Back to Rheumatology Articles
Monday 16th January, 2006
|
|
|
|
New insight into the autoimmune triggers for rheumatoid arthritis among
smokers with shared epitope genes.
|
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Rheumatoid arthritis (RA) is one of the most common
systemic autoimmune diseases, and one of the least
understood. Smoking is the major known environmental risk
factor for RA, though little is known about the mechanisms
involved. HLA-DR shared epitope (SE) genes are a widely
recognized genetic risk factor for RA, though little is
known about how these genes affect autoimmune reactions that
lead to chronic inflammation and progressive joint and organ
damage.
To better understand the interactions between smoking and HLA-DR
SE genes in RA, a team of researchers in Sweden focused on the
disease's distinctive autoimmune hallmark: citrulline, an amino acid
not normally present in protein. While extremely rare in healthy
individuals and relatively rare in other inflammatory conditions,
citrulline-modified proteins are common in about two-thirds of RA
patients and may be an underlying factor in the development of the
disease. To investigate whether smoking and SE genes trigger immune
reactions to citrullinated proteins, the team conducted a
case-control study involving patients with recent-onset RA. The
results, featured in the January 2006 issue of Arthritis &
Rheumatism, suggest that smokers with SE genes are more susceptible
to anticitrulline antibody-positive RA.
The study's 930 early RA patients, drawn from the Epidemiological
Investigation of Rheumatoid Arthritis Study Group, ranged in age
from 18 to 70 years. 383 healthy controls, drawn from the blood bank
of northern Sweden, were matched for age, gender, and residential
area. All participants completed questionnaires about their past and
present smoking habits, as well as genotyping profiles. In addition,
bronchial fluid was obtained from a representative sample of RA
patients, including both current heavy smokers and lifelong
non-smokers, and tested with immunostaining for the presence of
citrullinated protein in cells.
Based on their series of experiments and comparisons, the
researchers found that a history of smoking increases the risk for
RA, but only for individuals who test positive for anticitrulline
antibodies, regardless of the presence of SE genes. Similarly,
inheriting HLA-DR SE genes in a single copy, as well as in double
copies, increases the risk for RA, but only for individuals who test
positive for anticitrulline antibodies, including individuals who
have never smoked. Yet, for individuals who test positive for
anticitrulline antibodies, the interaction of smoking and carrying 2
copies of the SE gene dramatically increases the risk for developing
RA--by 21 times.
"The remarkable gene-environment interaction observed in the
case-control study, together with the immunostaining for
citrullinated proteins, might now provide a clue to the molecular
mechanisms of importance for disease development in a subset of RA
patients," notes team spokesperson Dr. Lars Klareskog of Karolinska
Institutet, Stockholm. "We may thereby be given some new
opportunities to both predict and understand the onset of RA and to
interfere with RA-inducing events before clinical symptoms are
apparent."
|
|
printer
friendly version
