Selective antibody deficiency with normal immunoglobulins (Ig) is characterized by deficient specific antibody response to polysaccharide antigens but not to protein antigens, despite normal or near-normal serum levels of immunoglobulins, including IgG subclasses. Treatment includes Pneumococcal conjugate vaccine and sometimes prophylactic antibiotics and immune globulin replacement therapy.
(See also Overview of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder).
Selective antibody deficiency with normal immunoglobulins (SADNI) is a primary immunodeficiency disorder. It is one of the most common immunodeficiencies that manifests with recurrent sinopulmonary infections. Selective antibody deficiencies can occur in other disorders, but SADNI is a primary disorder in which deficient response to polysaccharide antigens is the only abnormality (see table Humoral Immunity Deficiencies). The inheritance and pathophysiology have not been elucidated, but some evidence suggests that the cause may be inherited molecular abnormalities (1).
A subset of patients with SADNI initially have an appropriate response to polysaccharide antigen but lose antibody titers within 6 to 8 months (called SADNI memory phenotype).
Patients have recurrent sinopulmonary infections and sometimes manifestations that suggest atopy (eg, chronic rhinitis, atopic dermatitis, asthma). Severity of the disorder varies.
Young children may have a form of SADNI that resolves spontaneously over time.
General reference
1. Wood PM, Mayne A, Joyce H, Smith CI, Granoff DM, Kumararatne DS. A mutation in Bruton's tyrosine kinase as a cause of selective anti-polysaccharide antibody deficiency. J Pediatr 2001;139(1):148-151. doi:10.1067/mpd.2001.115970
Diagnosis of SADNI
Usually normal immunoglobulin levels (IgG, IgA, IgM, and IgG subclasses)
Deficient or absent response to polysaccharide vaccines
Because healthy children < 2 years can have recurrent sinopulmonary infections and weak responses to polysaccharide vaccines, testing for SADNI is not done unless patients are > 2 years. Then, levels of IgG, IgA, IgM, and IgG subclasses and responses to vaccines are measured. Laboratory testing shows a deficient response to polysaccharide vaccines (eg, pneumococcal vaccine) and a normal response to protein antigens (eg, tetanus toxoid, diphtheria toxoid) and/or conjugate vaccines (eg, Haemophilus influenzae type b).
Testing usually involves giving the 23-valent pneumococcal polysaccharide vaccine (PPSV23), with quantitative measurement of antibody response; most clinicians assess response to 12 to 14 subtypes of Streptococcus pneumoniae. Ideally, titers are done by the same laboratory both before and after vaccine administration. Response to each subtype is characterized by the degree of rise in titer and whether the titer is considered protective, defined as an antibody level ≥ 1.3 mcg/mL (1.3 mg/L).
A normal response to PPSV23 for children age 2 to 5 years is defined as protective antibodies to ≥ 50% of the subtypes tested, with at least a 2-fold increase in the titers; patients 6 to 65 years should have protective antibodies to ≥ 70% of subtypes. Patients with abnormal results can be classified phenotypically as follows (1):
Memory phenotype: Normal initial response to PPSV23, which is lost within 6 months.
Mild phenotype: Multiple serotypes (> 50% for children 2 to 5 years or > 30% for patients 6 to 65 years) without protective titers or without a 2-fold increase in titers
Moderate phenotype: Protective titers to ≥ 3 subtypes but fewer than the expected number for their age
Severe phenotype: Protective titers to ≤ 2 subtypes, and the titer, if present, tends to be low (< 1.3 to 2.0 mcg/mL [< 1.3 to 2.0 mg/L]).
Family members of patients know to have SADNI do not need screened unless they manifest a similar clinical picture.
Diagnosis reference
1. Orange JS, Ballow M, Stiehm ER, et al: Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 130 (3 Suppl):S1–S24, 2012. doi:10.1016/j.jaci.2012.07.002
Treatment of SADNI
Pneumococcal conjugate vaccine
Sometimes prophylactic antibiotics and sometimes immune globulin replacement therapy
Patients should be vaccinated with the pneumococcal conjugate vaccine.
Rarely, when infections recur frequently despite prophylactic antibiotics, immune globulin replacement therapy can be given.
