(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more ).
Selective antibody deficiency with normal immunoglobulins (SADNI) is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . 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 ). The inheritance and pathophysiology have not been elucidated, but some evidence suggests that the cause may be inherited molecular abnormalities.
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 Atopic Dermatitis (Eczema) Atopic dermatitis is a chronic relapsing inflammatory skin disorder with a complex pathogenesis involving genetic susceptibility, immunologic and epidermal barrier dysfunction, and environmental... read more , asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more ). Severity of the disorder varies.
Young children may have a form of SADNI that resolves spontaneously over time.
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, PCV7, PCV13).
Testing usually involves giving the 23-valent polysaccharide pneumococcal vaccine (PPV), with quantitative measurement of antibody response; most clinicians assess response to 12 to 14 serotypes. Ideally, titers are done by the same laboratory both before and after vaccine administration. Response to each serotype 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 PPV for children age 2 to 5 years is defined as protective antibodies to ≥ 50% of the serotypes tested, with at least a 2-fold increase in the titers; patients 6 to 65 years should have protective antibodies to ≥ 70% of serotypes. Patients with abnormal results can be classified phenotypically as follows (1 Diagnosis reference Selective antibody deficiency with normal immunoglobulins (Ig) is characterized by deficient specific antibody response to polysaccharide antigens but not to protein antigens, despite normal... read more ):
Memory phenotype: Normal initial response to PPV23, 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 serotypes but fewer than the expected number for their age
Severe phenotype: Protective titers to ≤ 2 serotypes, and the titer, if present, tends to be low (< 1.3–2.0 microg/mL [< 1.3–2.0 mg/L]).
Family members of known patients do not need screened unless they manifest a similar clinical picture.
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 (eg, 13-valent) vaccine Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more .
Sinopulmonary infections and atopic manifestations are treated aggressively. Uncommonly, when infections continue to recur, prophylactic antibiotics (eg, amoxicillin, trimethoprim/sulfamethoxazole) can be given.
Rarely, when infections recur frequently despite prophylactic antibiotics, immune globulin Replacement of missing immune components Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more replacement therapy can be given.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Pneumovax 23, Pnu-Imune-23 , Prevnar, Prevnar 13 , Prevnar 20, VAXNEUVANCE|
|Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox|
|Primsol, Proloprim, TRIMPEX|