A 25-year-old with anti-GBM disease (Goodpasture syndrome) has linear IgG along the GBM on immunofluorescence. The target antigen is the NC1 domain of COL4A3 (α3 chain of type IV collagen). This specific chain is absent from which anatomical location, explaining why only glomeruli and lung alveoli are affected?

• A It is absent from Bowman's capsule and renal tubular basement membranes
• B It is absent from skin basement membrane and most vascular basement membranes ✓
• C It is present exclusively in glomeruli and absent in alveoli
• D It is absent from mesangial matrix but present in extraglomerular vessels

Explanation

The α3α4α5 network of type IV collagen is uniquely expressed in glomerular and alveolar basement membranes (and also in some ocular membranes), but is absent from skin, liver, and most vascular basement membranes which express the α1α2 network. This tissue-restricted expression of the α3(IV)NC1 antigen explains the organ specificity of Goodpasture syndrome (lung-kidney involvement). Skin biopsy IF is therefore negative (unlike SLE), which helps differentiate anti-GBM disease.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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