Antibody Deficiency, Humoral Immunodeficiency Workup

Workup of suspected antibody (humoral) immunodeficiency in a patient with recurrent sinopulmonary infections. Routes by quantitative immunoglobulins and specific antibody function: normal total Ig with impaired pneumococcal (polysaccharide) response defines specific antibody deficiency (SAD); low IgG with low IgA/IgM, poor vaccine response, and secondary causes excluded defines CVID. Emphasizes excluding secondary hypogammaglobulinemia and interpreting diagnostic vaccination correctly.

Evidence tier: Guideline-derived.

Decision points

  • Are total immunoglobulins (IgG/IgA/IgM) reduced?
  • Secondary cause excluded and CVID criteria met?

Do-not-miss pitfalls

  • Always exclude SECONDARY hypogammaglobulinemia before diagnosing a primary antibody deficiency, drugs (rituximab, antiepileptics, steroids), protein loss (nephrotic/PLE), and malignancy (CLL, myeloma, thymoma/Good syndrome) are common and treatable causes.
  • Do not measure vaccine responses within ~6 months of immunoglobulin replacement, passive antibody confounds interpretation. Assess specific antibody function BEFORE starting replacement when feasible.
  • Specific antibody deficiency (SAD) has NORMAL total immunoglobulins with an impaired polysaccharide (pneumococcal) response, it is missed if only quantitative Ig levels are checked. Functional vaccine-response testing is required.
  • Interpret the pneumococcal response by serotype-specific protective titers (≥1.3 µg/mL) to an age-appropriate proportion of serotypes, not by total anti-pneumococcal antibody. Use the linked PPSV23 calculator.
  • Polysaccharide responses mature with age, a poor PPSV23 response in young children may be developmentally normal; re-test over time before labeling a persistent SAD.
  • CVID morbidity is driven as much by NON-infectious complications (autoimmune cytopenias, GLILD, enteropathy, lymphoma) as by infections, screen for and manage these, not just infection prevention.
  • Titrate immunoglobulin replacement to clinical control of infections and an adequate IgG trough, the goal is breakthrough-infection prevention, individualized, not a fixed number alone.
  • Avoid live vaccines in CVID and severe antibody deficiency, and in patients on immunoglobulin replacement; use conjugate (not just polysaccharide) pneumococcal vaccination.

Evidence & citations

  1. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.e78. PMID 26371839
  2. Orange JS, Ballow M, Stiehm ER, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the AAAAI. J Allergy Clin Immunol. 2012;130(3 Suppl):S1-S24. PMID 22935624
  3. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1-S46. PMID 28041678
  4. Bonilla FA, Barlan I, Chapel H, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38-59. PMID 26563668
  5. Perez EE. Diagnosis and management of specific antibody deficiency. Immunol Allergy Clin North Am. 2020;40(3):499-510. PMID 32654695

Clinician decision support. Verify against the cited source. Not a substitute for clinical judgment. 100% on-device; no patient data is stored or transmitted.