Antibody Deficiency Syndromes

Key Features

Essentials of Diagnosis

• Recurrent bacterial infections, typically due to encapsulated pyogenic bacteria

• Low immunoglobulin levels

• Inability to make specific antibodies to vaccine antigens or infections

General Considerations

• Can be either congenital or acquired

• Defined as hypogammaglobulinemia with low levels of one or more of the immunoglobulins: IgM, IgG, and IgA

• As a group, antibody deficiencies represent nearly half of all primary immunodeficiency diseases that can be classified into

  • Defects of B-cell development

  • Defects in Ig class switching

  • Functional B-cell deficiency

Symptoms and Signs

• Defects in B-cell development

  • Patients are generally immunologically normal with the exception of a severe reduction of B cells in the blood and infections that result from their absence

  • Patients with early defects

    • Have little detectable lymphoid tissue

    • May lack tonsils or palpable lymph nodes

  • Patients with later defects may have palpable lymphoid tissue

  • In both groups, size of spleen is generally normal

• Defects in class switching

  • Presents with various associated features depending on the genetic cause

  • Patients with defects in CD40L and CD40 can have

    • Risk of associated opportunistic infection with Pneumocystis and Cryptosporidium

    • Hypoplastic lymphoid tissue

  • Patients with defective activation-induced cytidine deaminase (AICDA) can have associated autoimmunity, including

    • Idiopathic (or immune) thrombocytopenic purpura (ITP)

    • Hemolytic anemia

    • Autoimmune hepatitis

    • Inflammatory bowel disease

    • Arthritis

    • Interstitial lung disease

  • Both AICDA and uracil DNA N-glycosylase (UNG) deficient patients suffer from lymphoid hyperplasia

• Transient hypogammaglobulinemia

  • Represents a delay in the onset of immunoglobulin synthesis that results in a prolonged nadir

  • Symptomatic patients have recurrent infections, including upper respiratory tract infections, otitis, and sinusitis

• Common variable immunodeficiency (CVID)

  • Patients have recurrent infections, most often of the sinopulmonary tract, but chronic gastrointestinal infections may manifest with recurrent diarrhea

  • Patients are at risk for

    • Bronchiectasis

    • Autoimmune diseases (ITP, autoimmune hemolytic anemia, rheumatoid arthritis, and inflammatory bowel disease)

    • Malignancies (especially gastric carcinoma and lymphoma)

  • Isolated IgA deficiency

    • Most patients are asymptomatic

    • However, can be associated with

      • Inflammatory bowel disease

      • Allergic disease

      • Asthma

      • Autoimmune disorders (thyroiditis, arthritis, vitiligo, thrombocytopenia, and diabetes)

Differential Diagnosis

• Secondary causes of decreased amount of immunoglobulin in the peripheral blood

  • Certain medications

  • Protein-losing states

  • Malnutrition

  • Autoimmune conditions

Diagnosis

Laboratory Findings

• Characteristic feature of antibody deficiency is the absence or severe deficiency of one of the three predominant immunoglobulins found in blood, IgG, IgA, or IgM

  • All three immunoglobulin isotypes are severely reduced in early B-cell development defects; although, IgG deficiency is rarely seen in children younger than 4 months due to the presence of placentally transferred maternal IgG

  • In class switching defects, IgM production can be normal or elevated, whereas production of IgG and IgA is deficient

  • In functional B-cell deficiencies, a combination of antibody production abnormalities may be detected

Treatment

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