis - Granular deposits of C1q
Bottom - Granulomatosis with polyangitis - Faint deposits of C3
What is the underlying cause of Goodpasture's?
Circulating antibodies against an antigen in the glomerular basement membrane
What is the allele associated with Goodpasture's?
What is the target of the auto-antibodies in GP?
Non-collagenous 1 (NC1) domain of the alpha-3 or alpha-5 chain of type IV collagen
What is the pathophysiology associated with GP's?
IgG antibodies bind to the antigen on the basement membrane. Activation of complement and C3 deposition. Neutrophil dependent inflammation leading to obstruction and glomerular scarring and eventual loss.
What testing should be done on a person who is suspected of GP's?
Renal biopsy, Serum assay for anti-GBM antibodies, and ANCAs
All four of these images can be correlated to?
Crescent shaped and linear deposition of IgG characteristic of GP's
What is the importance of plasmapheresis in treating GP's?
It will remove circulating anti-GBM antibodies and also remove complement proteins.
What is the idea behind giving high dose steroids when dealing with a patient with GP's?
These will bind the intracellular GC receptor which will go to the nucleus and alter transcription of genes. Ultimately it will slow cytokine production and impair T cells
What is the idea behind giving cyclophosphamide to treat GP's?
It is a strong immunosuppressive agent. Will crosslink DNA, which will affect B cell proliferation and Ig production.
What is the idea behind giving Rituximab to patients with GP's?
It is an anti-CD20 targeting CD20 B cells. This will deplete patients B cells. Make sure to give after plasmapheresis.
What is the idea behind giving Azathioprine (Imuran) to patients with GP's?
This is a maintenance therapy after maximum dose of cyclophosphamide has been reached. This is a nucleotide synthesis inhibitor. It inhibits B and T cell function. It inhibits B cell proliferation. Inhibits antibody synth. Inhibits NK cell activity