What are the main clinical signs of Goodpasture's Disease?
Kidney Dysfunction and Hemoptysis (Coughing up blood..Lung issue)
What is this called?
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.
What is important about immunofluorescence microscopy of the kidney?
Shows linear deposition of IgG in anti-GBM antibody diease, thus Goodpastures
What is this?
This is the kidney with direct IF. IgG is visualize and a linera staining is found along the GBM. This is Goodpastures
What disease corresponds with these images?
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
What are two main organs affected in Goodpastures?
Kidney and the Lungs
also can see system effects causing weakness and elevated inflammatory markers
What is underlying cause of Goodpastures?
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
-development of antibodies may precede clinical illness by several months
What is genetic association of Goodpastures?
-increase with injury like smoking, viral infection, exposure to gasoline
What is the specific target of the auto-ab in Goodpastures?
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
What is the specific auto-ab type in Goodpastures
typicall IgG subclass 1 and subclass 3
1% of circulating IgG antibodies, rarely IgM or IgA
What is the pathophysiology associated with Goodpastures?
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.
What regulates autoimmune processes?
What type of hypersensitivity is Goodpastures?
Type II b/c antigen is to the NC1 termainl domain of collagen type IV
What organism is MAC important for?
What is a predictor of renal failure in autoimmune disease?
Level of MAC, would find compoenent of MAC in the glomeruli
What would you a Goodpastures CXR show?
Show diffuse infiltrates which are pulmonary infiltrates and associated 30-40% of patients with goodpastures
What testing should be done to dx Goodpastures?
Renal Biopsy, Serum assay for anti-GBM antibodies, and ANCA
What are the treatments for Goodpastures?
-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