Test Catalog

Test Id : CVID

Common Variable Immunodeficiency Confirmation Flow Panel, Blood

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening for common variable immunodeficiency (CVID)

 

Identifying defects in TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BAFF-R (B-cell activating factor receptor) in patients presenting with clinical symptoms and other laboratory features consistent with CVID

 

Evaluating B cell immune competence by assessing expression of BAFF-R and TACI proteins

 

Assessing BAFF-R and TACI protein expression and frequency of B cells bearing these receptors

 

TNFRSF13C (BAFF-R) and TNFRSF13B (TACI) gene variants have been described in a small subset of patients with humoral immunodeficiencies classified as CVID. The majority of TNFRSF13B variants preserve TACI protein expression and require genetic testing to identify disease-causing or potentially disease-causing variants.

 

This test is not useful for general evaluation of immune competence.

Method Name
A short description of the method used to perform the test

Fluorescent Flow Cytometry

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CVID Confirmation Flow Panel

Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

Ordering Guidance

This test is preferable to order only when there is clear evidence for common variable immunodeficiency and/or evidence of dysregulated B-cell subsets. These can be obtained by ordering IABCS / B-Cell Phenotyping Profile for Immunodeficiency and Immune Competence Assessment, 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube: Lavender top (EDTA)

Specimen Volume: 10 mL

Pediatric (< or =14 years) Volume: 4 mL

Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

< or =14 years: 3 mL

>14 years: 5 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 Refrigerated (preferred) 48 hours PURPLE OR PINK TOP/EDTA

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening for common variable immunodeficiency (CVID)

 

Identifying defects in TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BAFF-R (B-cell activating factor receptor) in patients presenting with clinical symptoms and other laboratory features consistent with CVID

 

Evaluating B cell immune competence by assessing expression of BAFF-R and TACI proteins

 

Assessing BAFF-R and TACI protein expression and frequency of B cells bearing these receptors

 

TNFRSF13C (BAFF-R) and TNFRSF13B (TACI) gene variants have been described in a small subset of patients with humoral immunodeficiencies classified as CVID. The majority of TNFRSF13B variants preserve TACI protein expression and require genetic testing to identify disease-causing or potentially disease-causing variants.

 

This test is not useful for general evaluation of immune competence.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency with a prevalence of CVID of 1:25,000 to 1:50,000.(1) It has a bimodal presentation with a subset presenting in early childhood and a second set presenting between 15 and 40 years of age or even later. CVID is characterized by hypogammaglobulinemia usually involving most or all of the immunoglobulin classes (IgG, IgA, IgM, and IgE), impaired functional antibody responses, and recurrent sinopulmonary infections.(1) B-cell numbers are usually normal, although a minority of patients (5%-10%) have very low B-cell counts (<1% of peripheral blood leukocytes). It is reasonable to suspect a transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) defect in patients with low to absent IgA, low IgG, and low or normal IgM, along with splenomegaly, autoimmune cytopenias, autoimmune thyroiditis, and tonsillar hypertrophy. In TACI-deficient patients, there may be an increased risk for developing neoplasias such as non-Hodgkin lymphoma or other solid tumors. CD19 defects result in absence of B cells expressing CD19.(2) When an alternative B-cell marker such as CD20 is used, however, B cells can be detected in the blood of these patients.

 

Of all patients with CVID, 25% to 30% have increased numbers of CD8 T cells and a reduced CD4/CD8 ratio (<1).(1) A subset (5%-10%) exhibit noncaseating, sarcoid-like granulomas in different organs and also tend to develop a progressive T cell deficiency.(1) Patients with variants in the TACI gene (see below) are particularly prone to developing autoimmune disease, including cytopenias as well as lymphoproliferative disease.

 

The etiology of CVID is heterogeneous.(3,4) Variants of the gene that encodes TACI, TNFRSF13B (tumor necrosis factor receptor superfamily, member 13B), probably account for about 10% to 15% of all CVID cases.(3,5) Patients with variants in the TACI gene are particularly prone to developing autoimmune disease, including cytopenias, as well as lymphoproliferative disease. The other variants each have been reported in only a handful of patients. The etiopathogenesis is still undefined in more than 65% to 75% of CVID patients.(3)

 

A BAFF-R (B-cell activating factor receptor, encoded by the TNFRSF13C gene) defect should be suspected in patients with low to very low class switched and non-switched memory B cells and very high numbers of transitional B cells (see IABC / B-Cell Phenotyping Screen for Immunodeficiency and Immune Competence Assessment, Blood).(6) Class switching is the process that allows B cells, which possess IgD and IgM on their cell surface as a part of the antigen-binding complex, to produce IgA, IgE, or IgG antibodies. A TACI defect is suspected in patients with low IgA and low IgG with normal to low switched B cells, with autoimmune or lymphoproliferative manifestations or both, and normal B cell responses to mitogens.

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.

%CD19+TACI+: >3.4% 

%CD19+BAFF-R+: >90.2%

Reference values apply to all ages.

Interpretation
Provides information to assist in interpretation of the test results

B-cell activating factor receptor (BAFF-R) is normally expressed on over 95% of B cells, while TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) is expressed on a smaller subset of B cells (3%-70%) and some activated T cells. Expression on B cells increases with B-cell activation.

 

The lack of TACI or BAFF-R surface expression on B cells is suggestive of a potential common variable immunodeficiency (CVID)-associated defect if other features of CVID are present. The majority of TACI variants (>95%) preserve protein expression but abrogate protein function, hence the only way to conclusively establish a TACI alteration is to perform TNFRSF13B genetic testing.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test should not be ordered serially.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Warnatz K, Denz A, Drager R, et al: Severe deficiency of switched memory B cells (CD27+ IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002 Mar 1;99(5):1544-1551

2. van Zelm M, Reisli I, van der Burg M, et al: An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006 May 4;354(18):1901-1912

3. Salzer U, Grimbacher B: TACI deficiency - a complex system out of balance. Curr Opin Immunol. 2021 Aug;71:81-88. doi:10.1016/j.coi.2021.06.004

4. Ramirez NJ, Posadas-Cantera S, Caballero-Oteyza A, Camacho-Ordonez N, Grimbacher B. There is no gene for CVID - novel monogenetic causes for primary antibody deficiency. Curr Opin Immunol. 2021 Oct;72:176-185. doi:10.1016/j.coi.2021.05.010

5. Salzer U, Chapel HM, Webster AD, et al: Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005 Aug;37(8):820-828

6. Warnatz K, Salzer U, Gutenberger S, et al: Finally found: human BAFF-R deficiency causes hypogammaglobulinemia. Clin Immunol. 2005;115(Suppl 1):820

Method Description
Describes how the test is performed and provides a method-specific reference

Peripheral blood mononuclear cells are isolated and stained with CD19, TACI, (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and BAFF-R (B-cell activating factor receptor), each conjugated to a fluorochrome. After the staining with specific antibody, the cells are washed, fixed with paraformaldehyde, and then analyzed by flow cytometry on a BD FACSCanto instrument. The cell-surface expression is denoted as the percent of CD19+ B cells expressing TACI and BAFF-R.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

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.

3 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

PBMC: 7 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

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 Regional Manager. 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.

88184

88185 x 2

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
CVID CVID Confirmation Flow Panel 90415-1
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.
28121 CD19+ BAFF-R+ % of CD19 B cells 90418-5
28113 CD19+ TACI+ % of CD19 B cells 90422-7
28124 Interpretation 69052-9

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports