Hypogammaglobulinemia

Hypogammaglobulinemia refers to a group of immunodeficiencies characterized by low levels of immunoglobulins (Ig), or antibodies. Immunodeficiencies can be classified according to the cell of the immune system that is defective, like B- and T-cell disorders, which respectively lead to a deficiency in antibody-mediated and cell-mediated immune responses. 

Hypogammaglobulinemias are classified into primary and secondary depending on the underlying cause. Primary hypogammaglobulinemias are inherited disorders caused by genetic mutations or chromosomal abnormalities often with an unknown underlying cause. In adults, the two most common forms of primary hypogammaglobulinemia are common variable immune deficiency (CVID) and selective IgA deficiency. In children, a common form is X-linked agammaglobulinemia, which is caused by a mutation in the BTK gene (which is located on the X chromosome). Finally, there is severe combined immunodeficiency (SCID), a severe form of primary immunodeficiency caused by a genetic mutation that affects the development and function of immune cells. With SCID, the immune system is so dysfunctional that it is considered almost completely absent as there is a lack of both antibody-mediated and cell-mediated immune responses.

Signs and symptoms of hypogammaglobulinemia include an increased tendency to develop recurrent infections that are typically caused by encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Pseudomonas aeruginosa). Most often, these bacterial infections affect the respiratory tract, causing recurrent sinusitis, otitis media, pharyngitis, bronchitis, and pneumonia. Over time, if lung infections are not properly treated, they can lead to the development of bronchiectasis, which is when the bronchi become abnormally enlarged due to chronic inflammation. In addition, individuals may also develop viral gastrointestinal infections as well as infections from intestinal parasites, like giardia lamblia.

Treatment of hypogammaglobulinemia depends on the underlying cause. For primary disorders, treatment often involves immunoglobulin replacement therapy with lifelong monthly IVIG infusions. Intravenous immunoglobulin (IVIG) is a concentrate of pooled immunoglobulins from healthy donors that provides a diverse set of antibodies, which gives people with hypogammaglobulinemia passive immunity to help boost their immune system. In addition, individuals with associated autoimmune conditions may require immunosuppressive therapy with corticosteroids and immunomodulators. The recurrent bacterial infections experienced by individuals with hypogammaglobulinemia can be treated with antibiotics.

Treatment of secondary hypogammaglobulinemias depends on the underlying cause. However, treating the specific cause is rarely possible; therefore, supportive measures are generally necessary. Supportive treatment may include prophylactic vaccination with non-live vaccines and preventive antibiotic therapy in individuals undergoing chemotherapy or other immunocompromising treatments. It’s important to note, all individuals with hypogammaglobulinemia should avoid live attenuated vaccines because the lack of antibodies can make the weakened pathogen difficult to destroy and could lead to potentially life-threatening infections. 

Finally, in severe cases of immunodeficiency, like those with severe combined immunodeficiency (SCID), treatment may involve hematopoietic stem cell transplantation as well as antimicrobial prophylaxis and isolation to prevent catching an infection.