The Hunt For Cures: Autoimmune Diseases

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A healthy immune system is the body's best ally--an automated engine of biological warfare that can destroy almost any microbial parasite it encounters. But, like all other agents of destruction, when it spirals out of control, it is as deadly to friend as it is to foe.

Fifteen million Americans know this in their bones. They are victims of a group of more than 40 disorders that arise when the immune system launches a sustained attack against the body. Ailments as diverse as psoriasis, multiple sclerosis and Type I diabetes are all caused by an immune system run amuck. No one knows what initiates any of these chronic diseases or how they might be cured, but researchers have lately made significant headway in developing drugs to treat them--drugs that arguably represent the first substantial advancement in the field in 50 years.

Most of these drugs are genetically engineered biological molecules, and the majority are designed to treat rheumatoid arthritis and its close clinical relative, lupus. Like many other autoimmune diseases, both disorders strike women disproportionately. In RA, the immune system attacks the joints and eventually weakens the bones, causing excruciating pain, fatigue and daily bouts of fever. With lupus, the attack is far more generalized, affecting blood vessels, joints, skin and several internal organs. In severe cases, it can be lethal.

Both can be treated, but there is a catch: the treatments are nearly as harsh as the diseases. Steroids, for example--a mainstay of lupus therapy--shut down the immune system and suppress inflammation, but they can also promote hardening of the arteries, bone loss, obesity and even psychosis. Steroids are, in fact, among the leading causes of death and morbidity for patients with chronic lupus.

But things are looking up, thanks to advances in immunology that have spurred the creation of a new generation of drugs. It is becoming clear that a cell called CD4, or helper T cell, is a key player in both healthy and autoimmune responses. "T-cell activation--like the branches of government--is controlled by a series of checks and balances," explains Dr. C. Garrison Fathman, a clinical immunologist at Stanford University.

One of those checks is the T cell's dependence on another cellular player: the antigen-presenting cell. The APC is an omnivorous creature whose job, among other things, is to gobble up microbial invaders. To initiate the immune response, the APC coughs up a molecule from the bug it has eaten, latches on to a helper T cell and "presents" it with a target molecule, instructing the T cell to prepare its troops for war. This activation is tightly controlled; it cannot occur without the lockstep interaction of several proteins on both cells--one of which is known as CD4.

Once activated, the T cell becomes a sort of commander in chief of immunity, activating the B cell--which secretes antibodies--and prompting the release of a farrago of inflammatory molecular signals.

Autoimmune responses follow a similar course, but the cells targeted belong to the body. "Biological-response modifiers," as the new drugs are known, tamp down that response by blocking communication between the immune system's soldiers.