Biology of Disease

Both insulin dependent diabetes mellitus Type 1 and Addison’s disease are
discussed extensively in Chapter 7. The former is caused by an autoimmune
destruction of the insulin-producing cells in the pancreas; the latter by
autoimmune damage to the adrenal cortex. Both diseases are fatal unless
treated by replacing the missing hormones.

Antiglomerular Basement Membrane Disease

Antiglomerular basement membrane diseases are characterized by
autoantibodies to the glomerular basement membrane (antiGBM). They
include Goodpasture’s syndrome and Goodpasture’s disease. The former
disorder shows glomerulonephritis, pulmonary hemorrhage and the presence
of circulating antibodies to glomerular basement membrane; the latter is
similar, but without the lung involvement. Both diseases are now included
under the more general heading of antiGBM disease. Tissue damage is caused
by antiGBM antibodies binding to the glomerular basement membrane and
activating complement. Complement-mediated inflammation then ensues.
The symptoms of glomerulonephritis include proteinuria and hematuria and
erythrocyte casts (Margin Note 5.3) are seen.

The binding of antibodies to alveolar membranes causes hemoptysis, that is,
the coughing up of blood from the lungs and about 40% of patients experience
chest pain. Hemorrhaging from the lungs may eventually lead to respiratory
failure. There is some suggestion that the binding of antibodies to the alveolar
basement membranes is facilitated by exposure to organic solvents, which
increase the permeability of the alveolar capillaries. The incidence of antiGBM
disease is rare, of the order of 0.5 cases per million in the UK. Unlike most

AUTOIMMUNE DISORDERS

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY &&(

Figure 5.4 Immunofluorescence in autoimmune

thyroiditis. (A) Schematic showing the basis

of indirect immunofluorescence staining of

thyroid antigens by a patient’s serum; (B)

Photomicrograph showing thyroid microsomal

antigens stained with a patient’s serum by

indirect immunofluorescence. Courtesy of

EUROIMMUN AG, Germany.

SS SS

SS

SS SS

SS

SS SS

SS

SS SS SS

Patient's

autoreactive

IgG

A)

Thyroid antigen

Fluorochrome

conjugated

antiIgG

antibody

Thyroid epithelial

cell stained for

microsomal

antigens

B)

Unregulated

production

of thyroid

hormone

Regulated

production

of thyroid

hormone

Thyroid cell

Negative feedback TSH

receptor

TSH

TSH

Normal Graves' disease

Anterior

pituitary

gland Autoantibody

S SS

SSS

SSSSSS

Figure 5.5 Schematic showing how the binding

of an autoantibody to the TSH receptor leads

to Graves disease (right-hand side). The left-

hand side shows how the production of thyroid

hormone is normally regulated by a feedback

mechanism.