Antibody studies – Interpretation of vaccine responses and identification of immunodeficiencies

Measurement of antibody responses to vaccines is widely used as a diagnostic laboratory tool for the identification of immunodeficiency.

When immunodeficiency is suspected based on the clinical presentation, antibody concentrations resulting from previous vaccinations or infections should be assessed:

  • tetanus (2738 S-ClteAb)
  • diphtheria (1253 S-CodiAb)
  • pneumococcal (6297 S-SpnAbVT or 6296 S-SpnAbNV)
  • Haemophilus influenzae type b (3585 S-HibAb), if the patient is known to have been vaccinated

If protective antibody levels are not present, vaccine responses to these antigens should be evaluated.

Instructions for measuring vaccine responses

  • Vaccine responses should be assessed from serum samples obtained immediately before vaccination and at least 4 weeks, but no later than 2 months, after vaccination.
  • At least 4 months, preferably 6 months, should have elapsed since the last IgG therapy before reliable evaluation.

Limitations in interpretation

  • If the patient has received significant doses of glucocorticoids or immunomodulatory IgG within the preceding 6–12 months, the response may be secondarily reduced.
  • Following high-dose immunoglobulin therapy, responses may remain suppressed for up to 9 months after treatment cessation.

T cell–dependent and T cell–independent B cell responses

B cells are activated upon encountering an antigen (protein or polysaccharide) that binds to their surface receptor. Activated B cells differentiate into plasma cells that produce antibodies.

B cells may be activated directly or via T-cell help.

In T cell–dependent responses, T cells recognize antigen presented by antigen-presenting cells and enhance antibody production. Protein antigens such as tetanus and diphtheria induce T cell–dependent responses. Tetanus generally elicits stronger responses than diphtheria.

Pneumococcal polysaccharide antigens induce immune responses by directly stimulating B cells without T-cell involvement. These responses are short-lived, with antibody levels declining to baseline typically within 3–8 years. Booster doses do not enhance responses, as polysaccharide vaccines do not induce immunological memory. In children under two years, polysaccharide vaccines are poorly immunogenic.

The Hib vaccine is a conjugate vaccine in which the polysaccharide is linked to a carrier protein, enabling a T cell–dependent response. However, Hib response cannot be used as a surrogate marker for protein antigen responses.

B cell responses in immunodeficiency

In laboratory diagnostics, vaccine-induced B cell responses are evaluated. Tetanus and diphtheria antibodies reflect T cell–dependent responses, while pneumococcal responses reflect T cell–independent function.

In combined immunodeficiency, both response types are impaired.

In primary antibody deficiencies, antibody production or function is impaired. Responses to polysaccharide antigens are particularly deficient.

Immunological findings in antibody deficiencies

  • In common variable immunodeficiency (CVID), serum concentrations of IgG as well as IgA and/or IgM are reduced. Approximately 90% of patients also have low IgE levels. The age of onset ranges from early childhood to late adulthood.
  • In agammaglobulinaemia, measurable antibody levels are essentially absent, and B cells are (almost) completely absent from the circulation. Symptoms typically begin in early childhood, when maternally derived antibodies transferred عبر placenta are lost.
  • In hyper-IgM syndromes, serum IgM levels are normal or elevated, whereas other immunoglobulin classes are absent. B-cell phenotyping shows either absence of class-switched memory B cells (AICDA, UNG) or absence of all CD27+ B cells (CD40, CD40L).
  • If antibody levels are decreased but vaccine responses are normal, the condition is not considered a severe immunodeficiency. In such cases of non-specific hypogammaglobulinaemia, severe infections are generally uncommon, and there is no clear evidence that immunoglobulin replacement therapy prolongs survival.
  • In some cases, antibody levels may be normal but vaccine responses impaired, with deficiency restricted to IgG subclasses, most commonly IgG2. This condition is referred to as specific antibody deficiency. The need for treatment and follow-up is determined based on the severity of the clinical presentation.

Clinical interpretation

Interpretation of vaccine responses in immunodeficiency diagnostics is based on expert recommendations and does not replace clinical judgement in individual patient management.