Autoimmune Disease

Having a relative with type-1 diabetes makes you 15 times as likely as other people to get the disease, in which the body inappropriately destroys insulin-producing cells in the pancreas. But unlike the more common form of diabetes, type-2 diabetes, physicians don’t know how to prevent type 1 diabetes from developing in at-risk individuals.

To find out, they’re studying family members of type-1 diabetes patients. The large, multi-center research effort, called Type-1 Diabetes TrialNet, screens these folks for the presence of antibodies that recognize “self” tissues and could act as markers of diabetes vulnerability, and invites individuals who have the autoantibodies to take part in diabetes-prevention research. Stanford and Lucile Packard Children’s Hospital are among the 18 clinical centers participating in TrialNet research.

The big news at TrialNet is that, starting today, the first part of the screening process is moving online. Volunteers used to have to participate in a screening event or come to a trial center to be screened, but many people live far from these centers. At the TrialNet screening website, people can now answer a short set of questions to find out if they’re eligible for TrialNet’s research and give consent to participate in screening. After the online questions are complete, eligible volunteers will receive a kit in the mail that they can take to a local lab for a free screening blood test.

Researchers hope this online process will make it easier for more people to participate in type 1 diabetes research. TrialNet must screen more than 20,000 relatives of people with type 1 diabetes each year to reach its scientific goals, according to an National Institutes of Health press release about the new online screening.

Previously: Beta cell development explored by Stanford researchers, Researchers struggle to explain rise of Type 1 diabetes and A patient perspective on social media

I met Sean Ahrens, a twentysomething patient advocate and founder of Crohnology.com at a recent conference panel on medical blogging. From his presentation and a previous Medicine X video, I knew that he works hard at bringing patients together and spreading the word about a difficult illness. So I wasn’t surprised to hear how active he was during Crohn’s & Colitis Awareness Week, which began Dec. 1.

“We’ve been spending the week honoring the faces - the patients, bloggers, filmmakers, tweeters, songwriters, and community organizers - who are spreading Crohn’s and colitis awareness,” he told me yesterday. “Raising awareness is important because we need to overcome the stigma that there is to live with these conditions.”

A special section of Crohnology has been dedicated to numerous patients’ stories, while another page was designed to honor the work of patient advocates like Ally Bain, a young patient who helped get “Ally’s Law” - which mandates that anyone with a medical emergency be allowed access to an employee restroom - enacted in 12 states; Reid Kimball, a filmmaker who is working on a documentary on people with Crohn’s; and Ken Baumann, an actor who has recently spoken out about his disease.

Their stories are worth hearing.

Previously: Could worms be the answer to treating autoimmune disease? and Living with a chronic disease in college

I’ve read a lot, based on both personal and professional interest, on autoimmune diseases over the years. But I had no idea until this week that the Pacific Northwest has one of the highest rates in the world of one such disorder, multiple sclerosis.

Investigate West and NPR station KUOW are now exploring this issue and have recently posted pieces on the rise in pediatric cases and on the MS research coming out of that region. From one of the articles:

The prevalence is so high here that the Northwest chapter of the National Multiple Sclerosis Society has posted giant billboards around the city for the past several years asking questions like these: Is it the trees? Is it the rain?

The questions may have been rhetorical, but the billboards were a reminder of the need to keep digging for answers about what causes MS.

On a macro scale, scientists actually do know why the rate appears elevated here.

“It’s really the fact we have people here whose genetic background comes from Northern Europe — and that’s the genetic component,” said Dr. George Kraft, director of the Multiple Sclerosis Rehabilitation Research and Training Center at the University of Washington. “And there’s an environmental component. And it may well relate to reduced vitamin D levels. It may relate to other things in this area.”

But what other things? That’s the question [that] researchers are tackling now.

