Researchers Find Cause of Rare Immune Disease

Scientists have identified a genetic mutation that causes cold temperatures to trigger allergic reactions—a condition called cold urticaria. Cold urticaria is an allergic disease in which cold temperatures bring itchy, sometimes painful hives, episodes of fainting and potentially life-threatening immune reactions. Earlier research had tied the disease to immune system cells called mast cells. Mast cells release toxic compounds that help destroy invading microbes in a process called degranulation. In people with cold urticaria, mast cells degranulate in response to cold. What leads to this misfire, however, wasn't known. The scientists studied 27 people from 3 separate families. All the participants suffered from an inherited form of cold urticaria. A genetic analysis uncovered mutations in the gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in activating immune cells. These mutations cause the enzyme to function without shutting off. The team named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID.

The researchers found that patients with PLAID can have excessive or deficient immune system reactions. Analysis of blood samples revealed that many participants produced antibodies to their own cells and tissues (autoantibodies), making them more likely to develop autoimmune disease. More than half had a history of recurrent infections. Three had common variable immunodeficiency, which requires frequent intravenous infusions of antibody to prevent severe infections. Seven suffered from granulomas (inflamed masses of tissue) on their fingers, ears, nose and other parts of their skin. Laboratory tests showed that the mutated gene causes abnormal activity in several types of immune cells, including B cells, which are responsible for producing antibodies. Mast cells with the mutations spontaneously degranulate at cool temperatures, which could explain why the patients develop cold-induced hives. These results suggest that inhibiting PLCG2 activity could be a way to treat PLAID. They also suggest that people previously diagnosed with common variable immunodeficiency disease or granulomas might have a PLCG2 gene mutation.

How is hair color determined and why it turns grey?

Genes determine hair color by directing the type and amount of pigment that epidermal melanocytes produce. If these cells produce an abundance of melanin, the hair is dark. If an intermediate quantity of pigment is produced, the hair is blond. If no pigment is produced, the hair appears white. A mixture of pigmented and unpigmented hair is usually gray. Another pigment, trichosiderin, is found only in red hair. The pigment in hair, as well as in the skin, is called melanin. There are two types of melanin: eumelanin, which is dark brown or black, and pheomelanin, which is reddish yellow. Both are made by a type of cell called a melanocyte that resides in the hair bulb and along the bottom of the outer layer of skin, or epidermis. The melanocytes pass this pigment to adjoining epidermal cells called keratinocytes, which produce the protein keratin—hair’s chief component. When the keratinocytes eventually die, they retain the melanin. Thus, the pigment that is visible in the hair and in the skin lies in these dead keratinocyte bodies. Gray hair is simply hair with less melanin, and white hair has no melanin at all. It remains unclear as to how hair loses its pigment. In the early stages of graying, the melanocytes are still present but inactive. Later, they seem to decrease in number. Genes control this lack of deposition of melanin. In some families, many members’ hair turns white in their 20s. Generally speaking, among Caucasians 50 percent are gray by age 50. There is, however, wide variation. Premature gray hair is hereditary, but it has also been associated with smoking and vitamin deficiencies. Early onset of gray hair (from birth to puberty) is often associated with various medical syndromes, including dyslexia.

What are age spots?

Age spots—also known as sunspots, liver spots, or lentigines—are caused by long term exposure to the sun. Age spots are flat, irregular, brown discolorations of the skin that usually occur on the hands,neck, and face of people older than forty. They are not harmful and are not cancerous

Which layers of skin are damaged by burns?

Burns may be caused by heat generated by radioactive, chemical, or electrical agents. Two factors affect burn severity: the depth of the burn and the extent of the burned area. There are three categories of burns: First-degree burns—Burns that are red and painful, but not swollen and blistering, such as from a sunburn, and damage only the epidermis. Second-degree burns—Burns that are red, painful, and blistering, these burns involve injury to the epidermis and the upper region of the dermis. Third-degree burns—Burns that are severely painful, giving the skin a white or charred appearance; they destroy all layers of the skin, including blood vessels and nerve endings. Skin damaged by third-degree burns does not regenerate. Damage to the skin affects the body’s ability to retain fluids.