Mechanisms of Regulated and Dysregulated CARD11 Signaling in Adaptive Immunity and Disease.

CARD11 functions as a key signaling scaffold that controls antigen-induced lymphocyte activation during the adaptive immune response. Somatic mutations in CARD11 are frequently found in Non-Hodgkin lymphoma, and at least three classes of germline CARD11 mutations have been described as the basis for primary immunodeficiency. In this review, we summarize our current understanding of how CARD11 signals, how its activity is regulated, and how mutations bypass normal regulation to cause disease.

Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11).

Background: Combined immunodeficiency (CID) is a T-cell defect frequently presenting with recurrent infections, as well as associated immune dysregulation manifesting as autoimmunity or allergic inflammation.

Objective: We sought to identify the genetic aberration in 4 related patients with CID, early-onset asthma, eczema, and food allergies, as well as autoimmunity.

Methods: We performed whole-exome sequencing, followed by Sanger confirmation, assessment of the genetic variant effect on cell signaling, and evaluation of the resultant immune function.