Previously: Stanford neuroimmunologist discusses recent advancements in MS research
Via CoveringHealth

I was presenting on blogging at a medical conference recently when one of my co-panelists, a patient blogger, made reference to the fact that he once explored the use of parasitic worms to treat his Crohn’s Disease. (Boy, did that ever get the audience’s attention!) I was interested, then, to come across a Nature piece (subscription required) on the topic; in it, Tufts University gastroenterologist Joel Weinstock, MD, discusses worms’ effects on the immune system and how infecting certain patients with them might actually help their health. He also shares the epiphany he had one day in the mid-90s, when pondering why “once-rare diseases, caused by autoimmunity” have become relatively common:

I was writing a review article at the time, on inflammatory bowel disease, and editing a book about parasites. That day, I was focusing on a chapter about how the ‘evil’ properties of intestinal parasites are often overblown. Considering the vast number of people who have carried them throughout history, the occurrence of associated disease is surprisingly infrequent. I was reminded of a classic teaching in parasitology, that a ‘good’ parasite imparts some advantage to its host — because if the host dies, so does the worm. Clearly, after thousands of years of co-evolution, the human immune system has evolved to handle the presence of most parasitic worms, which have, in turn, developed adaptations that enable them to live for years in a human host.

Was it possible that improved hygiene, by ridding our bodies of parasitic worms and beneficial bacteria alike, made way for the newer problem of immune-mediated diseases? And could reintroducing parasitic worms protect people against those diseases?

That brainstorm in the middle of a lightning storm has turned into an active area of research. Several ongoing clinical trials, in which patients with inflammatory bowel disease or multiple sclerosis are colonized with an intestinal worm, have produced early evidence that the treatment may be safe and effective.

The rest of the piece is worth reading, though perhaps not over lunch or dinner.

I was 24 years old when I was diagnosed with immune thrombocytopenic purpura, a rare blood disorder that involves the immune system destroying the body’s platelets. It wasn’t an easy diagnosis and only came after several alarming calls from my primary care physician and hematologist, dozens of blood draws, countless cross-country conversations with my nervous parents, and a bone marrow aspiration. Before this experience I didn’t even really know what platelets were, and I certainly wasn’t prepared for the fact that a shortage of them could kill me. In other words: It was pretty scary.

In the decade-plus since my diagnosis, I’ve never met anyone else with this disease - which is why I was so interested in hearing today the (happy) story of YouTube star/ITP patient Reagan Claire Smith. The Atherton, Calif. 10-year-old learned of her ITP at a much younger age than I: She was six when the telltale signs of bruising and petechia brought her to Lucile Packard Children’s Hospital, with platelet counts so low that, as her mom describes, “if she was hit in the head, it could result in bleeding to the brain.” As further explained in a release:

Reagan’s treatment included medicines, hospitalizations and chemotherapy. Nothing fixed the problem. Even a paper cut could send her to the emergency room. “This became a more problematic case, so we decided to do something definitive to help her regain her quality of life,” said [hematologist Bert Glader, MD, PhD], also a professor at the Stanford School of Medicine.

That meant removing Reagan’s spleen, the site of platelet destruction. In 2010, minimally invasive surgery expert Sanjeev Dutta, MD, took it out through her belly button in a no-scar procedure. “Since that time, she’s been in remission and has definitely gotten her life back,” said Glader. Reagan’s platelet counts have returned to normal and her activities are no longer restricted.

Today, Smith (like me) is in good health. And the young girl, who first sang publicly when she was seven and has been in numerous singing competitions since, is taking the Internet by storm; her catchy pop tune “I Wanna Know” is a YouTube and iTunes hit.

I love how her mom puts it: “She was once famous for being sick. Now she’s famous for singing.”

Photo courtesy of the Smith family

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases will share their unique stories; the latest comes from celiac-disease patient and expert Alice Bast.

The day I was diagnosed with celiac disease was the best day of my life.

People always react with surprise when I tell them that. They ask how I can consider being diagnosed with an autoimmune digestive disease such a positive milestone. And I tell them it’s because that’s the day I got my life back.

In hindsight, I believe a vacation to Mexico played a role in triggering the disease. You see, celiac is a genetic condition, so you have to have a genetic susceptibility in order to develop the disease. But there’s something else needed to trigger the onset: an environmental factor, usually some type of emotional or physical stress. There’s little known about it, but in my case, I believe a parasite that I caught on vacation was my trigger. I was treated, but after that, things were never the same.

