Specific Antibody Deficiency: Controversies in Diagnosis and Management

Abstract

Specific antibody deficiency (SAD) is a primary immunodeficiency disease characterized by normal immunoglobulins (Igs), IgA, IgM, total IgG, and IgG subclass levels, but with recurrent infection and diminished antibody responses to polysaccharide antigens following vaccination. There is a lack of consensus regarding the diagnosis and treatment of SAD, and its clinical significance is not well understood. Here, we discuss current evidence and challenges regarding the diagnosis and treatment of SAD. SAD is normally diagnosed by determining protective titers in response to the 23-valent pneumococcal polysaccharide vaccine. However, the definition of an adequate response to immunization remains controversial, including the magnitude of response and number of pneumococcal serotypes needed to determine a normal response. Confounding these issues, anti-polysaccharide antibody responses are age- and probably serotype dependent. Therapeutic strategies and options for patients with SAD are often based on clinical experience due to the lack of focused studies and absence of a robust case definition. The mainstay of therapy for patients with SAD is antibiotic prophylaxis. However, there is no consensus regarding the frequency and severity of infections warranting antibiotic prophylaxis and no standardized regimens and no studies of efficacy. Published expert guidelines and opinions have recommended IgG therapy, which are supported by observations from retrospective studies, although definitive data are lacking. In summary, there is currently a lack of evidence regarding the efficacy of therapeutic strategies for patients with SAD. We believe that it is best to approach each patient as an individual and progress through diagnostic and therapeutic interventions together with existing practice guidelines.

The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex

“…Similar to specific antibody deficiency (SAD) ( 105 ), poor humoral immune responses are observed in most BENTA patients in response to T cell-independent vaccines such as pneumococcal and meningococcal polysaccharide vaccines, even with repeated boosts. Some patients also fail to mount lasting protective titers to T cell-dependent conjugate vaccines for pneumococcal bacteria (i.e., Prevnar), varicella-zoster virus (VZV), or measles.…”

Using only a subset of pneumococcal serotypes is reliable for the diagnosis of specific antibody deficiency in children: A proof‐of‐concept study

“…2,3 The diagnosis of SAD requires the documentation of an adequate response to polysaccharide antigens measured by immune response to the 23-polyvalent pneumococcal vaccine (Pneumovax®, 23-PPV) and exclusion of other causes of immunodeficiency. 4,5 Measurement of antibody responses to all serotypes in 23-PPV may not be available in all facilities, and thus, a limited set of pneumococcal serotypes are often used to diagnose SAD. 6 Based on previous studies that demonstrated differences in the immunogenicity among pneumococcal serotypes, 7,8 we hypothesized that a narrower panel of serotype-specific antipneumococcal antibody titers would provide comparable diagnostic utility for SAD diagnosis as the complete panel of 23 serotypes.…”

Humoral immunodeficiencies: conferred risk of infections and benefits of immunoglobulin replacement therapy

“…45,46 Systemic, invasive, or opportunistic infections are uncommon. 47 If warranted by the frequency and severity of infections, patients with SAD may be managed with prophylactic antibiotics or Ig replacement therapy.…”