Relapses and Their Causes

Posted by Elaine Moore Apr 6, 2007

Autoimmune diseases are characterized by alternating periods of remission and relapses. In relapses patients are free of symptoms and the disease remains inactive. Often, relapses are caused by stress and other known environmental triggers. However, the exact immune mechanisms behind the development of relapses has remained elusive. A possible clue to the process in relapse centers around the high levels of the protein osteopontin, which have been found in brain cells of patients with multiple sclerosis (MS) shortly before they experience relapses.

Osteopontin also appears to be play a role in the disease process in type 1 diabetes, rheumatoid arthritis, and Graves’ disease as well as the malignancies human papillary cancer, melanoma, mesothelioma, colorectal cancer, lung cancer, and ovarian cancer. In addition, osteopontin is increased in the kidney diseases glomerulonephritis and tubulointerstitial nephritis and it is found in the plaques lining the arteries in atherosclerosis. Currently, levels of osteopontin are being studied for their use as markers of disease activity, for instance, in patients with autoimmune disease and various cancers.

What is Osteopontin?

Osteopontin, which is also known as sialoprotein I, is a glycoprotein molecule first discovered in bone in 1986. Osteopontin is produced by various tissues including the immune system’s white blood cells and the cells that make up bone, brain, kidney, placental tissue, and the inner ear. Osteopontin produced by immune system cells is classified as an immune system chemical known as a cytokine or chemokine. Cytokines modulate the immune response.

Osteopontin has been implicated in a number of physiological and pathological events, including maintenance or reconfiguration of tissue integrity during various inflammatory processes including those involved in autoimmune disease development. Osteopontin is expressed by various cytokines including interleukin-1 and tumor necrosis factor-alpha, and its expression is essential for macrophage activity. Of interest, osteopontin has both pro-inflammatory and anti-inflammatory properties depending on which step in the inflammatory process it’s involved in.

Osteopontin in Autoimmune Disease

In experimental studies, mice with experimental encephalomyelitis (similar to MS in humans) given osteopontin experienced flare-ups of disease activity, often in different parts of the nervous system indicating disease progression. Normally, the programmed cell death known as apoptosis regulates the demise of autoreactive cells. Osteopontin, however, appears to interfere with the mechanisms of apoptosis allowing autoreactive immune system cells to perpetuate.

Treatments aimed at blocking the production and activity of osteopontin may prove effective for people with autoimmune disorders. However, because the many properties of osteopontin are still being studied, blocking or inhibiting it may have undesirable side effects. For now, osteopontin is a topic of major concern in controlling autoimmune disease and in the future it may play a key role in treatment.

Resources:

David T. Denhardt, Masaki Noda, Anthony W. O’Regan, Dubravko Pavlin, and Jeffrey S. Berman, Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival, J Clin Invest, May 2001, Volume 107, Number 9, 1055-1061.

Molecule linked to autoimmune disease relapses identified at Stanford, Medical News Today, Dec 6, 2006.

Osteopontin, Wikipedia, accessed March 1, 2007.