Related Experiment Video
Updated: Jul 7, 2025
Murine Model of CD40-activation of B cells
Published on: March 5, 2010
Clinical and Immunological Features, Genetic Variants, and Outcomes of Patients with CD40 Deficiency
Aaqib Zaffar Banday1,2,3, Rahila Nisar4, Pratap Kumar Patra5
1Department of Pediatrics, Government Medical College (GMC), Srinagar, India.
Insights
CD40 deficiency, a rare inherited immune disorder, primarily causes severe infections and B cell defects. Hematopoietic stem cell transplantation (HSCT) offers a curative treatment option for patients with CD40 deficiency.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- CD40-CD40L signaling is vital for immune function, yet CD40 deficiency is less studied than CD40L deficiency.
- This review comprehensively characterizes CD40 deficiency, compiling data from reported cases.
Approach:
- A systematic literature review was conducted using PubMed, Embase, and Web of Science databases up to August 2023.
- Data extraction and analysis were performed using a standardized form and SPSS software.
Key Points:
- Forty CD40-deficient patients were identified, predominantly presenting with respiratory (93%) and gastrointestinal (57%) infections.
- Common infections included Cryptosporidium and Pneumocystis jirovecii; sclerosing cholangitis affected one-third of patients.
- Immunological hallmarks include low IgG, absent switch memory B cells, and often elevated IgM.
- Splice-site and missense variants were the most frequent genetic defects.
Conclusions:
- CD40 deficiency presents with severe infections and characteristic B cell abnormalities.
- Immunoglobulin replacement and antimicrobial prophylaxis are standard management.
- Hematopoietic stem cell transplantation (HSCT) is a potentially curative option, achieving success in 73% of recipients.
Purpose:
Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency.
Methods:
The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis.
Results:
Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients.
Conclusions:
We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.
Related Concept Videos
01:25Immunodeficiency Diseases
There are three main causes of immunodeficiency...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...