Goodpasture's Disease

Question 1

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

Answer 1

Kidney Dysfunction and Hemoptysis (Coughing up blood..Lung issue)

Question 2

What is this called?

Answer 2

This is a renal biopsy showing hypercellularity resulting in cicumferentrial crescent formation. Fibrin deposition is noted along with compression of capillar lumen. Classic for Goodpastures disease and will decrease kidney function.

Question 3

What is important about immunofluorescence microscopy of the kidney?

Answer 3

Shows linear deposition of IgG in anti-GBM antibody diease, thus Goodpastures

Question 4

What is this?

Answer 4

This is the kidney with direct IF. IgG is visualize and a linera staining is found along the GBM. This is Goodpastures

Question 5

What disease corresponds with these images?

Answer 5

Top is Goodpastures with linear deposits of IgG along the GBM

Middle is Lupus Nephritis with granular deposits of C1q

Bottom is granulomatosis with polyangittis with faint deposits of C3

Question 6

What are two main organs affected in Goodpastures?

Answer 6

Kidney and the Lungs

also can see system effects causing weakness and elevated inflammatory markers

Question 7

What is underlying cause of Goodpastures?

Answer 7

Circulating antibodies against an antigen in the glo9merular basement membrane.

• both a B and T cell process
• Ab production is for a short time (so pt can randomly get better)
• acute, rapidly progressive
• cresenct formation
• development of antibodies may precede clinical illness by several months

Question 8

What is genetic association of Goodpastures?

Answer 8

HLA-D15

-increase with injury like smoking, viral infection, exposure to gasoline

Question 9

What is the specific target of the auto-ab in Goodpastures?

Answer 9

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

-this is foundin BM of alveoli and glomeruli

Question 10

What is the specific auto-ab type in Goodpastures

Answer 10

typicall IgG subclass 1 and subclass 3

1% of circulating IgG antibodies, rarely IgM or IgA

Question 11

What is the pathophysiology associated with Goodpastures?

Answer 11

IgG antibody bind to the antigen of the basement membrane. Activation of compement and C3 deposition. Neutrophil dependent inflammation leading to obstruction and glomerular scarring and eventual loss.

Question 12

What regulates autoimmune processes?

Answer 12

Tregs (CD25+)

Question 13

What type of hypersensitivity is Goodpastures?

Answer 13

Type II b/c antigen is to the NC1 termainl domain of collagen type IV

Question 14

What organism is MAC important for?

Answer 14

Nisseria

Question 15

What is a predictor of renal failure in autoimmune disease?

Answer 15

Level of MAC, would find compoenent of MAC in the glomeruli

Question 16

What would you a Goodpastures CXR show?

Answer 16

Show diffuse infiltrates which are pulmonary infiltrates and associated 30-40% of patients with goodpastures

Question 17

What testing should be done to dx Goodpastures?

Answer 17

Renal Biopsy, Serum assay for anti-GBM antibodies, and ANCA

Question 18

What are the treatments for Goodpastures?

Answer 18

• Plasmapheresis to remove circulating anti-GBM antibodies, and all other ab’s
• high dose steroids tapered off over 6 months
• steroid sparing agents like cyclophosphamide (immunosuppressive, crosslinks DNA inducing cell death), targets B cells, lookout for hemorrhagic cystitis
• Rituximab (anti-CD20), give after plasmapheresis