Joint Tissue Findings Offer Potential Insight into Rheumatoid Arthritis
According to the National Institutes of Health, new research supported in part by the national Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) looking directly at joint tissue in individuals with arthritis is offering investigators a better understanding of the antibodies involved in rheumatoid arthritis (RA), a condition in which persistent inflammation causes pain, stiffness and damage to the joints. Antibodies are molecules that participate in the immune system's protection of the body by recognizing harmful antigens such as viruses and bacteria. In RA, antibodies called autoantibodies are directed against a person's personal healthy cells.
The NIH Explains that Two Autoantibodies
Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) - circulating in the blood of lots of people with RA have been useful for diagnosing RA and also couples its severity, but researchers have little knowledge of what these autoantibodies actually do in the joint, or perhaps whether the joints themselves might have clues to other antibodies contributing to the disease. To find some answers, NIAMS-supported researchers, Paul A. Monach, M.D., and also Diane Mathis, Ph.D., and their colleagues conducted complex tests of joint tissue samples taken from 18 patients with RA.
While their investigation failed to necessarily find a "third antibody," the researchers did find that antibodies that came out of the joints actually bound to a lot of products associated with joint cartilage and also to histones, intracellular proteins from the cell nucleus that associate with Dna in the formation of chromosomes. The histone debris may be derived from cells that died and spilled their items, which be a consequence of the disease situation. Furthermore, they found that cartilage in RA is actually coated with histones, regardless of whether RA was active or not.
Because normal joint tissue is rarely removed during surgery, the scientists compared their findings to those from samples from eight patients with osteoarthritis (OA, a form of arthritis not generally associated with autoantibodies). The distinctions between the OA as well as RA samples were striking; the OA cartilage samples were not covered in histones. Right now, the actual scientists can not say whether histones seated on the cartilage surface are binding to antihistone antibodies and contributing to irritation, but that is a possibility, says Medical professional. Monach.
He says if histones are a contributor to joint damage, there are also other theories about their role. One is that they stimulate immune cells through a class of proteins called Toll-like receptors (TLRs). Another is that they may be key in a process that provides potentially damaging enzymes to the cartilage surface. Medical professional. Monach believes that following up on these and other hypotheses may eventually lead to the development of drugs that would intercede in or prevent the process, and also thereby slow down joint swelling and damage in RA.
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These conclusions were published in the Proceedings of the National Academy of Sciences.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and medical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, phone the info Clearinghouse (877) 22-NIAMS or visit the NIAMS Web site at http://www.niams.nih.gov.
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