Chapter 50: Primary Immunodeficiency Syndrome

INTRODUCTION

• Primary immune deficiency diseases (PIDDs) are characterized by increased susceptibility to infections and result from the failure of either the humoral or cellular arms of the immune system or both.

• The clinical features of PIDDs are listed in Table 50–1.

  — PIDDs are characterized by recurrent pyogenic bacterial infections, including sinusitis, furunculosis, and recurrent or chronic pneumonias that often terminate in bronchiectasis. These infections are initially responsive to antibiotics but soon recur.

• Evaluation of serum immunoglobulin (Ig) levels and specific antibody responses in patients with recurring infections without an apparent predisposing cause should be made.

  — Baseline Ig levels are often low or virtually absent.

  — Antibody response to immunization is often inadequate.

• Abnormality of cellular immunity causes:

  — Susceptibility to viral, protozoal, and fungal infections may occur.

  — Patients are often anergic. Rejection or clearance of allogeneic cells may be impaired.

  — There may be a secondary defect in humoral immunity because of T-cell dysfunction and loss of B-cell helper activity.

• Autoimmune diseases such as immune-mediated hemolytic anemia, thrombocytopenia, or rheumatoid arthritis-like conditions occur at a higher frequency in certain primary immunodeficiency states.

• The more severe primary immune deficiencies are usually present in infancy, although common variable immunodeficiency (CVID) often presents later in life.

• In Ig-deficient patients, treatment with intravenous immunoglobulin (IVIG) may decrease infectious events.

• The autosomal recessive syndromes are frequently the result of consanguineous marriages.

PREDOMINANT ANTIBODY DEFICIENCIES

X-Linked and Autosomal Recessive Agammaglobulinemia

Definition and Genetic Features

• This deficiency is caused by a maturation defect in B-cell development.

• X-linked agammaglobulinemia is the result of a mutation in the Bruton tyrosine kinase (BTK) gene.

• Autosomal recessive agammaglobulinemia is the result of mutations in genes relevant to immunoglobulin heavy or light chains (ie, IGHM, IGLL1, CD79a, CD79b or the B-cell adaptor molecule, BLINK).

Clinical Features

• X-linked and autosomal recessive agammaglobulinemia have similar clinical features: low Ig levels, decreased B cells, and recurrent infections.

• Normal levels of IgG at birth occur as a result of transfer from maternal circulation. Thus, affected individuals are usually asymptomatic for the ...