Humoral Immunodeficiency (B Cell Defects)
المؤلف:
APURBA S. SASTRY , SANDHYA BHAT
المصدر:
Essentials Of Medical Microbiology 2021
الجزء والصفحة:
3rd edition , p208-210
2025-09-24
386
Bruton Disease (X-linked Agammaglobulinemia)
Bruton disease is one of the more common forms of primary immunodeficiency. It is characterized by:
- Failure of pre-B cells to differentiate into immature B cells in the bone marrow—due to absence of an enzyme called Bruton’s tyrosine kinase which is involved in transformation of pre-B cell into immature B cell
- As a result, there occurs total absence of B cells and plasma cells in the circulation, with depressed serum levels of all classes of immunoglobulins. However, Pre-B cells are found in normal numbers in bone marrow and the T cell-mediated responses are also normal
- The B cell maturation stops at pre-B cell stage; after the synthesis of heavy-chain without forming the light chains. Hence the cytoplasm of pre-B cell may have incomplete immunoglobulins
- Bruton’s tyrosine kinase is X-linked; hence, this disease is seen primarily in males; nevertheless, sporadic cases have been described in females
- Secondary infections are seen after 6 months of age, (when maternal antibodies are depleted), such as:
* Recurrent bacterial infections caused by pathogens that are usually cleared by antibody opsonization (e.g. Haemophilus influenzae, Streptococcus pneumoniae, or Staphylococcus aureus) leading to acute and chronic pharyngitis, sinusitis, otitis media, bronchitis, and pneumonia
* Viruses that are cleared by neutralizing antibodies, e.g. enteroviruses
* Parasites which are usually resisted by secretory IgA, e.g. Giardia lamblia.
- Autoimmune diseases (such as SLE and dermatomyositis) also occur in up to 20% of cases.
Common variable Immunodeficiency
This is a heterogeneous group of both sporadic and inherit ed forms of the disease characterized by hypogammaglobulinemia, increased susceptibility to infection, autoimmune disorders (hemolytic anemia, pernicious anemia), as well as lymphoid tumors. The clinical manifestations are superficially similar to those of Bruton diseases; but differ in the following aspects:
- Both sexes are affected equally
- Onset of symptoms is much later, in the second or third decade of life
- It is also B cell development defect; B cells may be present in circulation in normal numbers, but they appear defective in their ability to differentiate into plasma cells and secrete immunoglobulins
- The diagnosis is usually one of exclusion (after other causes of immunodeficiency are ruled out); the basis of the immunoglobulin deficiency is variable (hence the name)
- The defect in the antibody production has been variably attributed to intrinsic B cell defects, deficient T cell helper, or excessive T cell suppressor activity.
Isolated IgA Deficiency
IgA deficiency is the most common of all the primary immunodeficiency diseases, affects about 1 in 700 white individuals.
- In healthy normal individuals, IgA is predominant in mucosal secretions and involves in providing immunity at mucosal sites of intestine and respiratory tract
- Therefore, the weakened mucosal defences due to IgA deficiency predispose patients to recurrent sinopulmonary infections and diarrhea. There is also a significant (but unexplained) association with autoimmune diseases
- Pathogenesis: IgA deficiency occurs due to a block in the terminal differentiation of IgA-secreting B cells to plasma cells, which in turn is due to altered T cell production of cytokines that drive IgA responses (e.g. TGF-β and IL-5) or due to intrinsic B cell defect. The levels of other immunoglobulins are usually normal or even excess.
hyper-IgM Syndrome
Hyper-IgM syndrome is an X-linked disorder; results due to a defect in isotype class switchover of B cells.
- Underlying genetic defect is mutations in either CD40L or CD40 genes, leading to prevention of interaction between T and B cell; thus blocking the class switchover
- A block in class switchover results in lack of synthesis of other classes of antibodies such as IgG, IgA, and IgE with a normal or supernormal levels of IgM
* Deficiency of IgG leads to defect in opsonization and complement activation (predisposes to recurrent pyogenic infections) and IgA deficiency leads to increased recurrent sinopulmonary infections and diarrhea
* Excess IgM antibodies can react with blood cells, resulting in autoimmune hemolytic anemia, thrombocytopenia, or neutropenia.
- Because CD40L signals are involved in macrophage activation and thus producing delayed hypersensitivity response, hence patients with defect in CD40L are more susceptible to Pneumocystis jirovecii infection
- Hyper-IgM syndrome is X-linked in 70% of the cases affecting males; in the remaining patients, the precise mutations have not been fully characterized.
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