3.2.2 Goodpasture's Dz

Question 1

What are the main clinical signs of Goodpasture’s Disease/Syndrome?

Answer 1

Hemoptysis and kidney disfunction

Question 2

What is important about this renal biopsy?

Answer 2

This renal biopsy is showing hypercellularity resulting in circumferential crescent formation

Question 3

What is important about this immunofluorescence microscopy of the kidney?

Answer 3

Linear deposition of IgG antibody characteristic of Goodpasture’s

Question 4

What is important about this direct immunfluorescence of a kidney?

Answer 4

This is IgG staining in linear pattern along the basement membrane.

Question 5

What disease corresponds with these images?

Answer 5

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

Question 6

What is the underlying cause of Goodpasture’s?

Answer 6

Circulating antibodies against an antigen in the glomerular basement membrane

Question 7

What is the allele associated with Goodpasture’s?

Answer 7

HLA-D15

Question 8

What is the target of the auto-antibodies in GP?

Answer 8

Non-collagenous 1 (NC1) domain of the alpha-3 or alpha-5 chain of type IV collagen

Question 9

What is the pathophysiology associated with GP’s?

Answer 9

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.

Question 10

What testing should be done on a person who is suspected of GP’s?

Answer 10

Renal biopsy, Serum assay for anti-GBM antibodies, and ANCAs

Question 11

All four of these images can be correlated to?

Answer 11

Crescent shaped and linear deposition of IgG characteristic of GP’s

Question 12

What is the importance of plasmapheresis in treating GP’s?

Answer 12

It will remove circulating anti-GBM antibodies and also remove complement proteins.

Question 13

What is the idea behind giving high dose steroids when dealing with a patient with GP’s?

Answer 13

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

Question 14

What is the idea behind giving cyclophosphamide to treat GP’s?

Answer 14

It is a strong immunosuppressive agent. Will crosslink DNA, which will affect B cell proliferation and Ig production.

Question 15

What is the idea behind giving Rituximab to patients with GP’s?

Answer 15

It is an anti-CD20 targeting CD20 B cells. This will deplete patients B cells. Make sure to give after plasmapheresis.

Question 16

What is the idea behind giving Azathioprine (Imuran) to patients with GP’s?

Answer 16

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

Question 17

GOOD JOB!