Damping Down Diabetes

PrevalenceSRxA’s Word on Health was very excited to learn of some amazing new research coming out of UC San Francisco.  Scientists there have identified a new way to manipulate the immune system and keep it from attacking the body’s own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis.

More than 100 different autoimmune diseases have been discovered and they disproportionately affect women.  Of the 50 million Americans living and coping with autoimmune disease  more than 75% are women.  Autoimmune diseases are one of the top 10 leading causes of death of women under the age of 65 and are responsible for more than $100 billion in direct health care costs annually.   Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis and scleroderma by themselves account for > $50 billion.

eTACBut now, researchers, led by immunologist Mark Anderson, MD, PhD, a professor with the UCSF Diabetes Center, have discovered a type of immune cell called an extrathymic Aire-expressing cell (eTAC), which puts a damper on immune responses.  eTAC’s are a type of  dendritic cell – which make up less than 3% of the cells in the immune system. And, eTAC cells themselves account for a small fraction of all dendritic cells. eTACs reside in lymph nodes and spleen in both humans and mice.

In this study, Anderson’s team determined that eTAC’s can counteract the overactive immune response in autoimmune diseases and, in a mouse model of diabetes, can be manipulated to stop the destruction of the pancreas.

By displaying “self” molecules to T cells that target them, and permanently turning off these T cells, eTACs help the immune system tolerate the molecules naturally present within us.  “The mouse model we are working with involves using T cells that normally attack the islet cells of the pancreas, specifically by recognizing a molecule called chromagranin A that is present on islet cells,” Anderson said. “But if the eTACs can get to the T cells first and display chromagranin A, they can prevent T cells from attacking the islets.”

mouse diabetesAnderson aims to exploit eTACs therapeutically by finding out how to grow them in large numbers outside the body. “We need to figure out how to grow a lot of these cells, to load them up with whatever molecule it is that we want to induce tolerance to, and then to load them back into a patient,” he said. “Such a strategy could help selectively shut down an unwanted immune response, such as the anti-islet immune response in type 1 diabetes.”

Dendritic cells work with T cells a bit like a sheriff working with a bloodhound.  But instead of presenting an article of clothing, dendritic cells present a specific molecule. If the molecule displayed by the dendritic cell matches the one the T cell was born to target, then that T cell would be activated to expand its numbers and to attack cells or tissues where the molecule is present.

When the interaction is between eTACs and T cells, however, the targeted T cell instead is turned off forever, and never seeks its molecular prey.

Diabetes wordcloudGiven that the prevalence and incidence of and type 1 diabetes and other autoimmune diseases, such as Crohn’s, lupus and celiac disease are on the rise, this new research is extremely important, both from a public health and economic perspective.  With as many as three million Americans having type one diabetes and the incidence growing by more than 3% per year a cure is desperately needed.

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What’s Your Skin Saying?

Aside from being the largest organ in our body, our skin protects us against invasive bacteria, regulates our body temperature, and picks up information from the stimulation of touch, pressure, pain, heat, and cold. Little wonder, then, that when there’s something wrong with your health that your skin is often the first to know.

Here’s the skinny on several dermatologic oddities worth watching out for:

Orange palms and soles

What it means: The cartoonish skin hues can be the unfunny result of an underactive thyroid gland. Hypothyroidism causes increased levels of beta-carotene in the blood. When there’s a thyroid problem, the gland doesn’t metabolize the vitamins as quickly, so beta-carotene accumulates. Orange skin can also occur due beta-carotene as a result of a diet heavy in carrots, carrot juice, sweet potatoes, and squash.

More clues: The skin of someone with hypothyroidism also tends to be dry and cold, and sometimes more pale than yellowed. Feeling tired, sluggish, weak, or achy are the main symptoms, along with possible unexplained weight gain. Women over 50 most often develop hypothyroidism.

