miércoles, 22 de julio de 2015

PLCG2-associated Antibody Deficiency and Immune Dysregulation (PLAID)

PLAID and PLAID-like diseases are rare immune disorders with overlapping features, and an allergic response to cold, called cold urticaria, is the most distinct symptom.

Causes

PLAID is a genetic disorder caused by mutations in the phospholipase C-gamma2 (PLCG2) gene, which is involved in the activity of specific immune cells, including B cells, NK cells, and myeloid cells. PLAID was discovered by NIAID scientists in 2012.

PLAID-like disease refers to a disorder that resembles PLAID, but mutations in PLCG2 have not been identified. Mutations in other genes that regulate immune activity along with PLCG2 are likely responsible, and research on PLAID-like disease is ongoing.

Signs and Symptoms

People with PLAID experience cold urticaria from infancy. This allergic response to cold tends to result from evaporative cooling, like exposure to cool air while sweating, and less so from touching cold objects. Additionally, some can develop a burn-like rash at birth in areas more likely to get cold, such as the nose.

Other symptoms include recurrent bacterial infections and skin granulomas, which are accumulations of inflammatory immune cells. Eating cold foods may cause a burning sensation in the throat or chest but does not progress to anaphylaxis.

Diagnosis

PLAID results in skin conditions that differ from other diseases that also cause cold urticaria. Some people with PLAID experience a blistering rash, almost resembling a burn, which develops during the first few days of life on the nose, ear, and fingertips. For most people, this rash resolves on its own, but in others, the rash worsens over time. As people age, they may develop skin granulomas.

People with PLAID tend to have high levels of anti-nuclear antibodies, which react against their own cells and tissues and increase the likelihood of developing an autoimmune disease. They also may be more susceptible to bacterial infections. However, some people experience cold urticaria and no other symptoms.

Low levels of IgA and IgM antibodies, low levels of NK cells, and a poor response to vaccination also may occur. Notably, people with PLAID lack abnormal proteins—cold agglutinins and cryoglobulins—observed in other cold-induced disorders.

Treatment and Research

Since PLAID was discovered in 2012, NIAID clinicians and scientists have continued their research in order to develop effective therapies and gain a better understanding of how the immune system functions. Currently, people with PLAID are advised to avoid triggers by warming rapidly after showers, avoiding drafts, and toweling off sweat. Antihistamines are used to treat allergic reactions.

The allergic response to cold likely results from abnormal activation of immune cells at low temperatures. NIAID researchers have shown that immune cells from PLAID patients, including mast cells, which release histamine; B cells; neutrophils; and monocytes, are abnormally activated by cold temperature. In the future, it may be possible to develop therapies that target the PLCG2 defect in order to restore normal immune function.