Raft of Newfound RA Genes May Inspire More Drug Options

Jan 02, 2014

A genome-wide analysis has nearly doubled the count of known genes involved in rheumatoid arthritis, all of them already linked to other conditions. Also new in the nonspecialty journals: Why surveillance goes awry in autoimmune arthritis, and more reason not to fix a torn meniscus.

Last week's articles on rheumatology topics in the major non-rheumatology journals

Nature Letter. Genetics of rheumatoid arthritis contributes to biology and drug discoveryNature, December 25, 2013

The 42 genes newly associated with rheumatoid arthritis (RA) in a genome-wide association study, as widely reported in the public press over the holiday week, bring the total to 101.

These genes are targets of existing drugs for RA, and may lead to the discovery that drugs approved for other indications are also useful for RA.

Two-thirds of the RA risk loci demonstrated pleiotropy with other human phenotypes, including immune-related diseases (for example, vitiligo, primary biliary cirrhosis), inflammation-related or hematological biomarkers (for example, fibrinogen, neutrophil counts), and other complex traits (for example, cardiovascular diseases). There was overlap in somatic mutations for hematological cancers, but not in those for non-hematological malignancies.

Enrichment was found on T-cell-related pathways, B-cell and cytokine signalling such as those for interleukin (IL)-10, interferon, and granulocyte–macrophage colony-stimulating factor (GM-CSF).

 

Also new in the general journals:

Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritisNature Medicine, December 22, 2013

Foxp3+ instability is critical for the generation of pathological T helper (TH17) cells in autoimmunity.

TH17 cells promote inflammation and T regulatory cells (Treg) suppress them. How does this process go awry in autoimmune arthritis?

Under conditions of arthritis, Foxp3+ T cells lose Foxp3+ (which is essential for the regulatory process) to become TH17 cells, and these accumulate in inflamed joints.

These TH17 cells are more aggressively osteoclastogenic than native TH17 cells, which are derived from CD4+ T cells.

 

Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal TearNew England Journal of Medicine, December 26, 2013

Arthroscopic partial meniscectomy was no better than sham surgery for patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear. One hundred and forty-six patients were randomized in a double-blind, sham-controlled trial.

(A previous meniscectoomy trial reported in 2013 compared patients with knee osteoarthritis, and also found no benefit.)

Arthroscopic partial meniscectomy is the most common orthopedic procedure in the U.S. Each year, 700,000 procedures are performed costing $4 billion.

 

Images in Clinical Medicine: Acupuncture with Gold Thread for Osteoarthritis of the KneeNew England Journal of Medicine, December 26, 2013

In Asian countries, acupuncture needles are used to insert small pieces of sterile gold thread around joints, which can appear prominently in radiographs.

A 57-year-old woman with bilateral osteoarthritis of the knees was treated with analgesics, nonsteroidal antiinflammatory drugs, and intraarticular injection of a glucocorticoid, without success. She then tried acupuncture with gold threads.

 

 

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