In a healthy immune system, eff ector and regulator
mechanisms are kept in balance, assuring a tailor-made
response that adequately protects against an invading
pathogen while preventing unwarranted damage to an
individual and preserving immune tolerance. To achieve
this balance, the innate and adaptive immune systems
closely interact. Much the same as with most human
autoimmune diseases, the cause of juvenile idiopathic
arthritis is assumed to be multifactorial. A genetically
susceptible individual might develop a deleterious and
uncontrolled response towards a self-antigen on exposure
to an unknown environmental trigger.32 This response
causes a self-perpetuating loop of activation of both
innate and adaptive immunity that causes tissue damage.
In juvenile idiopathic arthritis, infections and vaccinations
have been suggested as two candidate triggers, but
neither has been confi rmed as a trigger because of a
scarcity of proper controlled, prospective studies.4,32,45 A
prospective study did not show a relation between
vaccination with meningococcus C46 and disease
exacerbation in juvenile idiopathic arthritis, and a
retrospective analysis did not show any association with
measles, mumps, and rubella vaccination and disease
exacerbation.47 Patients with polyarticular disease,
however, showed an increased proinfl ammatory immune
response towards vaccine antigens after vaccination with
meningococcus C, suggesting a potential risk for
aggravating infl ammation.48 Again, much larger studies
including both genetic susceptibility and up-to-date
immunological analysis will be needed to defi ne the role
of environmental triggers in juvenile idiopathic arthritis.