What type of collagen is targeted in Goodpasture syndrome?

Type IV Collagen is the Target in Goodpasture Syndrome

In Goodpasture syndrome, type IV collagen, specifically the alpha-3 chain of type IV collagen (α3(IV)), is the target antigen. 1, 2, 3

Pathophysiology of Goodpasture Syndrome

Goodpasture syndrome (also called anti-GBM disease) is characterized by:

• Autoantibodies directed against the non-collagenous domain (NC1) of the alpha-3 chain of type IV collagen
• Linear deposits of these antibodies along the glomerular basement membrane
• Clinical manifestations of pulmonary hemorrhage and rapidly progressive glomerulonephritis 1

Specific Target Details

The autoantibodies in Goodpasture syndrome target specific regions within the NC1 domain of the α3(IV) collagen chain:

• Two major conformational epitope regions have been identified:

  • Residues 17-31 (referred to as E(A))
  • Residues 127-141 (referred to as E(B)) 2

• These epitopes are normally sequestered within the hexamer configuration of the NC1 domain in healthy tissue and become accessible to antibody binding only when dissociation of the hexamer occurs 2, 4

• The E(A) epitope appears to be immunodominant, accounting for 60-65% of the total immunoreactivity to α3(IV)NC1 2

Diagnostic Approach

The diagnosis of Goodpasture syndrome relies on:

1. Serologic testing for anti-GBM antibodies (may have dual positivity with ANCA in 30% of cases)
2. Kidney biopsy showing:
   • Crescentic glomerulonephritis
   • Linear IgG deposits along the glomerular basement membrane on immunofluorescence 1

Clinical Presentation

Patients with Goodpasture syndrome typically present with:

• Pulmonary hemorrhage that may precede, occur simultaneously with, or follow renal involvement
• Rapidly progressive glomerulonephritis with hematuria, proteinuria, and declining renal function
• Laboratory findings of elevated creatinine, microscopic hematuria with dysmorphic RBCs, and moderate proteinuria (1-3 g/day) 1

Treatment Approach

Immediate therapy for patients with Goodpasture syndrome includes:

• Plasmapheresis (plasma exchange) - particularly important for pulmonary hemorrhage
• High-dose glucocorticoids
• Cyclophosphamide 1

Important Distinctions

Goodpasture syndrome must be distinguished from other causes of pulmonary-renal syndrome, particularly ANCA-associated vasculitis, as treatment approaches may differ. The presence of pulmonary hemorrhage increases mortality risk, making prompt diagnosis and treatment essential 1.

The specificity of autoantibodies for the α3(IV) collagen chain has been unambiguously established through research using recombinant NC1 domains. These antibodies react strongly with the α3(IV) NC1 domain but not with other type IV collagen chains (α1, α2, α4, or α5) 3.

The identification of type IV collagen as the target antigen in Goodpasture syndrome has allowed for the development of specific diagnostic tests and potential therapeutic approaches targeting this autoimmune response 3, 5.