PLCG2-associated Antibody Deficiency and Immune Dysregulation (PLAID)

PLCG2-associated antibody deficiency and immune dysregulation (PLAID) and PLAID-like diseases are rare, inherited immune disorders with overlapping features. An allergic response to cold, called cold urticaria, is the most distinct symptom.

Discovered by NIAID scientists in 2012, PLAID is caused by mutations in the PLCG2 gene, which is involved in the activity of specific immune cells, including B cells, natural killer cells, and myeloid cells. PLAID-like diseases refer to disorders that resemble 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 diseases is ongoing.

People with PLAID experience cold urticaria, an allergic response of the skin to cold temperatures, from infancy. Watch this time-lapse video of an allergic reaction to cold.

Additionally, some individuals with PLAID can develop a burn-like rash at birth in areas most likely to be exposed to cold temperatures, such as the nose. People with PLAID may also have recurrent bacterial infections, autoimmune symptoms and an increased likelihood of developing an autoimmune disorder, and a burning sensation in the throat when eating cold foods.

No treatments that target the underlying cause of PLAID and PLAID-like diseases exist, so people with PLAID are advised to avoid allergic 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 are abnormally activated by cold temperature. In the future, it may be possible to develop therapies that target the PLCG2 defect to restore normal immune function.

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