The research reported today describes a new receptor protein for BAFF, called BAFF-R, and the consequences when mice lack either BAFF or BAFF-R. It demonstrates that both BAFF and BAFF-R are essential for normal B cell development and that mice that lack BAFF and mice that possess an abnormal form of BAFF-R have significantly reduced numbers of mature B lymphocytes. As a result, their ability to generate antibody responses to foreign proteins is compromised. In contrast, mice lacking either of the BAFF receptors previously identified - BCMA and TACI - have largely normal numbers of B lymphocytes and normal or near normal antibody responses. The research thus identifies BAFF-R as the protein through which BAFF primarily acts. Based on these results, BAFF-R is likely to be an especially attractive receptor protein to target in drug development and treatment for diseases such as SLE that involve B cell abnormalities.

"This is a patient who had bloody, watery diarrhea about 10 times a day for nine years, with a lot of abdominal pain. Since the procedure, she has had no diarrhea, is eating and is in no pain,'' Burt said of the first patient.

``But we have to be very careful. This is experimental, one patient never means anything. We can't say we've cured anybody. Only time will tell. But this is obviously the best thing we could have wished for,'' he added.

Multiple sclerosis patients who underwent a similar procedure at another hospital to rebuild their immune systems with their own stem cells showed progress, Burt said. Though the therapy did not repair existing damage to their nervous systems, it halted the development of new lesions, he said.

However, stem cell therapy on lupus patients elsewhere did repair the damage to their organs, Burt said.

Robert Craig, a gastroenterologist at Northwestern working with Burt on Crohn's disease, said it took him three years to find suitable patients for this experimental therapy.

``They need to be very sick. They have to have failed on other therapies. There aren't that many people who are ill enough to warrant this type of therapy because the therapy itself is life threatening,'' he said.

The process is risky because it involves destroying the patient's defective immune system with chemotherapy and a protein that drives down the number of infection-fighting white blood cells.

A growth factor is introduced to stimulate the bone marrow to produce stem cells, which are then harvested from the bloodstream. Finally, the stem cells are injected into a central vein, either in the neck or arm.

The whole process, including recovery, takes three weeks.

``It scares me,'' Craig said. ``I sweat bullets with these patients. When their white blood count is that low they're very susceptible to infection.''

Burt, the chief of Northwestern Hospital's division of Immune Therapy and Autoimmune Diseases, began studying the process of regenerating the immune systems of animal test subjects more than a decade ago.

For instance, scientists have manipulated blood stem cells from adult mice to grow into tissue and that bone marrow stem cells can be made to regenerate heart muscle.

Whether the process will work on human beings is not known, he said.

``Can we use blood stem cells for tissue genesis to repair organs? If we can get a person's adult stem cells to do that from their blood then this whole problem of embryonic stem cells in terms of the ethical problem is not an issue,'' he said.

Autoimmune diseases occur when the immune system attacks the body, instead of foreign organisms or material, as it is designed to do. For example, in rheumatoid arthritis, the immune system attacks parts of the joints, while in multiple sclerosis it attacks parts of the nervous system. Scientists believe that genes and infection with certain viruses may play a role in such diseases.

The researchers studied death certificates from an 11-year period, including more than 143,000 people who had been elementary and secondary school teachers and over 717,000 people in other professions. The team examined how many of these death certificates listed any of 13 autoimmune diseases as a cause of death. Among teachers, 2.3% of the death certificates reported autoimmune disease as a main cause of death, compared with only 1.7% of those in other professions.

The investigators found that overall, schoolteachers had higher rates of death from autoimmune diseases, even when researchers accounted for other factors, such as age, race, or socioeconomic status. Although many autoimmune diseases are more common in women, male schoolteachers were also more likely to suffer an autoimmune disease, the authors note in the Journal of Rheumatology.

Walsh suggested that teachers may be at higher risk of these diseases because they are more likely to be exposed to organisms such as the Epstein-Barr virus, which causes mononucleosis and may be related to autoimmune diseases. There is no way to tell, however, who might be more vulnerable to such disorders.

``This receptor (G2A) and its binding molecule (LPC) open a new and important perspective on the pathology of autoimmune diseases and atherosclerosis,'' they said in a statement.

``Future studies may lead to the development of drugs which mimic or inhibit effects of receptor binding of this molecule in the immune system. Such a drug may prove useful in the treatment of these diseases,'' they explained.

The research was carried out in cell lines in the lab, so the next step will be animal studies designed to see whether the same interactions occur, Xu told Reuters Health.

Even though much about autoimmune diseases remains a mystery, the findings ``underscore the growing realization that the immune system does not operate independently of the tissues that it defends,'' according to Monica J. Carson of The Scripps Research Institute and David Lo of Digital Gene Technologies Inc., both in La Jolla, California.

Blocking TACI prevented the T immune cells from responding normally to an inflammation-promoting chemical called IL-2, the authors report in the July issue of Nature Immunology.

As a result, mice treated with the TACI-blocker showed much less arthritis than untreated mice, the report indicates.

Close examination under the microscope confirmed that the TACI-blocking treatment had minimized the damage to the tissues surrounding the joints. In fact, x-rays of joints from treated mice could not be distinguished from those of normal mice without arthritis, Grewal and colleagues report.

Further experiments confirmed the beneficial effects of TACI blockade on other immune cells (so-called B cells), the researchers found.

Grewal's team concludes that interactions with the TACI receptor ``are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these (interactions) might have therapeutic benefits for autoimmune diseases, such as rheumatoid arthritis, that involve both B and T cells.''

In a related commentary, Drs. Richard Siegel and Michael Lenardo from the National Institute of Allergy and Infectious Diseases (news - web sites) in Bethesda, Maryland express some concern, though, over the potent effects of TACI-blockers. They note that the degree of immunosuppression caused by blocking the TACI receptors is greater than that seen with drugs currently used to treat rheumatoid arthritis.

BLyS (for B lymphocyte stimulator), produced by a variety of immune cells, stimulates the growth of cells that give rise to disease-fighting antibodies. In lupus and similar immune-based diseases, these antibodies turn against the body's own tissues, according to Dr. William Stohl of the University of Southern California (USC) in Los Angeles and colleagues from Human Genome Sciences in Rockville, Maryland.

The researchers wondered whether the levels of BLyS were higher in patients with immune-based rheumatic diseases, so they tested 95 patients with lupus, 67 patients with rheumatoid arthritis and 23 with various other rheumatic diseases. Rheumatic diseases are characterized by joint inflammation and pain.

The investigators found that patients with rheumatic diseases had higher average levels of BLyS than did healthy individuals. Their findings are published in the June issue of Arthritis & Rheumatism.

In seven patients with swollen joints, BLyS levels in the affected joints were even higher than blood levels of BLyS, the authors note, suggesting that BLyS is actively produced in inflamed joints.

These results also suggest that BLyS plays a role in the development of lupus, rheumatoid arthritis, and similar diseases--and that high levels of BLyS might identify patients at higher risk of disease flare-ups, Stohl told Reuters Health.

A blocker of BLyS actions--known as a BLyS antagonist--has shown some positive effects in mouse models of lupus, according to Stohl's team.