Deleterious germline CARD11 gain-of-function variants alter human B-cell and CD4+ T-cell differentiation and function
Clicks: 6
ID: 317146
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
1.5
/100
6 views
1 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #14 of 30 articles by views in Clinical & Experimental Immunology
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Introduction CARD11 is a scaffold protein expressed primarily in hematopoietic tissues, shaping key processes in B and T cells via regulation of Ag-linked signaling pathways including NF-κB, mTOR, JNK, and AKT. Heterozygous, gain-of-function (GOF) variants in its encoding gene, CARD11, are implicated in a human disorder characterized by frequent upper respiratory infections, poor responses to polysaccharide vaccines, vulnerability to certain opportunistic viruses, and polyclonal B-cell expansion, likely predisposing these patients to lymphoma. Over the past decade, several studies have elucidated some of the B-cell functional defects that likely underlie the patients’ infectious phenotype. However, the potential contributions of CARD11 GOF variants to subpopulations of T cells have not been explored in detail. Methods Our study sought to investigate the effect of increased CARD11 activity on the development, maturation, activation, differentiation and effector function of adaptive lymphocytes from a cohort of five individuals harboring monoallelic CARD11 GOF variants through detailed ex vivo immunophenotyping and in vitro analyses. Results Our findings revealed intrinsic requirements for CARD11 in activation, differentiation and effector function of human naïve B cells. Contrary to previous reports, intact CARD11 activity is also required for multiple aspects of CD4+ T-cell homeostasis alongside its notable role in the humoral immune response. Conclusions Our findings shed light on mechanisms underlying disease pathogenesis due to not only CARD11 GOF variants but also LOF variants and reveal opportunities to consider targeted therapies in CARD11 GOF patients.
| Reference Key |
openalex_W7164531626
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Tina Nguyen, Melissa A. Kallarakal, Jackie L. Ludgate, Ian M. Morison, Helen C Su, Swadinhya Arjunaraja, Andrew L. Snow, S. Cindy, Stuart G. Tangye |
| Journal | Clinical & Experimental Immunology |
| Year | 2026 |
| DOI |
10.1093/cei/uxag034
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.