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Selective Antibody Deficiency With Normal Immunoglobulins (SADNI)


James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Reviewed/Revised Jan 2023
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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.

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).

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.

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

Sinopulmonary infections and atopic manifestations are treated aggressively. Uncommonly, when infections continue to recur, prophylactic antibiotics (eg, amoxicillin, trimethoprim/sulfamethoxazole) can be given.

Drugs Mentioned In This Article

Drug Name Select Trade
Pneumovax 23, Pnu-Imune-23 , Prevnar, Prevnar 13 , Prevnar 20, VAXNEUVANCE
No brand name available
Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox
Primsol, Proloprim, TRIMPEX
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