02 January 2007
Findings published online today in the prestigious Journal of Experimental Medicine may offer new hope to people suffering from a previously unsuspected form of lupus.
Professor Fabienne Mackay, Director of the Autoimmunity Research Unit at the Garvan Institute of Medical Research, has come to believe that a proportion of lupus patients may have a type of lupus that does not correlate with current knowledge about the disease, and therefore may not always be prescribed the best treatment.
“Current thinking about lupus tells us that it is a disease driven in great part by a co-operation between the two types of cells that normally help us fight infection or cancer, B cells and T cells,” explained Professor Mackay. “A proportion of patients are not responding to treatments aimed at disarming B and T cell collaboration, which suggests that additional mechanisms driving lupus may exist.”
“Some lupus patients (22-25%) have surprisingly high levels of BAFF (B cell activating factor, a molecule normally needed for B cell survival and maturation) in the blood. While this research is in its early stages, we believe these findings may relate to patients’ unresponsiveness to some treatments.”
Professor Mackay’s lab has previously shown that elevated levels of BAFF triggers lupus and Sjögren’s disease in mice, and has subsequently questioned the role of this factor on the T/B cell collaboration thought to drive lupus.
“Laboratory tests have shown that mice with high levels of BAFF, but without the capacity to develop T cells, can develop an autoimmune disease that is indistinguishable from the disease requiring collaboration of both types of cells. This finding was very surprising and has entirely changed the way we look at mechanisms driving lupus, especially the notion T/ B cell collaboration in the genesis of the disease, which we now realise may not apply to all situations.”
“While our findings may sound academic, they will radically impact clinical thinking about the development of autoimmune diseases, where the body attacks itself, in particular lupus and Sjögren’s disease.”
“Advances in research knowledge change clinical thinking and so bring about changes in patient management and in clinical trial protocols. If scientists can prove that patients with high levels of BAFF have a B cell-specific disease, doctors can give specific treatments to target the rogue B cells. Instead of prescribing immunosuppressants, such as Mycophenylate mofetil, and seeing no improvement, they can prescribe B cell specific drugs, such as Rituximab – a B cell depleting agent.”
Professor Mackay’s new results have also identified subsets of B cells with pathogenic roles. Using sophisticated gene profiling techniques, her lab has identified molecules expressed on the rogue B cells but not normal cells. This will allow the design of new treatments specifically targeting rogue B cells while sparing useful normal B cells, in contrast to currently available B cell therapies, which do not discriminate.
Notes to editors
Joanna R. Groom,1 Carrie A. Fletcher,1 Stacey N. Walters,2 Shane T. Grey,2 Sally V. Watt,3 Mathew J. Sweet,4,5 Mark J. Smyth,3 Charles R. Mackay,2and Fabienne Mackay1 BAFF and MyD88 signals promote a
lupuslike disease independent of T cells