Aetiology

·      autoimmune disease

·      aetiology unknown

·      thought to be combination of

·      external trigger (maybe infective agent)

·      genetic susceptibility

autoimmunity
Definition

·      body produces antibodies against is own immunoglobulins

·      antibodies called antiglobulins

·      directed against Fc region of IgG

Process

General

·      exogenous trigger produces antigen

·      antigen somehow alters IgG to become antigenic

·      helper T cells activate B cells to become plasma cells

·      plasma cells produce immunoglobulins (RFs) directed against IgG

·      T cells and B cells chronically antigenically challenged

·      unknown why RF continues to be produced

Specific

·      in RA, synovium acts as lymphoid organ

·      local helper T cells activated

·      local plasma cells produce RF

·      antibody-antiglobulin complexes formed

·      immune complexes stimulate complement

·      inflammatory response occurs

Rheumatoid factor

·      are antiglobulins produced in RA

·      RFs are heterogenous

·       may be IgM, IgG, gA or IgE

·      present in 80% of patients with RA

·      may also be present in

·      infectious and autoimmune diseases

·      hyperglobulinaemias

·      B-cell lymphoproliferative disorders

·      elderly patients

·      RF secreted by plasma cells in synovium

·      high titre RFs associated with more severe disease

·      role of RF in pathogenesis unclear

Measurement

·      classically use agglutination methods

·      most sensitive for IgM

·      usually measured with latex aggregation test

·      latex particles coated with human IgG

·      particles visibly aggregate in presence of RF

·      titre is highest dilution of serum that causes agglutination

·      titre > 1:80 considered positive

Cellular immunity

·      no obvious abnormalities in RA

·      may be deficiency in T suppressor cells

infective agent

·      infectious agent could operate via one of four mechanisms

1.   agent or derived antigens within joint space causes immune response

·      eg. rubella

2.   agent or derived antigens at distant site but immune response causes arthritis

·      eg. Reiter’s syndrome

3.   multiplication of agent in joint space

·      eg. pyogenic infection

4.   agent produces arthitogenic toxins

·      no example known

·      no definite organism or vector found yet

susceptibility

·      associations found with histocompatibility antigens

·      patients with RA have increased incidence of HLA DRW4

·      may reflect genetic susceptibility to develop autoimmune disease