Nerve, immune link found on membranes.

Nerve, immune link found on membranes

Certain hyperactive immune system diseases disrupt nerve cells, but the immune-nervous system interaction lacks a molecular explanation. Researchers at the University of California at San Diego (UCSD) now have one candidate link -- proteins that apparently appear on both immune system cells and nerve cells. The proteins, they say, could be at the root of such autoimmune diseases as multiple sclerosis and systemic lupus erythematosus.

To study the surfaces of nerve cells and white blood cells, Ken D. Pischel, Harry G. Bluestein and Virgil L. Woods Jr. of UCSD used antibodies against very late activation antigens (VLAs). These VLAs, recently discovered by Martin Hemler at the Dana Farber Cancer Institute in Boston, appear on white blood cells after the cells become active in fighting infection. The antibodies found and attached themselves to three proteins on nerve cells identical to the three subunits of VLA, the San Diego group reports in the August JOURNAL OF EXPERIMENTAL MEDICINE. Other cell types have been found to have one or two of the subunits, but neuronal cells are the only type shown to have all three, Bluestein says.

While research in other laboratories has shown other shared molecules on nerve and immune cells, the UCSD researchers believe the VLAs are more likely to be involved in the disease process. "This one is of particular interest to people interested in immunologically modulated diseases of the nervous system because it appears with the activation of the lymphocytes [white blood cells]," says Bluestein. His laboratory has preliminary evidence of antibodies to VLA in systemic lupus erythematosus, an inflammatory disorder that can affect a variety of organs.

While the exact connection between VLAs and lupus remains to be defined, Bluestein suggests one possible scenario: In the initial autoimmune disease, antibodies against VLAs on suppressor white blood cells destroy the immune system's "brakes." The same antibodies might also attack VLA-studded nerve cells, causing neurological problems. About 40 percent of people with lupus have neurological problems; half of this group suffers seizures or mental impairment with cognitive dysfunction.

In the spinal fluid of patients with multiple sclerosis, an autoimmune disease that specifically strikes nerve cells, Hemler's laboratory has found white blood cells with unusually high levels of VLA on their surface. Antibodies against the lymphocytes' VLA, Bluestein suggests, could also be attacking the nerve cells.