Current uses of ultrasound in rheumatology include differentiating between synovitis or tenosynovitis and gout versus pseudo gout, more easily placing needles for fluid removal with bursae around the knee, helping with a final diagnosis of Achilles enthesis, or showing changes such as thickening of the tendon in subclinical entheseal involvement in psoriasis or other spondylarthropathies.
Pathogenesis of Spondylarthritis
Genetic research has uncovered clues to the pathogenesis of spondylarthritis (SA), said Robert Inman, MD, professor of medicine/immunology at Toronto Western Hospital in Ontario. Specifically, in genome-wide association studies (GWAS), there have been “a number of hits that pop up across the human genome, which is encouraging,” Dr. Inman said.
B27, which has dozens of subtypes, not all of which are associated with SA, is thought to affect disease expression and susceptibility in terms of earlier onset of disease, back pain, and increased inflammation. Research suggests that two additional genes, endoplasmic reticulum aminopeptidase (ERAP) 1 and ERAP-2, seem to be involved.
Dr. Inman and his team used gene silencing to suppress ERAP-1 in B-cell lines and found altered peptide presentation. “If you shut down ERAP, there is an accumulation of intracellular free heavy chains [in the cell] as well as at the cell surface,” Dr. Inman explained. Furthermore, the altered free heavy chain profile on the cell surface is associated with presentation of unusual long peptides, but only in cells expressing subtypes of B27 associated with ankylosing spondylitis (AS).
This is an important area to study at the moment, Dr. Inman said, “because this analysis is beginning to shed light on one of the oldest questions in clinical genetics research: How does HLA-B27 confer susceptibility to AS? Insights into altered peptide presentation that is associated with B27 and ERAP polymorphisms could actually define the molecular basis of AS in particular and immune response in general.”
New Therapeutic Targets in Scleroderma Research
In systemic sclerosis, treatment options focus on symptoms, such as calcium channel blockers or angiotensin-converting enzyme inhibitors for Raynaud’s phenomenon, methotrexate for skin problems, and glucocorticoids plus cyclophosphamide for interstitial lung disease. “We need to get from this current organ targeted approach and get toward a molecular targeted treatment, and to do that we have to understand more how the disease is happening,” according to Sandeep K. Agarwal, MD, PhD, assistant professor of medicine at Baylor College of Medicine in Houston.
A popular pathway that is being studied in scleroderma is the WNT and beta-catenin pathway. The WNT signaling pathway is disregulated in scleroderma patients, and WNT activation in the skin can increase dermal thickness. In an animal model, increasing nuclear beta-catenin leads to an increase in dermal fibrosis. These findings make WNT and beta-catenin “intriguing candidates for therapies down the road,” Dr. Agarwal said.
