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The Lupus Gene


The Lupus Gene
By A. G. Moore 2/1/2014

Image by BruceBlause
Wikimedia Commons, share alike, attribution license

Headlines about the discovery of a “lupus gene” created a bit of optimism in the lupus community recently. However, as is usually the case, the reality of the breakthrough is more nuanced than the headlines suggest.

Increasingly, research about lupus has focused on the role of B cells in disease activation; for example, the newest lupus drug approved by the US FDA, Benlysta, targets B cells. Although use of Benlysta has proved to be modestly effective, doctors still look to B cells as an area where lupus therapies may be developed. The new “lupus gene”, not coincidentally, is associated with B cell activity.

So what exactly is it that was discovered and why such optimism? It seems that, for years, researchers have recognized the presence of a B cell “receptor”  called Fc. Fc plays a role in antibody suppression. When an infection is detected by the immune system and antibodies are produced, Fc receptors recognize the presence of these antibodies. As the number of antibodies grows and they are no longer needed to fight infection, Fc shuts down production. That’s a good thing. Too many antibodies floating around can end up attacking healthy tissue rather than foreign bodies. So Fc is an ally in the immune response.

However, what scientists at the University of Alabama  claim to have discovered is a variant of Fc, a variant that doesn’t stop antibody production, but stimulates it, leading to over stimulation. Over stimulation is not a good thing. Excess production of antibodies is at the heart of lupus and other autoimmune diseases.

Identifying Fc as a culprit in the chain of events that causes overproduction can be very helpful in understanding and treating autoimmune disease.

Right now, most lupus drugs act by tamping down the immune response; this may curb symptoms but it also generally wreaks havoc on the body. If the variant Fc turns out to be a lupus culprit, as University of Alabama researchers believe, then therapies might be developed that target just this small part of the immune system. To understand the significance of this, think of the fight against lupus as a war. Using Fc-targeted therapies would be like using a sniper to get the enemy rather than using a cluster bomb. It’s obvious that a sniper would cause a lot less collateral damage than a bomb would.

Although headlines may have announced a breakthrough in lupus research, not everyone is in agreement that the “discovery” is indeed valid. Dr. Jeffrey Ravetch, of Rockefeller University, is a key researcher working with Fc receptors. Dr. Ravetch has declared that the University of Alabama’s Fc research is “technically flawed” and doesn’t prove anything. Dr. Ravetch is not likely to be a lone skeptical voice.

Despite the lack of consensus on the variant Fc receptor, it’s important for people who have lupus to understand the ongoing discussion among researchers, no matter how it plays out. Very powerful drugs are prescribed to control lupus–or not, depending on severity of disease. Because lupus drugs are so powerful and taking or not taking them can have profound consequences, patients should understand why the drugs are used and what their use is supposed to achieve. Having at least an idea of what B cells are, what antibody production entails and how this production affects us is part of a discussion we want to be in on. If we’re not in on it, someone else will decide what’s important to us. Whether long-term costs may be exacted for short-term gains, whether the risk of one side effect is more compelling than the risk of another, that’s something we should decide.

An example from my own history illustrates this point: azathioprine was once suggested as a possible therapy to control my lupus symptoms. Azathioprine is a drug that often has good results and may bring about a remission. However, use of this drug also carries a small risk of inducing pancreatitis. This slight risk increases in patients with certain GI conditions. I’ve had pancreatitis and I’ve had serious, recurrent gut issues. My decision, based on my own priorities, was to decline Azathioprine as a treatment option. My doctor had no problem with my decision because it was clear to him that I understood the consequences of my choices.

When it comes to the newly discovered variant of Fc, many more studies need to be conducted before this information can be clinically useful. But a step forward is a step forward. Fc research may be a starting point for more advances.

We can only hope.


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