What to do: Carotenemia caused by a skewed diet isn’t serious and resolves itself when a broader range of foods is consumed. Hypothyroidism, however, is a medical condition that can lead to complications such as heart problems, and warrants attention from a doctor.

Breaking out in hives in the sun

What it means: Being truly allergic to the sun is pretty rare. A more likely explanation is having taken a photosensitizing drug that increases the person’s sensitivity to light. One of the most common culprits is thiazide diuretics prescribed for hypertension. Other meds that can produce this effect include antihistamines, tetracycline, and tricyclic antidepressants.

More clues: The rash is limited to sun-exposed areas, including the forearms, the neck, and, less commonly, the face. It can feel worse and last longer than a sunburn.

What to do: Check the labels of your prescription medications. Look for phrases such as “May cause chemical photosensitivity.”

Long dark lines in the palm

What it means: A palm-reading mystic might have her own interpretation, but to a physician, a deepening of the pigment in the creases of the palms or soles is a symptom of adrenal insufficiency – Addison’s disease.

More clues: Hyperpigmentation may also be visible around other skin folds, scars, lips, and pressure points

What to do: It’s important to see a doctor, as skin changes may be the first symptoms seen before an acute attack. Lab tests to measure cortisol will provide a diagnosis.

Large, dusky blue leg veins

What it means: If you’ve got ropy, blue-to-purple lines snaking up your legs this could be a sign that some of your veins are not working properly.

More clues: Varicose veins are sometimes mistaken for spider veins, a weblike network of smaller blue or red veins closer to the skin’s surface. Varicose veins tend to be larger, darker, and sometimes raised, with a twisted appearance.

What to do: Exercise, compression stockings, and avoiding constricting postures (like crossing your legs when seated) can help ease discomfort, but they won’t make varicose veins disappear. While not all faulty veins cause problems, severe venous insufficiency can lead to blood clots and need to be treated.

Brownish spots on the shins

What it means: The fronts of the legs tend to bang and bump into things a lot. For someone with diabetes, the damage to the capillaries and small blood vessels that are characteristic of the disease will cause them to leak when traumatized, leading to brown discoloration known as diabetic dermopathy.

More clues: The brownish patches may also be rough, almost scaly and tend to form ovals or circles.

What to do: There’s no health danger from diabetic dermopathy, and no need for treatment.

Persistent rash that you want to scratch raw

What it means: Clusters of small, ferociously itchy blisters that show up repeatedly in the forearms near the elbows, the knees, the buttocks, the back, or the face or scalp are a hallmark of celiac disease, or an allergy to gluten.

More clues: The rash appears on both sides of the body. Itching and burning are so intense you can hardly quit scratching.

What to do: Report the rashes to your doctor or a dermatologist to evaluate and rule out other causes. A gluten-free diet for life is usually advised to keep symptoms at bay.

Purple stains or splotches

What it means: What looks a bit like a bruise, is often mistaken for a bruise, but tends to hang around longer because it’s not exactly a bruise, may be purpura.   It has several possible causes, ranging from a bleeding disorder (thrombocytopenia) to vitamin C deficiency to excessive intake of aspirin, NSAIDs, vitamin E, ginkgo biloba, coumadin, or alcohol.

More clues: A classic bruise tends to turn black and blue following an injury. With purpura, there doesn’t need to be any trauma, the discoloration persists longer than a bruise and the purple color doesn’t blanch when you press it. Purpura are most common on the forearms, legs, and backs of the hands.

What to do: Report the condition to your doctor who can help to identify the cause and recommend the appropriate treatment.

Intense itchiness without rash

What it means: Feeling itchy can have many causes, but when there’s no accompanying visible skin change, it may be  one of the first symptoms of Hodgkin’s disease or non-Hodgkin’s lymphoma.

More clues: The itchiness is more intense than that caused by ordinary dry skin. It occurs most commonly, in the lower legs. Less often, the skin looks reddish and inflamed.

What to do: Report persistent, intense itching to your doctor.