Interpretation

Quantitative Lymphocyte Subsets: T, B, and NK :

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.