Systemic lupus erythematosus

Principles to understand

• SLE is an immune complex disease typically with antibodies to dsDNA but to other antigens as well. where does this DNA come from? reticulocytes exude RBC nuclei all the time

• AbAg complexes deposit in blood vessel walls, joints, kidneys (causing arteritis, arthritis, glomerulonephritis)

• the disease waxes and wanes, with varying degrees of severity

• mechanisms of breaking tolerance—read also case 34 (rheumatoid arthritis), noting similarities and differences

Normal clearance of Ab-Ag complexes

• antigen-antibody complexes typically bind to red cells

• the red cells are then carried off to the spleen

• in the spleen, macrophages nip these complexes off the red cells

• when this system is overwhelmed, circulating antigen-antibody complexes can be measured in the blood

• you can imagine that you have to have a lot of such complexes to overwhelm this system

Immune complex disease

• subacute bacterial endocarditis: you make antibodies against Strep., but some of these Strep.-antibody complexes get stuck in glomeruli. these complexes are always a risk for glomerulonephritis

• mixed essential cryoglobulinemia: antibodies against your own antibodies mean that the second antibody can be an antigen. this can happen with hepatitis C and can cause systemic vasculitis

• systemic lupus erythematosus: AbAg complexes cause glomerulonephritis, vasculitis, arthritis

Typical picture of SLE

• butterfly/wolf rash with sun exposure

• also on shoulders, forehead if they were visible

• sun causes a little bit of increased vascular permeability and this causes a little leakage

• in the periphery, this causes antigen-antibody complexes to come out, resulting in a rash

Autoimmunization in SLE

• 
  

  • some B cells floating around have surface receptors for histone H1; when it encounters a piece of DNA with histone bound, it recognizes the antigen

  • the B cell internalizes the receptor-antigen complex and processes the antigen, presenting bits of histone H1 on its MHC

  • then, a histone-H1-specific helper T cell activates the B cell

  • the B cell then starts churning out anti-histone-H1 antibody

• 
  

  • some B cells floating around have surface receptors for DNA; when it encounters a piece of DNA with histone bound, it recognizes the antigen

  • it internalizes the receptor along with the entire antigen and processes it, and by chance, presents some histone H1 peptide on its MHC

  • a histone-H1-specific helper T cell sees this and activates the B cell. the B cell starts making antibodies, and these are anti-DNA antibodies, not anti-histone-H1 antibodies

Category: Pathology Notes