Specific antibody deficiency

Clinical presentation

Recurrent ear infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in people with SAD. Some individuals show an increased frequency of infection beginning in the first years of life. In others, the onset of infections may occur later. In general, the infections in individuals with SAD are not as severe as those who have combined deficiencies of IgG, IgA, and IgM, like X-linked agammaglobulinemia (XLA) or common variable immune deficiency (CVID). Some, however, may present with a single severe pneumonia or other infection at the time of diagnosis.

Diagnosis

Problems with specific antibody production may be suspected in children and adults who have a history of recurrent infections of the ears, sinuses, bronchi, and/or lungs. The recommended evaluation usually includes measurement of total immunoglobulins, and antibody levels to specific bacteria such as tetanus, diphtheria, and/or Streptococcus pneumoniae.

When total immunoglobulins are low, a more profound immunodeficiency may be present. If isolated low antibody levels to Streptococcus pneumoniae are found during the initial evaluation, a pneumococcal vaccine (Pneumovax) is administered and follow-up levels are measured. Individuals older than 1 year of age may be immunized with the pneumococcal polysaccharide vaccine (Pneumovax 23 or Pnuimmune 23). These vaccines have the ability to induce protective antibody levels to 23 strains (serotypes) of Streptococcus pneumoniae. Antibody levels are measured again 4-6 weeks later to determine if adequate protective antibody levels were produced. Individuals without PI respond to a majority of the serotypes in these vaccines and retain those protective levels for years after receiving them. Antibody responses may not last as long in young children.

For therapy, it is also possible to re-immunize with Prevnar 13, a conjugate type of pneumococcal vaccine, which, for most, may be more immunogenic than Pneumovax. This vaccine, however, cannot be used to diagnose SAD.

A classification for mild, moderate, and severe forms of SAD exists that factors in the individual's age and number of normal post-immunization serotypes to define immunologic severity. Responses in which children respond to <50% of serotypes and adults respond to <70% have a moderate form of SAD with an increased risk of upper/lower respiratory tract infections that may warrant treatment. In the experience of many clinical immunologists, however, a normal vaccine response for an individual consists of producing protective titers of antibodies to at least 50% of the serotypes present in the vaccine. Furthermore, there are individuals who may fall into a response zone between 50-70% that have significant infections that may warrant a trial of immunoglobulin (Ig) replacement therapy.

An additional subset of people have a memory phenotype, meaning they respond normally initially and subsequently lose protective levels within six months.

When interpreting pneumococcal levels, it is important to recognize the variability in testing methodology and subsequent results that may occur among different labs. This highlights the importance of using a detailed clinical history in addition to laboratory findings to guide the immunologic evaluation when considering a diagnosis of SAD.

Expectations

The outlook for individuals with SAD is generally good. Many children appear to outgrow their deficiency as they get older, usually by age 6. For those for whom the deficiency persists, the use of prophylactic antibiotics and, in certain circumstances, the use of Ig therapy may prevent serious infections and the development of impaired lung function, hearing loss, or injury to other organ systems.

The natural history of individuals with SAD is not completely understood. SAD seems to occur more often in children, probably due to a delay in the natural maturation of the immune response. Children may outgrow SAD over time.

Adults with similar symptoms and poor response to vaccination are less likely to improve over time. Similar to IgG subclass deficiencies, SAD may evolve into CVID. At the present time, it is not possible to determine which individuals will have the transient type of deficiency as opposed to permanent deficiency, or which individuals will progress to a more wide-ranging immunodeficiency, such as CVID. For these reasons, periodic reevaluation of immunoglobulin levels and specific antibody levels is necessary.