Laboratory Evaluation of B cell Function

Laboratory Evaluation of B cell Function

What laboratory tests are performed to evaluate the integrity of the humoral immune system (B-cell function)?

A simple initial screen for hypogammaglobulinemia is to subtract the albumin from the total protein and see if it is <1.5 g/dL. A reasonable screen for the evaluation of B-cell function is to determine the serum IgA level and perform the inexpensive in vivo functional tests. If all these tests are normal, clinically significant B-cell dysfunction may be reasonably excluded. If IgE is normal, a class-switching defect is unlikely. If any of these tests are abnormal, further testing to characterize B cell development and referral to clinical immunology is appropriate. As with rheumatologic evaluations, further testing to diagnose a disease requires objective evidence for tissue or end-organ involvement.

Laboratory Evaluation of B cell Function

CategorySpecific TestsComments
In vivo functional tests (routine screening tests)Isohemagglutinin titers (anti-blood group A and B)Naturally occurring; predominantly IgM
Diphtheria and tetanus booster immunizationSerum antibodies assayed prior to and 2 weeks later; assesses capacity to synthesize IgG antibodies against protein antigens
Pneumococcal immunizationSerum antibodies assayed prior to and 3 weeks later; assesses capacity to synthesize antibodies against polysaccharide antigens. Currently no formal consensus on the reference ranges for normal.
Immunoglobulin quantitationIgM, IgG, IgA levelsVarious immunoassays may be used; readily available
IgG subclass, IgE levelsELISA and RIA available (expensive)
In vitro tests (expensive)Peripheral blood total B cellsFlow cytometry, CD19+ B cell numbers
B cell subsetsClass-switched memory B cells (CD27+ IgD-) versus non-switched memory B cells (CD27+ IgD+) and immature or transitional B cells
Genetic testing BTK (XLA), CVID, CID with monogenetic causeIn vitro immunoglobulin synthesisPeripheral blood mononuclear cells stimulated in vitro with pokeweed mitogen (not frequently for clinical decisions)

ELISA, enzyme-linked immunosorbent assay; RIA, radioimmunoassay.

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