PLCG2-associated antibody deficiency and immune dysregulation

PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is an immune system disorder characterized by an allergic reaction to cold temperatures. Other immune system problems can also occur. The hallmark feature of PLAID is the development of a red, itchy rash (hives) when the skin is exposed to cool temperatures, which is known as cold urticaria. In PLAID, the hives typically develop in response to evaporative cooling, such as when a cool breeze or air conditioning blows on damp or sweaty skin. Being in a cold swimming pool can also trigger hives. In contrast, people with PLAID do not have a reaction when they touch a cold object, like an ice cube. (The ice cube test is a common test for a cold allergy; it triggers a reaction in people with other forms of cold urticaria, which usually begin later in life than PLAID.) However, some people with PLAID do experience a burning sensation in their throats when they eat cold foods, like ice cream. In PLAID, the hives go away once the skin warms up. Prolonged exposure to cold can lead to loss of consciousness or a serious allergic reaction known as anaphylaxis.

Other skin problems can also occur in PLAID. A small number of affected individuals develop a blistering rash on the tip of their nose, ears, and fingers shortly after birth. The rash usually heals on its own in infancy, although in rare cases, it worsens over time. After the initial rash goes away, a different rash sometimes develops on the torso and limbs later in life. This rash, called a granuloma, can affect small patches of skin or be widespread. In people with PLAID, the granulomas do not occur in warm regions of the body, such as the armpits and other skin folds.

In many people with PLAID, immune system function is reduced, leading to recurrent infections such as frequent colds, ear infections, or bouts of pneumonia. The infections are likely related to lower-than-normal levels of special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM) or immunoglobulin G (IgG). Antibodies attach to specific foreign particles and germs, marking them for destruction. The number of immune system cells called natural killer (NK) cells may also be reduced.

Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs, can also occur. Autoimmune disorders associated with PLAID include autoimmune thyroiditis and vitiligo. Autoimmune thyroiditis results from damage to the butterfly-shaped, hormone-producing gland in the lower neck (the thyroid). Vitiligo is caused by attacks on the pigment cells in the skin, resulting in a patchy loss of skin coloration. Most people with PLAID have abnormal antibodies called autoantibodies in their blood. One such antibody common in people with PLAID is known as antinuclear antibody (ANA). Autoantibodies attach to normal proteins and can trigger an immune attack against the body's own tissues. However, not everyone with these abnormal antibodies has an autoimmune disease.