Primary immunodeficiency diseases affecting adaptive immunity (combined T- and B-cell immune deficiency, B- and T - cell immune deficiency).
Primary immunodeficiency diseases (PIDs) are inherited defects of the immune system, leading to increased susceptibility to infections, autoimmunity, and certain cancers.
Adaptive immunity involves B cells (humoral immunity) and T cells (cell-mediated immunity).
Predominantly B-cell (humoral) deficiencies
X-linked (Bruton) agammaglobulinemia
- Etiology: Mutation in BTK gene → failure of B cell maturation.
- Pathogenesis:
- Absence of mature B cells → severe reduction of all immunoglobulin isotypes.
- Clinical features:
- Recurrent bacterial infections after 6 months (loss of maternal IgG).
- Particularly sinopulmonary infections (e.g., otitis media, pneumonia).
- Treatment: IVIG replacement.
Selective IgA deficiency
- Most common primary immunodeficiency.
- Pathogenesis:
- Defective IgA production → mucosal immunity compromised.
- Clinical features:
- Often asymptomatic.
- Recurrent sinopulmonary and gastrointestinal infections.
- Increased risk of autoimmune diseases, allergies, and anaphylactic reactions to blood products containing IgA.
- Treatment: Supportive.
Common variable immunodeficiency (CVID)
- Etiology: Heterogeneous; often sporadic.
- Pathogenesis:
- Impaired B cell differentiation → decreased IgG, IgA ± IgM.
- Clinical features:
- Recurrent sinopulmonary infections.
- Autoimmune disorders.
- Increased risk of lymphoma and gastric cancer.
- Treatment: IVIG.
3 Predominantly T-cell (cellular) deficiencies
DiGeorge Syndrome (22q11 deletion)
- Etiology: Deletion in 22q11 → defective development of third and fourth pharyngeal pouches.
- Pathogenesis:
- Hypoplasia or absence of thymus → T-cell deficiency.
- Hypoplasia of parathyroids → hypocalcemia.
- Clinical features:
- Recurrent viral and fungal infections.
- Tetany (hypocalcemia).
- Congenital heart defects ( conotruncal anomalies).
- Treatment: Thymic transplant in severe cases, calcium supplementation.