Test ID CD40 B-Cell CD40 Expression by Flow Cytometry, Blood
Ordering Guidance
This test is not used to detect in CD40L expression (CD154), which is responsible for X-linked hyper-IgM syndrome (HIGM1); see XHIM / X-Linked Hyper IgM Syndrome, Blood.
Shipping Instructions
Specimens are required to be received in the laboratory weekdays and by 4 p.m. on Friday. Collect and package specimen as close to shipping time as possible.
It is recommended that specimens arrive within 24 hours of collection.
Samples arriving on the weekend and observed holidays may be canceled.
Necessary Information
Ordering physician name and phone number are required.
Specimen Required
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
Additional Information: For serial monitoring, it is recommended that specimens are collected at the same time of day.
Secondary ID
89009Useful For
Evaluating patients for hyper-IgM type 3 (HIGM3) syndrome due to defects in CD40, typically seen in patients less than 10 years of age
Assessing B-cell immune competence in other clinical contexts, including autoimmunity, malignancy, and transplantation
Method Name
Flow Cytometry
Reporting Name
CD40 by Flow, QL, BSpecimen Type
Whole Blood EDTASpecimen Minimum Volume
1 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole Blood EDTA | Ambient | 72 hours | PURPLE OR PINK TOP/EDTA |
Clinical Information
The adaptive immune response includes both cell-mediated (mediated by T cells and natural killer [NK] cells) and humoral (mediated by B cells) immunity. After antigen recognition and maturation in secondary lymphoid organs, some antigen-specific B cells terminally differentiate into antibody-secreting plasma cells. Decreased numbers or aberrant function of B cells result in humoral immune deficiency states with increased susceptibility to infections, and these may be either primary (genetic) or secondary immunodeficiencies. Secondary causes include medications, malignancies, infections, and autoimmune disorders (this does not cause immunodeficiency with increased infection).
CD40 is a member of the tumor necrosis factor receptor superfamily, expressed on a wide range of cell types including B cells, macrophages, and dendritic cells.(1) CD40 is the receptor for CD40 ligand (CD40LG), a molecule predominantly expressed by activated CD4+ T cells. CD40/CD40LG interaction is involved in the formation of memory B lymphocytes and promotes immunoglobulin (Ig) isotype switching.(1) CD40LG expression in T cells requires cellular activation, while CD40 is constitutively expressed on the surface of B cells and other antigen-presenting cells.
Hyperimmunoglobulin M (hyper-IgM or HIGM) syndrome is a rare primary immunodeficiency characterized by increased or normal levels of IgM with low IgG and/or IgA.(2) Patients with hyper-IgM syndromes may have genetic variants in 1 of several known genes. Some of these genes are CD40LG, CD40, AICDA (activation-induced cytidine deaminase), UNG (uracil DNA glycosylase), and IKBKG (inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma; also known as NEMO).(2) Not all cases of hyper-IgM syndrome fit into these known genetic defects. Variants in CD40LG and IKBKG are inherited in an X-linked fashion, while variants in the other 3 genes are autosomal recessive in inheritance. Elevated IgM is only one of the features of NEMO deficiency and therefore, it is no longer classified exclusively with the hyper-IgM syndromes.
Distinguishing between the different forms of hyper-IgM syndrome is very important because of differing prognoses. CD40 and CD40LG deficiency are among the more severe forms, which typically manifest in infancy or early childhood, and are characterized by an increased susceptibility to opportunistic pathogens (eg, Pneumocystis carinii, Cryptosporidium, and Toxoplasma gondii).(3)
CD40 deficiency, also known as hyper-IgM type 3 (HIGM3), accounts for less than 1% of hyper-IgM syndromes. Flow cytometry analysis shows complete lack of CD40 expression on the B cells of these patients.(4) Intravenous injection with IgG is the treatment of choice along with immune reconstitution with hematopoietic cell transplantation. To date, all documented CD40-deficient patients have been diagnosed before age 1. Consequently, when used in the context of HIGM3, this test is only indicated in children (for diagnosis). In the case of CD40L deficiency, this test can be used for male patients or in female patients of child-bearing age (to identify carriers). A larger age spectrum has been reported with CD40L deficiency, ranging from infancy to early adulthood.
CD40 expression on B cells is also an indicator of immune status (eg, after the use of biological immunomodulatory therapy for autoimmune disease, cancer, and transplantation).
Reference Values
Present (normal)
Cautions
For questions about appropriate test selection, call 800-533-1710.
Day(s) Performed
Monday through Friday
Report Available
3 to 4 daysPerforming Laboratory

Test Classification
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
88184