HLA disease associations

There is an established relationship between the inheritance of certain HLA types and
susceptibility to specific diseases. Most commonly these are diseases that are thought
to be autoimmune in nature. Autoimmune diseases are those characterised by
inflammatory reactions that occur as a result of the immune system mistakenly
attacking self tissues. Most autoimmune diseases are characterised by the expression
of class II MHC on cells of the body that do not normally express these proteins. This
may confuse the killer t cells which respond inappropriately by attacking theses cells.
Certain HLA types may look like antigens from foreign organisms . If an individual is
infected by such a foreign virus or bacteria , the immune system mounts a response
against the invader. However there may be a cross reaction with cells displaying the
HLA type that is mistaken for foreign antigen.Whatever the underlying mechanism
certain HLA types are known factors that increase the risk for developing specific
autoimmune diseases.
For example individuals who carry the HLA B-27 allele have a relative risk of 150 for
developing ankylosing spondylitis- meaning such an individual has a 150 fold chance
of developing this form of spinal and pelvic arthritis as compared to someone in the
general population.
Selected association are listed below. Disease name first followed by MHC allele and
then the approximate corresponding relative risk of the disease.
Juvenile diabetes mellitus DR4 6-7
Ankylosing spondylitis B 27 80-150
Multiple Sclerosis DR 2 3
Juvenile diabetes mellitus DR3 5

HLA associated diseases share some general features. Typically the disorders are
chronic, have late onset can often be treated to an extent.
In addition to autoimmune disease, HLA type less commonly plays a role in
susceptibility to other diseases including infections or metabolic diseases. Conversely
some HLA types confer a protective advantage for certain types of infectious diseases.
In addition there are rare immune deficiency diseases that result form inherited
mutations of the genes of components of the MHC.