Collagen IV, Alport & Goodpasture syndromes

Type IV collagen

• Found notably in basement membranes, basal lamina, and in the lens of the eye.
• Laminin is a major component of basal lamina. Therefore, laminin binds type IV collagen.

Laminin isn’t composed of type IV collagen. It merely is a different protein that binds to it.

Cartilage is type II collagen.

Alveolar and glomerular basement membranes are abundant in type IV collagen. That’s why there’s hemoptysis and hematuria in Goodpasture syndrome.

Alport syndrome

• X-linked (HY on the USMLE)
• Some sources say XR. Others say XD. The USMLE will never make you choose between XR and XD for Alport. But just know that it could theoretically be either.

Codominant inheritance is seen in alpha1-antitrypsin deficiency.

Presents as ear and/or eye problems in a male with red urine (i.e., neurosensory hearing loss, lens disclocations, hematuria)

Alport syndrome = mutations in type IV collagen

Goodpasture syndrome = autoantibodies against type IV collagen

Don’t fuck this up on your exam.

Goodpasture syndrome

• Autoantibodies against type IV collagen (i.e., anti-glomerular basement membrane Abs; anti-GBM Abs)
• More specifically, type-II hypersensitivity due to autoantibodies against the alpha-3 chains of type-IV collagen (2, 3, 4 = type-II hypersensitivity, alpha-3 chains, type-IV collagen).
• A way to remember this is: “2, 3, 4! 2, 3, 4! 2, 3, 4! The Goodpasture is marching in the field. 2, 3, 4!”

Presents as hemoptysis + hematuria generally in a male in his 40s.

The eyes and ears are affected in Alport syndrome.

Hematochezia (frank blood per rectum) is unrelated to either syndrome.

Linear immunofluorescence = super HY + seen in any patient with the disease.

Fibrin crescents are only seen if the condition progresses to rapidly progressive glomerular nephritis (RPGN).

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Linear immunofluorescence on biopsy of the skin, kidney, and lung because of the linear uniformity of basement membranes containing type IV collagen.

• Is a cause of rapidly progressive glomerulonephritis, which will reveal fibrin crescents on renal biopsy under light microscopy.