Test | Indications | Interpretation |
---|---|---|
Humoral immunity deficiency | ||
IgE level measurement | Abscesses | Levels are high in patients with abscesses and pneumatoceles ( hyper-IgE syndrome Hyper-IgE Syndrome Hyper-IgE syndrome is a hereditary combined B- and T-cell immunodeficiency characterized by recurrent staphylococcal abscesses of the skin, sinopulmonary infections, and severe pruritic eosinophilic... read more ), partial T-cell deficiencies, hyper-IgG4 related disease, allergic disorders, or parasitic infections. Levels may be high or low in patients with incomplete B-cell defects or deficiencies. Levels are absent in 75% of patients with CVID.† Isolated deficiency is not clinically significant. |
B-cell quantification via flow cytometry | Low Ig levels | < 1% B cells suggests X-linked agammaglobulinemia X-linked Agammaglobulinemia X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. (See also Overview... read more . 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¶ | Lymphopenia, suspected SCID Severe Combined Immunodeficiency (SCID) Severe combined immunodeficiency is characterized by low to absent T cells and a low, high, or normal number of B cells and natural killer cells. Most infants develop opportunistic infections... read more or complete DiGeorge syndrome DiGeorge Syndrome DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell immunodeficiency and hypoparathyroidism. Infants with DiGeorge syndrome have low-set ears, midline facial... read more | 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. | ||
† Data from Lawrence MG, Palacios-Kibler TV, Workman LJ, et al: Low serum IgE is a sensitive and specific marker for common variable immunodeficiency (CVID). J Clin Immunol 38(3):225–233, 2018. doi: 10.1007/s10875-018-0476-0 | ||
‡ 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. |