**1. Introduction**

190 Immunodeficiency

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Specific antibody deficiency (SAD) is a common antibody immunodeficiency defined as a poor antibody response to unconjugated pneumococcal polysccharides present in the 23 valent pneumococcal vaccine (PPV23). Clinical manifestations of specific antibody deficiency include recurrent sinopulmonary infections, such as sinusitis, otitis media, bronchitis, and pneumonia. All immunoglobulin concentrations, including IgG subclasses, are normal, and antibody response to protein antigens (eg, tetanus toxoid, diphtheria toxoid) and the conjugate H influenzae b vaccine are also normal in most patients. [11, 44, 56] In some patients with SAD, the response to the pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) is also normal.

SAD was first reported in a small group of patients in the early 1980s. [6, 46] The widespread use of pneumococcal immunization to assess antibody responses has revealed that specific unresponsiveness to polysaccharide antigens is not unusual. [21, 25]

The vast majority of SAD patients have a deficiency of specific antibodies to polysaccharides but normal antibodies to protein antigens, resembling the developing immunologic status of human newborns and infants. Infants readily produce antibodies against vaccine proteins but fail to respond to most vaccine polysaccharides until approximately two years of age. In some patient with early onset SAD, this condition may represent a delayed maturation of the immune response to polysaccharides.

SAD is also found in association with many primary and secondary immunodeficiencies. An association of SAD with IgG subclass deficiencies, particulary IgG2 deficiencies, has been described. [9] IgG2 subclass deficient patients have antibody responses to a restricted number of polysaccharides in the PPV vaccine. Frequently, these patients also have poor immunological memory, with IgG antibody titers decreasing to pre-immunization levels within 6 to 12 months. [51]

© 2012 Sorensen et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Other primary immunodeficiency disorders with an immunologic phenotype associated with specific antibody deficiency include Wiskott-Aldrich syndrome, partial DiGeorge syndrome, asplenia, hyper-IgE syndrome, and selective IgA deficiency (without IgG subclass deficiency). [30] In addition, specific antibody deficiency can be identified in some patients with congenital dysmorphic syndromes or chromosomal abnormalities associated with recurrent sinopulmonary infections. Acquired or secondary immunodeficiencies associated with specific antibody deficiency include splenectomy, immunosuppression, chronic lung disease, protein-calorie malnutrition, and human immunodeficiency virus infection.

Selective Antibody Deficiency with Normal Immunoglobulins 193

The pneumococcal polysaccharide vaccine (PPV23) is not recommended for children under 24 months since the responses to polysaccharide antigens is considered absent or ineffective in the first 2 years of life. Pneumococcal polysaccharide vaccines (PPV23) are recommended

1 X X

3 X X 4 X X X 5 X X 6A X 6B X X X 7F X X

9V X X X

14 X X X

18C X X X 19A X X 19F X X X

23F X X X

23-PPV: 23-valent polysaccharide vaccine; 7-PCV: heptavalent conjugate vaccine; 13-PCV: 13-valent conjugate vaccine

**Table 1.** Pneumococcal vaccines and antibody testing for conjugate and pure pneumococcal

23-PPV 7-PCV 13-PCV

for in high risk patients over age 5 and for individuals over age 65. [1]

Vaccines

Serotypes

2 X

8 X 9N X

10A X 11A X 12F X

15B X 17F X

20 X 22F X

33F X

polysaccharides

PCV: 13-valent conjugate vaccine. *Courtesy of RU Sorensen, MD.*

There is not a single pathogenic mechanism for specific anti-polysaccharide antibody deficiencies. The variable conditions in which an inability to respond to polysaccharides is found suggest that many different immunologic phenotypes may lead to the same clinical phenotypic antibody deficiency. Further defining different SAD phenotypes and relating these phenotypes to associated conditions may shed further insight into possible pathogenic mechanisms.
