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Test ID: IABCS    
B-Cell Phenotyping Profile for Immunodeficiency and Immune Competence Assessment, Blood

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

Screening for common variable immunodeficiency (CVID) and hyper-IgM syndromes

 

Assessing B-cell subset reconstitution after stem cell or bone marrow transplant

 

Assessing response to B-cell-depleting immunotherapy

 

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

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.

The appropriate age-related reference values will be provided on the report.

Interpretation Provides information to assist in interpretation of the test results

T- and B-Cell Quantitation by Flow Cytometry:

When the CD4 count falls below 500 cells/mcL, HIV-positive patients can be diagnosed with AIDS and can receive antiretroviral therapy.

 

When the CD4 count falls below 200 cells/mcL, prophylaxis against Pneumocystis jiroveci pneumonia is recommended.

 

Immune Assessment B Cell Subsets, Blood:

The assay provides quantitative information on the various B-cell subsets (percentage and absolute counts in cells/microliter). Each specimen is evaluated for B-cell subsets with respect to the total number of CD19+ B cells present in the peripheral blood mononuclear cell population, compared to the reference range. In order to verify that there are no CD19-related defects, CD20 is used as an additional pan-B-cell marker (expressed as percentage of CD45+ lymphocytes).

 

The B-cell panel assesses the following B-cell subsets:

-CD19+=B cells expressing CD19 as a percent of total lymphocytes

-CD19+ CD27+=total memory B cells

-CD19+ CD27+ IgD+ IgM+=marginal zone or nonswitched memory B cells

-CD19+ CD27+ IgD- IgM+=IgM-only memory B cells

-CD19+ CD27+ IgD- IgM-=class-switched memory B cells

-CD19+ IgM+=IgM B cells

-CD19+ CD38+ IgM+=transitional B cells

-CD19+ CD38+ IgM-=plasmablasts

-CD19+ CD21-=CD21 low ("immature") B cells

-CD19+ CD21+=mature B cells

-CD19+ CD20+=B cells co-expressing both CD19 and CD20 as a percent of total lymphocytes

 

For isotype class-switching and memory B-cell analyses, the data will be reported as being consistent or not consistent with a defect in memory and/or class switching. If a defect is present in any of these B-cell subpopulations, further correlation with clinical presentation and additional functional, immunological, and genetic laboratory studies will be suggested.

 

Since each of the 11 B-cell subsets listed above contributes to the diagnosis of common variable immunodeficiency (CVID) and hyper-IgM syndromes and provides further information on the likely specific genetic defect, all the B-cell subsets are carefully evaluated to determine if further testing is needed for confirmation, including functional assays and genotyping, which is then suggested as follow-up testing in the interpretive report as detailed below.

 

If abnormalities are found in the B-cell phenotyping panel, the specimen will be reflexed to the CVID confirmation panel for assessment of defects in surface expression of B-cell-activating factor receptor (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) (2 genes/proteins associated with CVID). To conclusively determine if TACI mutations are present, the TACI mutation analysis test by gene sequencing can be ordered (TACIF / Transmembrane Activator and CAML Interactor [TACI] Gene, Full Gene Analysis).      

 

CVID Confirmation Flow Panel:

BAFF-R is normally expressed on over 95% of B cells, while TACI is expressed on a smaller subset of B cells and a proportion of activated T cells.

 

The lack of TACI or BAFF-R surface expression on the appropriate B-cell population is consistent with a CVID defect.

 

Results will be interpreted in the context of the B-cell phenotyping results and correlation to clinical presentation will be recommended.

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

This assay and the reference range reported are based on analysis of B cells derived from the mononuclear cell fraction of peripheral whole blood and, therefore, results may not be identical to those performed on whole blood (eg, TBBS / T- and B-Cell Quantitation by Flow Cytometry).

 

This test is a screening test and further analyses will be required to complete a diagnostic workup for common variable immunodeficiency (CVID) (eg, CVID / Common Variable Immunodeficiency Confirmation Flow Panel; TACIF / Transmembrane Activator and CAML Interactor [TACI] Gene, Full Gene Analysis) and hyper-IgM (XHIM / X-Linked Hyper IgM Syndrome, Blood and CD40 / B-Cell CD40 Expression by Flow Cytometry, Blood for CD40 ligand and CD40 expression, respectively).

 

This test is not indicated for the evaluation of lymphoproliferative disorders (eg, leukemia, lymphoma, multiple myeloma).

 

Timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets. See data under Clinical Information.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

T- and B-Cell Quantitation by Flow Cytometry:

1. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract B11052

2. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009;113(21):5134-5143

3. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411

4. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med 1997;59:42-50

5. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151

6. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516

7. Mandy FF, Nicholson JK, McDougal JS: Guidelines for performing single-platform absolute CD4+T-cell determinations with CD45 gating for persons infected with human immunodeficiency virus. Center for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 2003;52:1-13

8. Centers for Disease Control: 1997 Revised guidelines for performing CD4+ T-cell determinations in persons infected with human immunodeficiency virus (HIV). MMWR Morb Mortal Wkly Rep 46 no. RR-2: 1997, pp 1-29

9. U.S. Department of Health and Human Services: Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 43 no. RR-3: 1994, pp 1-21

 

Immune Assessment B Cell Subsets, Blood:

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;99:1544-1551

2. Brouet JC, Chedeville A, Fermand JP, Royer B: Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol 2000;30:2516-2520

3. Wehr C, Kivioja T, Schmitt C, et al: The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 2008;111:77-85

4. Alachkar H, Taubenheim N, Haeney MR, et al: Memory switched B-cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol 2006;120:310-318

5. Lee WI, Torgerson TR, Schumacher MJ, et al: Molecular analysis of a large cohort of patients with hyper immunoglobulin M (hyper IgM) syndrome. Blood 2005;105:1881-1890

 

CVID Confirmation Flow Panel:

1. Grimbacher B, Hutloff A, Schlesier M, et al: Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 2003;4(3):261-268

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

3. van Zelm M, Reisli I, van der Burg M, et al: An antibody-deficiency syndrome due to mutations in the CD19 gene. New Engl J Med 2006;354:1901-1912

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

5. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract B11052

6. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009 (prepublished online March 17, 2009)

7. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411

8. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Pyschosom Med 1997;59:42-50

9. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151

10. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516

11. 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;99:1544-1551