My husband and I were starting a family, and my oldest daughter was born perfectly healthy after a normal pregnancy. My second pregnancy, though, was nothing like the first. Early on, severe fatigue set in. I was constantly weak and rarely got enough sleep, as severe diarrhea, joint pain and migraines kept me awake at night. No matter what I did, I lost weight. Two weeks before my due date, I lost my baby.

Over the years, I went on to have multiple miscarriages before finally delivering my youngest daughter, who weighed only 2 pounds. For eight years, I visited an incredible amount of doctors - 22, to be exact. No one knew what was wrong with me. At 5’9″, I had wilted to a mere 105 pounds. I thought I was dying. My mother died of pancreatic cancer, and I thought I had cancer too, somewhere - but where? When and how would I find it, and would it be caught in time?

It wasn’t until talking to a family friend, a veterinarian, that I realized that what I was eating could be the problem. She mentioned celiac disease and said that animals can have reactions to wheat. Still on my quest for answers, I visited my 23rd doctor. “Here’s my arm,” I remember saying. ”Give me the blood test.”

Sure enough, the results came back positive for celiac disease. Finally. After eight years of struggling, I had my answer. There’s no cure for celiac, but I was told that by adopting a gluten-free diet and ridding myself of anything derived from wheat, barley, or rye, my health would return and I could live a normal life. And it did. And I did.

But my story doesn’t end with my diagnosis. That’s where it starts.

Continue Reading »

Several years ago, I listened in a state of semi-shock as a doctor gave me a classic bad news-good news combination: The autoimmune system disorder I had was incurable and life-threatening, but researchers had recently discovered that a certain package of medications could put it into remission. I remember that conversation well, but I don’t recall the doctor mentioning much, if anything, about the side effects of those medications.

At age 12, Jena Graves of Napa, Calif. faced the same serious situation. She was diagnosed with the autoimmune system disease lupus, and among her essential medications was the same steroid I was given, prednisone. It’s a go-to medication for millions who suffer from conditions including asthma and diabetes; it’s also on a short list of commonly prescribed “obesogenic” drugs whose effect on the body includes rapid weight gain.

Graves, just 5 feet 2 inches tall, shot up from 120 pounds to 272 pounds and developed Type 2 diabetes and other obesity-related health problems.

A colleague recently shared Graves’ story, which was told again in today’s San Francisco Chronicle. In the piece, Stanford’s John Morton, MD, who performed gastric bypass surgery on Graves this summer, raises a flag on behalf of patients like her:

“All these medications are absolutely wonderful when they work in the right patients,” [said Morton]. “But we’ve got to figure out if it’s appropriate or not to blanket America with prednisone and other obesity-generating drugs that are creating problems.”

Possibly no protein has a worse reputation than beta-amyloid, or A-beta, a protein snippet (or “peptide”) that collects in the brain to become the chief component of clumps called amyloid plaques. Plenty of Alzheimer’s disease researchers believe these plaques are not only a hallmark but in fact a major cause of the condition.

There’s every reason to believe that A-beta is neurotoxic. Yet, in a study just published in Science Translational Medicine, noted multiple-sclerosis expert Larry Steinman, MD, and his colleagues have identified a potentially heroic role for the peptide. When the Stanford investigators injected A-beta into the bellies of mice exposed to a regimen that is known to induce an MS-like condition, A-beta variously reduced, reversed or prevented the paralysis that’s an almost inevitable feature of the mouse version of MS.

When Steinman’s group observed that the experimental mice that got A-beta injections did much better, rather than much worse, than those who’d received blank injections, at first they didn’t believe it.

Many painstaking iterations later, they concluded that A-beta, administered on the far side of the blood-brain barrier, dials down the activity of immune cells that would otherwise invade the mice’s brains and attack the myelin sheathes that insulate many of their nerve cells. In both mice and humans, disruption of these sheathes’ integrity impairs the ability of the long, cable-like nerve cells they surround to transmit signals. This, in turn, can produce a bevy of effects from loss of muscle control to blindness to attention and cognition deficits.

The Alzheimer’s research community is greeting the news with equanimity: “Many substances made in the body can have vastly different functions under different circumstances,” says Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease in San Francisco.

A-beta’s toxicity within the brain has been established beyond reasonable doubt, Mucke says. But A-beta is made throughout our bodies all of the time. Even though it’s been studied for decades, its normal function remains to be identified, he says. “Most intriguing, to me, is this peptide’s potential role in modulating immune activity outside the brain.”

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, Two different types of MS, one big step toward personalized medicine and Stanford neuroimmunologist discusses recent advancements in MS research

The California Institute for Regenerative Medicine today granted cardiothoracic surgeon Robert Robbins, MD, $20 million to lead a team of researchers in an investigation of the use of human embryonic stem cell-derived heart muscle cells in patients with end-stage heart failure, and $20 million to oncologist Judith Shizuru, MD, PhD, to develop an antibody-based method to deplete diseased or dysfunctional blood and immune stem cells in patients with severe combined immunodeficiency. In the video above, cardiologist and co-investigator Joseph Wu, MD, PhD, describes the research proposed in the first grant.

From our release:

“This will be first time anyone has implanted cells derived from human embryonic stem cells into a human heart,” said Robbins, professor and chair of cardiothoracic surgery and director of Stanford’s Cardiovascular Institute. “We’re excited to assess this potential treatment for patients who currently have very few options other than heart transplant.”

Robbins and his colleagues hope to move into human clinical trials within four years, after first testing the transplantation approach extensively in animal models. They plan to enroll about 10 patients in the proposed phase-1 trial.

The two four-year awards were part of CIRM’s second round of disease-team grants. All told, the agency awarded $150 million to eight teams. Stanford investigators received $57.1 million during the first disease-team award round in October 2009.

More from our release about the Shizuru award, which builds on previous work from Stanford’s Irving Weissman, MD:

The Shizuru grant focuses on the use of a monoclonal antibody previously tested in mice by Weissman’s group to remove, or deplete, diseased or dysfunctional blood and immune system stem cells in patients with severe combined immunodeficiency. Currently these cells must be killed by high-dose chemotherapy or radiation, a process that itself can be life-threatening, prior to transplantation with healthy donor cells. Shizuru and her collaborators plan instead to use an antibody that will specifically recognize and eliminate the faulty cells without the use of toxic treatments, enabling patients to more readily accept cells from a healthy donor.

If shown to be effective, the technique could potentially been used to treat many other types of diseases, including sickle-cell anemia and cancers of the blood cells such as leukemias and lymphomas.

A full list of CIRM-funded institutions and descriptions of the disease areas targeted are available on CIRM’s website.

Previously: Stem cell-based heart-attack therapy approved for clinical trials, Lab-made heart cells mimic common cardiac disease in Stanford study and Nature News examines CIRM’s public funding uncertainties

A recent study from the Mayo Clinic showed that obese people are 25 percent more likely than people with a healthy weight to develop rheumatoid arthritis (RA), an autommune disease that causes painful joint inflammation and damage to surrounding tissues. In a Shots blog post today, Gretchen Cuda-Kroen takes a closer look at the findings:

…Although it may seem intuitive that excess body weight could cause joint pain, says Eric Matteson, [MD,] a rheumatologist at the Mayo Clinic who led the study, the link between rheumatoid arthritis and obesity is more than just stress on the joints from being heavy.

“The link, we think, has to do with the activity of the fat cells themselves,” says Matteson.

Unlike osteoarthritis, a form of arthritis that is caused by wear and tear on the joints, rheumatoid arthritis is an autoimmune disease, says Matteson. It occurs when the body’s immune system attacks the lining around joints, and the resulting inflammation leads to the destruction of bone and cartilage. Matteson says it’s the fat cells that stoke the fire of inflammation.

“We have recognized in the past several years that fat cells are important mediators of inflammation,” Matteson says. “They are immunologically active, and they produce proteins that are inflammatory.”

Matteson goes on to say that weight loss may be helpful for patients with RA. Besides helping to relieve joint strain, he says, “losing weight also generally makes the drugs work better.”

Previously: Can yoga help women suffering from rheumatoid arthritis?, A “promising time” for lupus research and Lupus and rheumatoid arthritis may mean fewer children for female patients