Rheumatoid Arthritis - Usual Suspect Genes

By: J.J. Yong

Rheumatoid arthritis (RA) is traditionally considered as a chronic systemic autoimmune disorder of unknown etiology. This disease affects about 1% of the population worldwide, mostly middle-aged women.

It is strongly associated with the inherited tissue type Major histocompatibility complex (MHC) antigen HLA-DR4 which suggests family history is a risk factor.

Characterized by chronic and painful inflammation of the synovium, particularly of small joints, it often leads to destruction of articular cartilage and juxtaarticular bone.

As a systemic disease, it also affects extra-articular tissues like skin, blood vessels and muscles. 60% of the patients are unable to work for 10 years after the condition.

In 2006, researchers at Osaka University Medical School found that if they block an enzyme, DNase II, which is normally used to help break down "waste" DNA (macrophages), that symptoms identical to rheumatoid arthritis occur as that waste DNA accumulates.

Immune system chemical messengers such as TNF-Î? produced, which make the immune system turn on the body and leads to chronic inflammation in the joint, causing arthritis. The genetic defect factor can be overcome by bone marrow transplant.

In 2007, Dr. Peter Gregersen and colleagues at the Feinstein Institute for Medical Research have led the discovery of two suspect genes responsible for increasing the risk for RA.

They are the gene variants, STAT4 that boosts the risk by as much as 60% and TRAF1-C5, which does the same but by a whopping 87%.

Zhen Yan, and colleagues of the Fred Hutchinson Cancer Research Center, pinpointed that circulating fetal cells may account for why rheumatoid arthritis tends to improve or even disappear during pregnancy.

A large proportion of fetal cells in a pregnant woman's bloodstream come from placental cells that have died off as the placenta grows.

The researchers speculated that snippets of human leukocyte antigen (HLA) from the fetal DNA might be picked up by antigen-presenting cells of the mother's immune system, such as dendritic cells.

Lately, a team from Karolinska Institute, Stockholm found a consistent association between the disease and one region of genome on chromosome 9 which includes two genes called TRAF1 and C5.

The chromosome region in which these genes are located may be involved in the binding of a protein that modifies the transcription of genes.

The researchers also found that one of the alternative markers in this region is associated with more aggressive rheumatoid arthritis.

Finally, genetic research and engineering is likely to bring forth many new avenues of earlier diagnosis and accurate treatment in the near future. With the improve knowledge about the susceptible genes to RA, prevention or cure can happen more effectively.

Rheumatology
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