Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation

Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) is a rare autosomal dominant autoinflammatory disease caracterized by early-onset recurrent erythematous plaques and vesiculopustular skin lesions associated with arthralgia, corneal erosions, and interstitial pneumonia. APLAID is an allelic disorder of PLCG2-associated antibody deficiency and immune dysregulation (PLAID) with some overlapping features. A recent study demonstrated that a family with an autoinflammatory disease was found to have point mutations in the same CSH2 domain of PLCG2. The patients identified with APLAID developed recurrent sinopulmonary infections presumably due to a lack of class-switched memory B cells on lymphocyte immunophenotyping. The patients were partially responsive to anakinra and to high-dose corticosteroids.

Immune system disease

PLCG2 [HSA:5336] [KO:K05859]

PMID:23711932

Almeida de Jesus A, Goldbach-Mansky R

Monogenic autoinflammatory diseases: concept and clinical manifestations.

Clin Immunol 147:155-74 (2013)
DOI:10.1016/j.clim.2013.03.016

PMID:26206677

Milner JD

PLAID: a Syndrome of Complex Patterns of Disease and Unique Phenotypes.

J Clin Immunol 35:527-30 (2015)
DOI:10.1007/s10875-015-0177-x

PMID:23887241

Milner JD, Holland SM

The cup runneth over: lessons from the ever-expanding pool of primary immunodeficiency diseases.

Nat Rev Immunol 13:635-48 (2013)
DOI:10.1038/nri3493

PMID:23000145

Zhou Q, Lee GS, Brady J, Datta S, Katan M, Sheikh A, Martins MS, Bunney TD, Santich BH, Moir S, Kuhns DB, Long Priel DA, Ombrello A, Stone D, Ombrello MJ, Khan J, Milner JD, Kastner DL, Aksentijevich I

A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2, causes a dominantly inherited autoinflammatory disease with immunodeficiency.

Am J Hum Genet 91:713-20 (2012)
DOI:10.1016/j.ajhg.2012.08.006