Self & Other
10. Autoimmune Disease: Friendly Fire
Maya is sixteen. She is in a hospital bed in a pediatric ICU in a city in the Pacific Northwest. She has been there for two days. She is going to be there for two more.
Her moms are with her. Lisa, who runs a small graphic design studio and who drove Maya to the emergency room on Tuesday night when Maya could not stop being thirsty and could not stop throwing up; and Dani, who teaches high school chemistry, who flew back from a conference in Chicago at four in the morning when Lisa called. It is now Friday. Maya is going to be fine. She is also, in some specific and irreversible ways, going to be different.
The previous month had been strange. Maya had been thirsty in a way she could not explain. She drank water all day and was thirsty again ten minutes later. She got up at night to pee, sometimes three times. She lost weight — not a lot, maybe seven pounds — even though she was eating more, not less. She was tired in a way that did not lift after sleep. Lisa and Dani noticed but did not panic. Teenagers grow strangely. Sleep gets weird. The volleyball season was demanding.
Then, on Tuesday, Maya threw up at lunch. By Tuesday evening she was throwing up every twenty minutes. By the time Lisa got her to the ER her breath had a faint sweet smell, like nail polish remover, and she was breathing too fast and saying things that did not quite make sense. The triage nurse looked at her once and stopped asking questions and started moving.
Maya, it turned out, was in diabetic ketoacidosis. Her blood sugar was over 600 milligrams per deciliter, roughly six times normal. Her body, unable to use the sugar in her blood for fuel, had switched to burning fat, and the byproducts of fat-burning had made her blood acidic enough to threaten her organs. She would be put on IV insulin for the next two days. By Friday she would be talking again, eating again, asking when she could go home, asking what was going to happen now.
The diagnosis the doctors gave her family was Type 1 diabetes. The pancreas, the small organ behind her stomach that produces the hormone insulin, was no longer producing enough of it. There was no infection. There was no injury. There was no obvious external cause. Her own immune system, sometime in the last several months or perhaps the last several years, had identified the insulin-producing cells in her pancreas as foreign, and had killed almost all of them.
This is the chapter this book has been building toward. The chapter where the system we have spent nine chapters describing makes the kind of mistake it makes in millions of people every year, and we have to talk about what that mistake is, why it happens, and what it means for the people who live in the bodies it happens to.
Maya is fictional. She is also, in the broad outlines of her story, every teenager who has ever been diagnosed with Type 1 diabetes — the thirst, the weight loss, the trip to the ER that turned into the rest of her life. There are tens of thousands of Mayas every year, in the United States alone. There are millions more people, of every age and every gender, living with one of the roughly eighty conditions we collectively call autoimmune disease.
This is what is happening, biologically, to all of them. This is the chapter.
What Was Happening Inside Maya
Recall, from Chapter 7, the schools of tolerance.
Every T cell in the body has been through the thymus, where it was tested twice. The first test asked: can you read the body’s MHC molecules at all? The second test asked: do you respond, dangerously, to any of the body’s own proteins? T cells that failed the first test were deleted because they were useless. T cells that failed the second were deleted because they were dangerous. The few that passed both tests were released into circulation, where they would, in theory, recognize foreign things and leave the body alone.
In theory.
We said in Chapter 7 that the system was excellent but not perfect. Some self-reactive T cells slip through. Most of them, throughout most people’s lives, are kept quiet by the regulatory T cells we met then — the Tregs, walking the body’s tissues, telling overreacting cells to stand down.
In Maya, somewhere along the line, a small number of T cells with receptors that recognized a protein on her insulin-producing pancreatic cells — a protein that is part of normal insulin, or part of the cellular machinery that makes insulin, or part of the surface of the cells that produce insulin — escaped both the thymus’s negative selection and the regulatory backup. They became active. They began to find and kill the cells they were tuned to.
These cells are called beta cells, and they live in tiny clusters scattered throughout the pancreas, called islets. There are perhaps a million islets in a healthy adult pancreas, each one containing a few hundred to a few thousand beta cells. The beta cells produce insulin in response to rising blood sugar. The insulin tells the rest of the body to absorb the sugar and use it. Without insulin, the sugar stays in the blood, and the body’s cells, paradoxically, starve.