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Specific and Advanced Laboratory Tests for Immunodeficiency*

Specific and Advanced Laboratory Tests for Immunodeficiency*

Test

Indications

Interpretation

Humoral immunity deficiency

IgE level measurement

Abscesses

Levels may be high or low in patients with incomplete B-cell defects or deficiencies.

Isolated deficiency is not clinically significant.

B-cell quantification via flow cytometry

Low Ig levels

B cells are absent in Omenn syndrome.

Lymph node biopsy

For some patients with lymphadenopathy, to determine whether germinal centers are normal and to exclude cancer and infection

Interpretation varies by histology.

Genetic testing (genetic sequencing or mutation analysis)†

B cells < 1% (detected by flow cytometry)

Suspicion of a disorder with one or more characteristic mutations

Abnormalities in genes suggest or confirm a diagnosis, as in the following few of many examples:

Results can also provide prognostic information.

T-cell deficiency

T-cell enumeration using flow cytometry and monoclonal antibodies§

Interpretation varies by molecular type of SCID.

T-cell proliferation assays to mitogens, antigens, or irradiated allogeneic WBCs

Low percentage of T cells, lymphopenia, suspected SCID or complete DiGeorge syndrome

Low or absent uptake of radioactive thymidine during cell division indicates a T-cell or combined defect.

Detection of antigens (eg, class II MHC molecules) using monoclonal antibodies or serologic HLA typing

Suspected MHC deficiency, absence of MHC stimulation by cells

Absence of class I or class II HLA antigens by serologic HLA typing is diagnostic for MHC antigen deficiency.

RBC adenosine deaminase assay

Severe lymphopenia

Levels are low in a specific form of SCID.

Purine nucleoside phosphorylase assay

Severe persistent lymphopenia

Levels are low in combined immunodeficiency with normal or elevated Ig levels.

T-cell receptor and signal transduction assays

Phenotypically normal T cells that do not proliferate normally in response to mitogen antigen

Interpretation varies by test.

T-cell receptor excision circle (TREC) test

Screening for SCID and other T-cell disorders

Low numbers suggest a defect that disrupts development or maturation of T cells or that causes apoptosis of T cells.

Combined humoral and cellular immunity deficiencies

Genetic testing

A suspected combined immunodeficiency disorder

Abnormalities in genes suggest or confirm certain disorders; for example, abnormalities in NEMO suggest combined immunodeficiency with defects of NF–kappa B regulation, and abnormalities in IL-2RG suggest SCID.

Phagocytic cell defects

Assays for oxidant products (hydrogen peroxide, superoxide) or proteins (CR3 [CD11] adhesive glycoproteins, NADPH oxidase components)

History of staphylococcal abscesses or certain gram-negative or fungal infections (eg, Serratia marcescens, aspergillosis)

Abnormalities confirm phagocytic cell defects or deficiencies.

Phosphorylation assays for signal transducer and activator of transcription (STAT), including STAT1 and STAT4

Recurrent mycobacterial infections

This test is the first one done to check for Mendelian susceptibility to mycobacterial disease (MSMD).

Complement deficiency

Measurement of levels of specific complement components

Suspicion of a complement disorder

Interpretation varies by test.

* Some of these tests may be used for screening or initial testing.

† Genetic panels for primary immunodeficiencies and for specific diseases such as CVID or SCID are commercially available. For information on interpreting genetic studies in these disorders, see Chinn IK, Chan AY, Chen K, et al: Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 145(1):46–69, 2020. doi: 10.1016/j.jaci.2019.09.009

‡ SAP is also called SH2 domain protein 1A [SH2D1A], or DSHP.

§ Test uses anti-CD3 for all T cells, anti-CD4 for helper T cells, anti-CD8 for cytotoxic T cells, anti-CD45RO or anti-CD45RA for activated and naive T cells, anti-CD25 for regulatory T cells, and anti-CD16 and anti-CD56 for natural killer cells.

BTK = Bruton tyrosine kinase; CH = hemolytic complement; CR = complement receptor; CVID = common variable immunodeficiency; HLA = human leukocyte antigen; Ig = immunoglobulin; IL2RG = interleukin-2 receptor gamma; MHC = major histocompatibility complex; NADPH = nicotinamide adenine dinucleotide phosphate; NEMO = NF–kappa-B essential modifier; NF–kappa-B = nuclear factor-kappa-B; RBC = red blood cell; SAP = SLAM-associated protein; SCID = severe combined immunodeficiency; SLAM = signaling lymphocyte activation molecule; WBC = white blood cell.