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HelpTest Code XHIM X-Linked Hyper IgM Syndrome, Blood
Reporting Name
X-Linked Hyper IgM Syndrome, BUseful For
Screening for X-linked hyper-IgM (XL-HIGM) or CD40L deficiency, primarily in male patients younger than 10 years
Ascertaining XL-HIGM carrier status in women of child-bearing age (younger than 45 years)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
WB Sodium HeparinShipping Instructions
Testing performed Monday through Friday. Specimens not received by 4 p.m. Central time on Fridays may be canceled.
Specimens arriving on the weekend and observed holidays may be canceled.
Collect and package specimen as close to shipping time as possible. It is recommended that specimens arrive within 24 hours of collection.
Necessary Information
The ordering healthcare professional's name and phone number are required.
Specimen Required
Container/Tube: Green top (sodium heparin)
Specimen Volume: 4 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
Additional Information: For serial monitoring, it is recommended that specimen collection be performed at the same time of day.
Specimen Minimum Volume
1.2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| WB Sodium Heparin | Ambient | 72 hours | GREEN TOP/HEP |
Reference Values
Present
Day(s) Performed
Monday through Friday
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-Flow cytometry, cell surface, cytoplasmic
88185 x 6-Each additional marker
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| XHIM | X-Linked Hyper IgM Syndrome, B | 98239-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 82964 | CD40 Ligand Expression | 98240-5 |
| 29040 | CD40muIg (Function) | 98241-3 |
| 23901 | Interpretation | 69052-9 |
Clinical Information
CD154 (CD40 ligand: CD40L) is required for the interaction of T cells and B cells as part of the normal adaptive immune response. Activation of T cells leads to the expression of the CD40L molecule on the cell surface. CD40L binds the CD40 receptor that is constitutively expressed on B cells, monocytes, and macrophages. Interaction of CD40L with CD40 is important in B-cell proliferation, differentiation, and class-switch recombination (isotype class-switching).
Patients with X-linked hyper-IgM (XL-HIGM) syndrome have defective CD40L expression on their activated helper CD4 T cells.(1,2) It is the most common class switch recombination defect and accounts for approximately 50% of the patients in this category. It leads to defective B-cell responses and the absence of immunoglobulin class-switching, which are typified by a profound reduction or absence of isotype class-switched memory B cells (CD19+CD27+IgM-IgD-) with low or absent secreted IgG and IgA and normal or elevated serum IgM levels.(1,2) Due to the impairment of T-cell function and macrophage activation, patients with XL-HIGM are particularly prone to opportunistic infections with Pneumocystis jiroveci, Cryptosporidium, and Toxoplasma gondii.(1)
A defect in surface expression of CD40L on activated CD4 T cells can be demonstrated using an anti-CD40L antibody and flow cytometry.(3,4) Since certain CD40LG variants can maintain surface protein expression, albeit with loss of function, it is important to also evaluate CD40L-binding capacity to eliminate the possibility of false-negative results. A soluble recombinant, chimeric receptor protein, CD40-uIg, is incorporated into the assay, which assesses CD40L function by determining receptor-binding activity. Approximately 20% of patients with XL-HIGM have activated CD4 T cells with normal surface expression of CD40L but aberrant function.(4)
XL-HIGM is a severe primary immunodeficiency that affects male patients, and most patients are diagnosed within a few months to the first year of life. Female patients are typically carriers and asymptomatic. Consequently, this test is only indicated for boys (<10 years) or to identify carriers, women of child-bearing age (<45 years).
Interpretation
This is a qualitative assay; CD40L-protein expression and function are reported as present or absent. Absence of CD40L-protein expression and function is consistent with X-linked hyper-IgM (XL-HIGM). In female patients, the presence of 2 populations-normal and abnormal-is consistent with carrier status.
Most patients (80%-90%) with XL-HIGM have absent or significantly reduced CD40L expression on their activated CD4 T cells. Patients with normal CD40L expression, but abnormal function, show an absence of binding with soluble chimeric CD40-uIg antibody, substantiating a diagnosis of XL-HIGM. Female patients who are carriers for this disease will show a typical bimodal pattern of CD40L expression, with 50% of the T cells lacking any CD40L expression. In the case of aberrant protein function, a similar profile will be obtained with the CD40-uIg antibody.
CD69 is a marker for T-cell activation and serves as a positive control; in the absence of induced CD69 expression on T cells, the presence of XL-HIGM cannot be assessed.
Report Available
3 to 4 daysSpecimen Retention Time
4 daysReject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
Method Name
Flow Cytometry
Genetics Test Information
CD40LG is located on the long arm of the X-chromosome (Xq 21.3-22) and encodes the surface protein CD40 ligand (CD154). It is critical for the formation of germinal centers and, therefore, class switch recombination and somatic hypermutation. More than 100 unique genetic variants of CD40LG have been described. The observed variants are scattered throughout the gene but are more prevalent in exon 5.