Immunodeficiency diseases

  • Used to treat conditions like autoimmune diseases and to prevent transplant rejection.

  • Major classes include corticosteroids, calcineurin inhibitors, and cytotoxic drugs.

  • Adverse effects: Increased risk of infections, malignancies, and organ-specific toxicities.

Types of Immunodeficiencies

  1. T-cell Deficiencies

    • Causes: Abnormalities in T-cell function.

    • Examples:

      • Thymic aplasia (Di George’s syndrome):

        • Features: Defective T cells, recurrent infections, chromosomal deletion at 22q11, cardiac anomalies, hypoplastic thymus, hypocalcemia.

      • Chronic mucocutaneous candidiasis:

        • Features: Deficit in IL-17-producing T cells, severe chronic candidiasis of mucosa, skin, and nails.

  2. B-cell Deficiencies

    • Causes: Low or absent antibody levels, leading to recurrent bacterial infections.

    • Examples:

      • X-linked agammaglobulinemia (Bruton disease):

        • Features: Defect in B-cell development, recurrent bacterial infections, genetic defect in BTK.

      • Selective IgA deficiency:

        • Features: Very low IgA levels, recurrent sinopulmonary infections, autoimmune disorders.

      • Hyper-IgM syndrome:

        • Features: High IgM levels but low IgG, IgA, and IgE, mutation in CD40L gene, severe recurrent bacterial infections.

      • Common variable immunodeficiency:

        • Features: Faulty B-cell differentiation, low immunoglobulin levels, recurrent bacterial infections, chronic lung disease.

  3. Combined T & B Cell Deficiency

    • Causes: Defective or absent B and T cells.

    • Examples:

      • Severe combined immunodeficiency (SCID):

        • Features: Deficiency of both B and T-cell function, recurrent severe infections, mutations in IL2RG gene.

  4. Phagocyte Disorders

    • Examples:

      • Chronic granulomatous disease:

        • Features: Mutations in genes related to NADPH oxidase, defective bactericidal activity.

      • Myeloperoxidase deficiency:

        • Features: Mutations in MPO gene, recurrent Candida infections.

      • Chediak-Higashi syndrome:

        • Features: Mutations in LYST gene, reduced intracellular killing and chemotactic movement.

  5. Complement Deficiencies

    • Causes: Overactivation or deficiency of complement proteins.

    • Examples:

      • Hereditary angioedema: Caused by C1 inhibitor deficiency.

      • Paroxysmal nocturnal hemoglobinuria: Failure of decay-accelerating factor.

      • Deficiencies in C3, C6, C7, or C8: Increased susceptibility to bacterial infections.

Acquired Immunodeficiencies

  • T-Cell Deficiencies:

    • AIDS: Opportunistic infections due to reduced CD4 T-cells from HIV.

    • Measles: Transient suppression of delayed hypersensitivity.

  • B-Cell Deficiencies:

    • Malnutrition: Reduces IgG synthesis.

    • Asplenia: Suppresses antibody responses to new antigens.

  • Complement Deficiencies:

    • Liver failure: Reduces synthesis of complement proteins.

  • Phagocyte Deficiencies:

    • Neutropenia: Severe infections caused by pyogenic bacteria.

    • Common causes: Cytotoxic drugs, leukemia, autoimmune destruction.

  • Other Causes:

    • Corticosteroids: Depletion of CD4 cells, monocytopenia, decreased eosinophils and basophils.

    • Methotrexate: Reduces immunoglobulin synthesis.

    • Cyclosporine: Inhibits T cell signaling and IL 2 dependent signal transduction.

    • Others: Malnutrition, cancers, Cushing's syndrome, aging, and pregnancy.

Thymic aplasia, also known as Di George’s syndrome, which is a congenital condition characterized by:

Specific Deficiency:

  • Defective T cells and suppressed antibody responses.

  • Defective fetal development of the third and fourth pharyngeal arches, which usually form the parathyroid glands, aortic arch, and thymus.

  • Chromosomal deletion at 22q11.

Clinical Features:

  • Recurrent sinopulmonary infections due to severe combined immunodeficiency.

  • Common viral infections include cytomegalovirus, Epstein-Barr virus, JC virus, and varicella-zoster virus.

  • Increased risk of fungal infections such as Candida, Pneumocystis jirovecii, and Cryptococcus.

  • Classic triad in infants: cardiac anomalies, hypoplastic thymus, and hypocalcemia.