Turning now to a disease that is not an organ
specific disease like type I diabetes or the
thyroid autoimmune diseases, but is a
rheumatological condition - rheumatoid arthritis.
In rheumatoid arthritis, there is advanced
symmetrical involvement of joints of the hands.
The proximal interphalangeal and metacarpophalangeal
joints are typically affected in rheumatoid arthritis.
And as you can see on the right hand side, there’s
a radiograph of the hand of a patient with advanced
rheumatoid arthritis illustrating cartilage loss and
bone erosion; very typical of rheumatoid arthritis.
Like all autoimmune conditions, the disease develops because
of the inheritance of a number of susceptibility genes.
HLA being one but several
others have been implicated.
A failure of immunological tolerance and up-regulated
lymphocyte activation of autoantigen specific lymphocytes.
Environmental factors include
infection and smoking.
One of the specific things about rheumatoid
arthritis is that there is a particular
enzyme modification that is occurring,
that is referred to as citrullination.
And this modification of an amino
acid in the sequence of a variety
of proteins leads to the development
of autoantibodies, and T and
B-cell responses to self antigens
within the joint of the patient
with rheumatoid arthritis leads to the development of pathology.
Within the joint, Th17 cells, Th1
cells and plasma cells producing
autoantibodies will cause damage to the synovial membranes.
There are rheumatoid factor autoantibodies which
are autoantibodies against the Fc part of IgG.
So this is an autoantibody
against another antibody.
And these rheumatoid factors can be either
IgM or IgA or IgG rheumatoid factors.
But they all recognize
exactly the same antigen.
That antigen is actually the
Fc part of an IgG molecule.
Little bit hard to get your
head around that, I know.
But just think about it; an antibody is a
glycoprotein molecule just like anything else.
It can act as an antigen.
And in this case the Fc part of IgG is the
antigen being recognized by autoantibodes.
And there are also autoantibodies present
to citrullinated proteins and peptides.
The result is synoviocyte activation,
the production of cytokines and
inflammation, causing the destruction of
both cartilage and the underlying bone.