3/21/2023

Joint Tissue Findings Offer Potential Insight into Rheumatoid Arthritis

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 people with arthritis is actually offering investigators a better understanding of the antibodies involved in rheumatoid arthritis (RA), a condition in which longterm 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 very own healthy tissues.

The NIH Explains that Two Autoantibodies

Rheumatoid factor as well as anti-cyclic citrullinated peptide (anti-CCP) - circulating in the blood of many individuals with RA have been useful for diagnosing RA and also predicting it's severity, but researchers have little understanding of what these autoantibodies actually do in the joint, or even 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., as well as Diane Mathis, Ph.D., and their colleagues conducted complex checks of joint tissue samples taken from 18 patients with RA. While their investigation did not necessarily find a "third antibody," the researchers did discover 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 connect with Dna in the formation of chromosomes. The histone debris may be derived from cells that died and spilled their contents, which result from the disease problem. 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 hardly ever removed in the course of surgery, the scientists compared their findings to those from samples from eight patients with osteoarthritis (OA, a type of arthritis not generally associated with autoantibodies). The differences 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't say whether histones sitting down on the cartilage surface are presenting in order to antihistone antibodies and contributing to inflammation, but that is a possibility, says Doctor. Monach.

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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 delivers potentially damaging enzymes to the cartilage surface. Dr. Monach believes that following up on these and other hypotheses may eventually lead to the development of pharmaceuticals that would intervene in or prevent the process, as well as thereby slow down combined swelling and damage in RA.

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    These results 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 researchers to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, contact the info Clearinghouse (877) 22-NIAMS or look at the NIAMS Web site at http://www.niams.nih.gov.

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