Immunodeficiency is a condition where the immune system is compromised, classified into primary (genetic) and secondary (acquired) disorders. Primary immunodeficiencies include various genetic disorders affecting B cells and antibodies, leading to increased susceptibility to infections, while secondary immunodeficiencies can arise from external factors like medications or infections. Treatment options vary, including immunoglobulin replacement, antibiotics, and in severe cases, bone marrow or stem cell transplants.

1. Immunodeficiency
Sumbul Parveen
GM20-115

2. What is Immunodeficiency
- Immunodeficiency is a state in which the ability of immune system is compromised or entirely absent
to fight against infectious diseases and cancer.
- Two types of immunodeficiency disorders:
1. primary or congenital or inherited
2. secondary or acquired
- Immunodeficiency can be specific or non-specific
1. specific = abnormalities of B & T cells
2. non-specific= abnormalities of non specific components

3. Primary immunodeficiency
- Primary B cell immunodeficiency refers to a group of genetic disorders
that affect the body's ability to produce adequate B cells or antibodies.
- These conditions lead to increased susceptibility to infections, particularly
bacterial infections
- usually present at birth and are usually hereditary.
- evident during infancy or childhood. However, some disorders (such as
common variable immunodeficiency) are not recognized until adulthood.

4. Types of primary B cell immunodeficiency
● X-linked Agammaglobulinemia (XLA)
● Common Variable Immunodeficiency (CVID)
● Selective IgA Deficiency
● Hyper-IgM Syndrome
● IgG Subclass Deficiencies
● Transient Hypogammaglobulinemia of Infancy

5. 1. X-Linked Agammaglobulinemia (XLA)
• Cause: Mutation in the BTK(Bruton tyrosine kinase) gene.
• Characteristics: Very low or absent B cells and immunoglobulins. Typically
diagnosed in early childhood.
• Symptoms: Recurrent bacterial infections.
2. Common Variable Immunodeficiency (CVID)
• Cause: Genetic factors (multiple possible genes).
• Characteristics: Low levels of immunoglobulins (IgG, IgA, and/or IgM) with
impaired antibody response.
• Symptoms: Recurrent infections, autoimmune diseases, and increased risk of
lymphoma.

6. 3. Selective IgA Deficiency
• Description: Most common primary immunodeficiency.
• Characteristics: Low levels of IgA while other immunoglobulin levels are normal.
• Symptoms: Increased respiratory and gastrointestinal infections, often
asymptomatic.
4. Hyper-IgM Syndrome
• Cause: Defect in CD40 ligand (usually X-linked) or other genetic mutations.
• Characteristics: Elevated IgM levels with low IgG and IgA.
• Symptoms: Recurrent infections and potential autoimmune issues.

7. 5. IgG Subclass Deficiencies
• Description: Deficiencies in one or more subclasses of IgG (IgG1, IgG2, IgG3, IgG4).
• Characteristics: Varying levels of susceptibility to infections, depending on the specific
subclass affected.
6. Transient Hypogammaglobulinemia of Infancy
• Description: A temporary condition seen in infants.
• Characteristics: Delayed maturation of the immune system leading to low immunoglobulin
levels.
• Symptoms: Increased infections during infancy, usually resolves by age 2-3.

8. Diagnosis
1. Clinical Assessment
• History: Detailed medical history, including frequency and type of infections, family history
of immunodeficiency, and any autoimmune conditions.
• Physical Examination: Look for signs of recurrent infections or other related symptoms.
2. Laboratory Tests
• Immunoglobulin Levels: Measure serum levels of IgG, IgA, and IgM. Low levels can indicate
specific deficiencies.
• B Cell Counts: Flow cytometry is used to assess the number and function of B cells in the
blood.
• Specific Antibody Response: Evaluate the ability to mount an antibody response to
vaccinations (e.g., pneumococcal or tetanus vaccines).

9. 3. Genetic Testing
• Targeted Gene Testing: If a specific primary immunodeficiency is suspected (e.g.,
XLA, Hyper-IgM syndrome), genetic tests can confirm mutations in relevant genes
(e.g., BTK, CD40L).
4. Functional Assays
• B Cell Function Tests: Assess how well B cells can produce antibodies in
response to stimuli.
5. Imaging Studies
• Lymphoid Tissue Assessment: Imaging may be used to evaluate the presence of
lymphoid tissue (e.g., spleen, lymph nodes).

10. Treatment
1. Immunoglobulin Replacement Therapy
• Intravenous Immunoglobulin (IVIG) or Subcutaneous Immunoglobulin (SCIG): These therapies
provide antibodies to help prevent infections in individuals with low immunoglobulin levels.
2. Antibiotic Prophylaxis: co-amoxiclav, doxycycline or azithromycin
• Long-term Antibiotics: Regular antibiotics may be prescribed to prevent recurrent infections,
particularly in young children or those with severe deficiencies.
3. Vaccination: vaccines may be given to enhance protective immunity.
4. Monitoring and Supportive Care for regular follow-ups.
5. Bone Marrow or Stem Cell Transplant( for severe cases)

11. Secondary Immunodeficiency

12. Secondary immunodeficiency (SID) occurs when the immune system is weakened by another
treatment or illness. What causes secondary immunodeficiency? There are many potential causes
of SID but the most common examples are blood or bone marrow disorders, drugs (medicines)
and treatment for cancer.

13. What Are the Causes of Secondary Immunodeficiency Disorders?
Radiation or chemotherapy, which can lead to a secondary immunodeficiency disorder known as neutropenia.
Chronic disease.
Severe burns.
Infections due to human immunodeficiency virus (HIV) can result in acquired immune deficiency syndrome (AIDS)

14. The bone marrow transplant is the most common treatment for secondary immunodeficiency.
Therapies such as the ART (Antiretroviral Therapy) antiviral treatment, allow white blood cells to
recover from a dangerous loss. These drugs have significantly increased the lifespan of people
with HIV and AIDS

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