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Arthritis is a common disease, affecting about 1 in 7 of the world's population. It is the leading cause of disability in the USA, and the Centers for Disease Control and Prevention (CDC) in Atlanta predict that more than 60 million Americans will have the disease by the year 2020. The comedian Jack Benny was a sufferer, and famously quipped "I don't deserve this award, but I have arthritis and I don't deserve that either." There are more than 100 types of arthritis, including gout and osteoarthritis, but one of the most serious is rheumatoid arthritis (RA). It affects the joints and can spread to attack several joints in various parts of the body, a condition known as polyarthritis. RA is an autoimmune inflammatory disease in which the body mistakenly attacks its own tissue. Although the cause is unknown, there is considerable evidence that RA is due to oxidative stress and involves excess production of pro-inflammatory compounds. According to the Johns Hopkins University's Division of Rheumatology, RA is found worldwide with a prevalence of 1-2%. It affects women more than men (by up to 3-fold) and is more likely to strike in older people. Those in their 30's to 60's are most susceptible. RA occurs in fluid-containing joints, usually the hands, wrists, shoulders, elbows, knees and ankles. These joints are lined with a thin layer of tissue known as the synovial membrane that protects the cartilage and bone and produces lubricating fluid known as the synovial fluid. The disease thickens the membrane and produces excess synovial fluid, causing the inflammation. In severe cases, permanent and painful deformation of the joints can occur. Currently, there is no cure for RA. Once it sets in, it is irreversible and the main treatments involve controlling the disease and relieving the symptoms. So early diagnosis of RA is especially important. Immunosuppressive drugs are the main form of treatment but recent research has shown that fish oils can reduce morning stiffness and ease painful joints. One of the main problems with early diagnosis is that the symptoms can develop very slowly for quite some time, perhaps over several months, and they can come and go. Usually the first sign is some stiffness in the joints that become tender and painful to varying degrees when moved. More severe symptoms include fatigue, malaise and depression. There are several clinical tests for RA, the most popular being a blood test for a substance known as rheumatoid arthritis factor but most tests give a large proportion of false positive diagnoses. A novel test is now possible thanks to the identification of a new marker of RA that has been found in patients' synovial fluid. In a research study reported in J. Proteome Res. 2002, 1, 495, the proteins in the fluid from RA patients were compared with those for patients with osteoarthritis. The work was carried out in Japan by Takafumi Uchida from the Institute of Development, Aging and Cancer at Tohoku University, with Ai Fukawa and Kenji Saito from Ciphergen Biosystems, Mai Uchida from Hokkaido University in Sapporo and Kyosuke Fujita from Saitama City Hospital. Very small amounts of the liquids (1 ul of diluted fluid) were added to a system known as a protein chip. This is a small array (similar to a DNA array) in which sample wells were coated with special substances to bind the proteins in the fluid. Any unbound components were rinsed away to prevent potential interference with the analysis. By varying the type of absorbent compound, different types of proteins can be retained for comparative studies. After rinsing, an energy-absorbing compound was added to each spot to help with the laser desorption/ionization analysis. Proteins were removed from the surface by the laser, ionized, and analyzed in a time of flight mass spectrometer. The time for a particular protein to travel down the flight tube and reach the detector is related to its molecular mass. This process is known as surface-enhanced laser desorption/ionization (SELDI). By comparing the protein patterns from both types of arthritis, one particular protein was seen exclusively in the RA synovial fluid. It was isolated and its identity was confirmed as migration inhibitory factor-related protein 8 (MRP8), also denoted myeloid-related protein 8 by the authors. This protein appears to be specific to synovial fluid from RA, rather than other forms of arthritis. If its presence is correlated with those of C-reactive protein and rheumatoid arthritis factor, other known markers of RA, then an accurate set of diagnostic compounds for the disease could be established. The research also illustrated the capacity of the protein biochip technology for rapid analysis of proteins without prior chromatographic or electrophoretic separation. The results were obtained in a few hours and could form the basis of a new clinical test for RA. Related links:
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 How rheumatoid arthritis can affect joints |
