SNP Shot: Genomic Insights

PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is an immune disorder characterized by cold-induced allergic reactions and other immune problems. A key sign of PLAID is cold urticaria, which causes a red, itchy rash (hives) when skin is exposed to cold. These hives typically appear due to evaporative cooling, like from a cool breeze on damp skin or air conditioning. Cold swimming pools can also trigger hives. Notably, touching cold objects like ice cubes usually doesn't cause a reaction in people with PLAID, unlike those with other types of cold urticaria. However, some individuals may experience a burning sensation in their throat from cold foods like ice cream. The hives associated with PLAID generally disappear as the skin warms up. Prolonged cold exposure can result in loss of consciousness or a severe allergic reaction called anaphylaxis.

Besides cold urticaria, other skin issues can arise in PLAID. Some affected individuals develop a blistering rash on the nose, ears, and fingers shortly after birth. This rash typically resolves on its own during infancy, but in rare cases, it may worsen. After the initial rash clears, a different rash, known as a granuloma, might appear on the torso and limbs later in life. These granulomas can be localized or widespread, but they typically avoid warm areas like the armpits and skin folds.

Many individuals with PLAID have a weakened immune system, leading to recurrent infections such as frequent colds, ear infections, or pneumonia. These infections are likely linked to lower levels of antibodies or immunoglobulins, particularly IgM or IgG. Antibodies normally attach to foreign particles and germs, marking them for destruction. Furthermore, the number of natural killer (NK) cells, another type of immune cell, may be reduced.

Autoimmune disorders, where the immune system mistakenly attacks the body's own tissues and organs, are also common in PLAID. These disorders can include autoimmune thyroiditis, which damages the thyroid gland, and vitiligo, which causes patchy loss of skin color due to attacks on pigment cells. Most people with PLAID have autoantibodies in their blood, such as antinuclear antibody (ANA). These autoantibodies can bind to normal proteins and trigger an immune response against the body's own tissues. However, the presence of autoantibodies doesn't always mean a person will develop an autoimmune disease.

Inheritance:

PLAID is inherited in an autosomal dominant pattern. This means that only one copy of the altered gene is needed in each cell to cause the disorder. In most instances, an affected individual has one parent who also has the condition.