Page 474 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 32 Approach to the Evaluation of the Patient With Suspected Immunodeficiency 455

KEY CONCEPTS normally present in titers greater than 1 : 10; individuals with
Diagnosis of Immune Deficiencies poor antibody production may have low or absent titers. Specific
IgG antibody production can be measured following immuniza-
Features of Congenital antibody Deficiencies tion with protein antigens, such as toxoids derived from Tetanus
• Free of infections until 6–9 months of age, when maternal antibodies and Diphtheria organisms, and polysaccharide antigens, such as
that passed through the placenta to infant are below protective levels those produced by pneumococci and Haemophilus influenzae.
• Severe infections with bacterial organisms, especially sinusitis, otitis For pneumococcal immunization, there are two vaccines that
media, and pneumonias caused by encapsulated bacteria, such as need to be differentiated. The conjugated vaccine containing 13
Streptococcus pneumoniae pneumococcal serotypes (PREVNAR13, Wyeth) is currently
included in the universal schedule of immunizations for infants
Features of Congenital T-Cell Immunodeficiency and toddlers and induces a robust, T cell–dependent immune
• Onset of thrush, diarrhea, and failure to thrive in the first months of response. The unconjugated 23-valent pneumococcal polysac-
life
• Severe infections with opportunistic microorganisms, such as Pneu- charide vaccine (Pneumovax, Merck) is available for immunization
mocystis jiroveci, Candida albicans, adenovirus, cytomegalovirus (CMV), to adults and children aged 2 years and older. The immune
Epstein-Barr virus (EBV). “BCG-itis” in areas where Bacille Calmette- response for this vaccine is considered less dependent on T cells
Guérin (BCG) immunization is mandatory and also less lasting than the conjugated vaccine. The pneumococ-
• Absolute and relative lymphopenia cal antigen challenge using the unconjugated vaccine is not
recommended for children under 2 years of age because healthy
Screening Tests for Suspected Immunodeficiency children are not thought to reliably respond to the unconjugated
• Evaluation for neutropenia, lymphopenia, thrombocytopenia, and/or pneumococcal antigen at this age. However, this view has been
small platelets
• Immunoglobulin levels and specific antibodies to childhood challenged by data showing that 1-year-old children produce
13,14
immunizations normal antibody responses to this unconjugated vaccine.
• Lateral chest radiography in infants for thymus shadow Normal antibody responses are usually demonstrated with an
• Consider flow cytometry to quantify T cells, T-cell subsets, B cells, over twofold rise in specific antibody levels within 2–3 weeks
and natural killer (NK) cells (especially in infants) for protein antigens and within 4–6 weeks for polysaccharide
• Measurement of CH50 activity antigens. Patients with agammaglobulinemia are expected not
15
• Test for oxidative burst in phagocytes
to produce antibody responses, whereas others, such as those
with IgG2 subclass deficiency and normal levels of total IgG,
may only have difficulty with antibody production following
IgE level measurement is of significance for the diagnosis of immunization with polysaccharide antigens. Patients with selective
HIES. Serum IgG subclasses levels can be determined. However, IgA deficiency, alone or with transient hypogammaglobulinemia
rather than using IgG subclass levels to screen for immunode- of infancy, have normal specific IgG antibody production, by
ficiency, they are best utilized when patients have clinical condi- definition. The pneumococcal serotypes included in the current
tions associated with specific antibody deficiencies but normal conjugated antipneumococcal vaccine, serotypes 1, 3, 4, 5, 6A,
total IgG levels. In some of these patients, IgG subclass deficiency, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, were estimated to be
particularly IgG2 and IgG3 deficiencies, might be present. IgG2 responsible for approximately 90% of invasive pneumococcal
16
subclass deficiency has been linked with selective IgA deficiency disease in children less than 5 years of age worldwide. Previous
and deficiency of antipolysaccharide antibodies. IgA subclass immunization with the conjugate vaccine does not preclude use
low levels, IgA1, IgA2, have not been associated with a specific of the unconjugated pneumococcal polysaccharide vaccine. The
immune defect, and there is no validity for measuring these. 23-valent polysaccharide vaccine provides the potential for
The variation of normal ranges of human serum Igs with age stimulation and measurement of a protective immune response
is an important consideration in children, since IgA and IgG to additional 11 serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20,
subclass levels may not reach normal adult reference ranges until 22F, 33F) not included in the conjugated vaccine. Testing for
6 years of age. 1 antibodies against serotypes not included in the two vaccines
and comparing the antibody titers in the pre- and postimmuniza-
B-Cell Function: Specific Antibody Production tion blood samples helps in the assessment of specific increase
To properly assess B-cell function, specific antibody production of particular antiserotype antibody titers as a response to the
must be measured. Patients with normal Ig and Ig subclass levels vaccine administration.
might exhibit deficient antigen-dependent antibody responses.
An initial screen of antibody production may involve the quan- Evaluation of Cellular Immunity
tification of isohemagglutinins. Isohemagglutinins occur in all Cellular immune function had been historically screened with
individuals except those with blood type AB; isohemagglutinins the use of the delayed-type hypersensitivity (DTH) skin tests.
are natural IgM antibodies to polysaccharide blood group antigens DTH reactions occur 48–72 hours after antigen exposure, although
A and/or B, which are not expressed in the red blood cells (RBCs) antigens used to test DTH can occasionally produce immediate
of the patient tested. Individuals form isohemagglutinins as a hypersensitivity reactions. The clinical response and time of
result of environmental exposure to ubiquitous antigens that observation were to discriminate between immediate and delayed
share epitopes with blood antigens. Children less than 1 year of reactions. DTH reactions involve the production of local edema
age do not reliably have measurable serum isohemagglutinins and vasodilation as a result of inflammatory cytokines secreted
because of the limited exposure to the environment. A patient by antigen-specific T cells, followed by lymphocyte infiltration
with blood type A should have anti-B IgM; patients with blood and maximal induration 48 hours after antigen intradermal
type B should have anti-A IgM; and patients with blood type O injection of an antigen. Generally, DTH skin tests are performed
should have both anti-A and anti-B IgM. These antibodies are using vaccine antigens or microbial agents to which the patient