Test Id : CD40
B-Cell CD40 Expression by Flow Cytometry, Blood
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating patients for hyper-IgM type 3 (HIGM3) syndrome due to defects in CD40, typically seen in patients less than 10 years
Assessing B-cell immune competence in other clinical contexts, including autoimmunity, malignancy, and transplantation
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Homozygous variants in the CD40 gene cause autosomal recessive hyper-IgM syndrome type 3. The CD40 gene is located on chromosome 20q12-q13.2.
Method Name
A short description of the method used to perform the test
Flow Cytometry
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Hyper IgM
Specimen Type
Describes the specimen type validated for testing
Whole Blood EDTA
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
Testing performed Monday through Friday. Specimens not received by 4pm (CST) on Friday may be cancelled.
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 healthcare professional name and phone number are required.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
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.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
1 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood EDTA | Ambient | 72 hours | PURPLE OR PINK TOP/EDTA |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Evaluating patients for hyper-IgM type 3 (HIGM3) syndrome due to defects in CD40, typically seen in patients less than 10 years
Assessing B-cell immune competence in other clinical contexts, including autoimmunity, malignancy, and transplantation
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Homozygous variants in the CD40 gene cause autosomal recessive hyper-IgM syndrome type 3. The CD40 gene is located on chromosome 20q12-q13.2.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 usually shows a 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. Most 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.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Present (normal)
Interpretation
Provides information to assist in interpretation of the test results
This assay is qualitative; CD40 expression is reported as present (normal) or absent (abnormal). Normal B cells express surface CD40 on the majority of cells.
Hyper-IgM (HIGM3) syndrome patients typically do not express CD40 on the surface of B cells. Genotyping of CD40 is required for a definite diagnosis of HIGM3. Call 800-533-1710 for ordering assistance.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
For questions about appropriate test selection, call 800-533-1710.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Bishop GA, Hostager BS. The CD40-CD154 interaction in B cell-T cell liaisons. Cytokine Growth Factor Rev. 2003;14(3-4):297-309
2. Lee WI, Torgerson TR, Schumacher MJ, et al. Molecular analysis of a large cohort of patients with hyper immunoglobulin M (IgM) syndrome. Blood. 2005;105(5):1881-1890
3. Kutukculer N, Moratto D, Aydinok Y, et al. Disseminated cryptosporidium infection in an infant with hyper-IgM syndrome caused by CD40 deficiency. J Pediatr. 2003;142(2):194-196
4.Banday AZ, Nisar R, Patra PK et al. Clinical and immunological features, genetic variants, and outcomes of patients with CD40 Deficiency J Clin Immunol. 2023;44(1):17. doi:10.1007/s10875-023-01633-1.
5. Yazdani R, Fekrvand S, Shahkarami S, et al. The hyper IgM syndromes: Epidemiology, pathogenesis, clinical manifestations, diagnosis and management. Clin Immunol. 2019;198:19-30. doi:10.1016/j.clim.2018.11.007
Method Description
Describes how the test is performed and provides a method-specific reference
The assay involves a multicolor panel of antibodies for the following markers: CD45, CD19, and CD40. After staining, the red blood cells are lysed. The remaining cells are washed and analyzed by flow cytometry. The cell surface expression of CD40 in B cells (CD19+) is determined and expressed as being present or absent.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Friday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
88184
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| CD40 | CD40 by Flow, QL, B | 104694-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 89009 | CD40 by Flow, QL, B | 104694-5 |