New Research Builds on Top 10 Research Advances from the Past

Over the years, the Arthritis Foundation has compiled an annual “Top 10” list of research advances for that particular year. Often, Arthritis Foundation-supported researchers are at the helm of these cutting edge advances. These top research advances have given us a glimpse of where research is heading and how care for the person with arthritis will improve with each new discovery. Last year was no exception (see Top 10 Advances).

However, because research builds on itself, we decided to take a look back at a couple of the Arthritis Foundation’s Top Research Advances from a few years ago and to see what is currently being done in those advances.

Protein Marker for RA?

Then
“Protein found to be marker of RA years before symptoms appear.” Similar to the PSA test for prostate cancer screening, research in 2003 provided hope that a routine blood test could screen for rheumatoid arthritis (RA). Compared with healthy individuals, blood samples from people with RA were found to have a significantly higher level of antibodies called “anti-CCP” up to nine years prior to the onset of RA symptoms (Source: Arthritis & Rheumatism, October 2003).

Now
In the latest study, in which Arthritis Foundation-funded researchers, including Lindsay Criswell, MD, of University of California, San Francisco, took part, researchers attempted to further understand the genetics of people with RA and how genetic factors interplay with anti-CCPs. The researchers compared the HLA profiles of people without RA and of those with RA who either did or did not produce anti-CCPs. Included in the study were samples from patients enrolled in the North American RA Consortium (NARAC), led by Peter Gregersen, MD, of the Center for Genomics and Human Genetics in Manhasset, N.Y.

Research performed over the past few decades has studied human leukocyte antigen (HLA) types, which let the immune system know what is “self” and what is an outside invader. As research advanced, the region of the HLA named HLA-DRB1 was shown to have the greatest effect on the genetic risk of RA. Continued research to refine RA genetic risk showed that the HLA-DRB1 alleles encode a shared epitope (SE) – the part of the antigen to which autoantibodies, such as rheumatoid factor (RF), respond.

In the study published in Arthritis & Rheumatism (November 2005), 408 RA patients were examined and tested, with results compared to 423 healthy controls. The study aimed to determine whether the SE and anti-CCPs were associated for sure, whether the SE and anti-CCPs were associated differently in people with RA and in controls, and whether the SE and anti-CCPs were associated with remission or joint destruction.

Results showed that the presence of the SE was not associated with disease in “a substantial proportion of RA patients,” but it was strongly correlated with anti-CCPs. In all analyses, people with RA who tested positive for anti-CCPs, and who had two copies of the SE, had odds ratios that were twice as high as those having just one copy of SE.

By further clarifying factors that characterize RA, doctors may soon be able to use the presence of anti-CCP antibodies to diagnose RA earlier than they do now, and researchers can further narrow the search for mechanisms that cause RA.

MRI Use in OA Evaluation?

Then
“MRI allows earlier detection of OA and prevention of painful symptoms.” In 2003, researchers showed the reliability of magnetic resonance imaging (MRI) in assessing change in cartilage volume over time in patients with knee osteoarthritis (OA) as well as the feasibility of developing standardized measures of cartilage volume (Sources: Osteoarthritis Cartilage, May 2003; Arthritis & Rheumatism, October 2003). In addition, researchers found that changes in the bone underlying cartilage in people with knee OA, especially in those with knee malalignment, predicted who is at risk for disease progression (Source: Annals of Internal Medicine, September 2003).

Now
Researchers continue to examine the use of MRI to assess cartilage of the knee, further demonstrating that examining the cartilage at a molecular level allows physicians to more precisely assess and/or predict the progression of disease. In a recent study published in Arthritis & Rheumatism (November 2005), researchers – including Arthritis Foundation-funded researchers Leena Sharma, MD, of the  Feinberg School of Medicine, Northwestern University, in Chicago, and Deborah Burstein, PhD, of Beth Israel Deaconess Medical Center and Harvard Medical School, in Boston – used delayed gadolinium-enhanced MRI of cartilage (dGEMRIC),  to examine the “health” of cartilage compared with results found when only using X-rays in patients with knee malalignment, which is a risk factor for progression of OA. While conventional X-ray results showed that the amount or “quantity” of cartilage in the knee was unchanged, dGEMRIC revealed that the “quality” or molecular makeup of the cartilage was not as healthy. This study has built on the studies of previous years and shown how the use of MRI in the assessment of cartilage could be used in the clinical setting. While larger, long-term studies are needed to confirm these findings, they show the potential for using MRI to measure tissue health and improve treatment of people with OA.

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