, Inhibition; B, B lymphocyte; T, T lymphocyte. (Adapted from Abbas AK, Lichtman AH, Pober JS: Cellular and Molecular Immunology, ed 3, Philadelphia, 1997, Saunders.)
The gene defects leading to the majority of cases of CVID decreased while total IgG levels are normal. Normal indiare unknown. Some patients have a defect in the gene encod-viduals can express low levels of one or more subclasses, so ing for inducible co-stimulator (ICOS) on activated T cells, a history of recurrent infections is important. An inability to transmembrane activator and calcium-modulating cyclophi-synthesize specific antibody titers to protein or polysaccharide lin ligand interactor (TACI), CD19, CD21, CD81, or BAFF-R. antigens is the best marker of IgG subclass deficiency associ-It is important to exclude X-linked agammaglobulinemia, ated with recurrent infections and requiring therapy. X-linked lymphoproliferative disease, or hyper-IgM syndrome Transient hypogammaglobulinemia of infancy is a temas well as other causes of hypogammaglobulinemia, such as porary condition characterized by delayed immunoglobulin hypogammaglobulinemia associated with thymoma, second-production. The pathogenesis of this disorder is unknown ary to protein losing enteropathy, or secondary to medica-but is thought to result from a prolongation of the physiologic tions, before making the diagnosis of CVID. hypogammaglobulinemia of infancy. The immunoglobulin
Selective IgA deficiency is defined as serum IgA levels less nadir at 6 months of age is accentuated, with immunoglobuthan 10 mg/dL with normal levels of other immunoglobulins. lin levels less than 200 mg/dL. Immunoglobulin levels remain The diagnosis cannot be confirmed until the patient is at least 4 diminished throughout the first year of life and usually increase years of age when IgA levels should reach adult levels. Selective to normal, age-appropriate levels, generally by 2 to 4 years of IgA deficiency occurs in approximately 1 in 500 individuals. age. The incidence of sinopulmonary infection is increased in Most patients with selective IgA deficiency are asymptomatic. some patients. The diagnosis is supported by normal levels of In others it is associated with recurrent sinopulmonary infec-both B and T cells and by normal antibody responses to protions, IgG2 subclass deficiency, specific antibody deficiency, tein antigens such as diphtheria and tetanus toxoids. The tranfood allergy, autoimmune disease, or celiac disease. IgA defi-sient nature of this disorder cannot be confirmed, however, ciency occurs in families, suggesting autosomal inheritance. until immunoglobulin levels return to normal ranges.
IgG subclass deficiency occurs when the level of antibod-Specific antibody deficiency syndrome is characterized by ies in one or more of the four IgG subclasses is selectively recurrent infections with normal immunoglobulin levels and
Agammaglobulinemia X-linked, AR Infancy (6–9 Recurrent infections, Arrest in B-cell Lymphoid hypoplasia mo) sinusitis, pneumonia, differentiation (pre-B level); meningitis (encapsulated mutations in: Btk gene bacteria, enteroviruses) (X-linked); μ chain, BLNK, Igα, Igβ, Vpre-B, and λ5 (AR)
Hyper-IgM syndrome AR Variable Sinopulmonary infections Defect in AID, UNG Autoimmunity
AD, Autosomal dominant; AID, activation-induced cytidine deaminase; AR, autosomal recessive; ITP, idiopathic thrombocytopenic purpura; RA, rheumatoid arthritis;