Immunodeficiency

Pathophysiology

Immunodeficiencies (IDs) refer to a category of diseases caused by a weakened immune system, which heightens the likelihood of infections, lymphoproliferation, lymphomas, and various other cancers for those affected by IDs.

IDs can be classified into the following categories:

Primary immunodeficiency disease (PID) typically stems from genetic factors and can be observed in multiple members of the same family. Most patients show mutations in genes crucial for the development of immunological tolerance.

Secondary immunodeficiency disease (SID), on the other hand, involves the weakening of the immune system due to external factors such as aging, the use of immunosuppressive medications, and human immunodeficiency virus (HIV) infection.

Symptoms

Common early symptoms of IDs may include disproportionately severe, persistent, unusual or recurrent (SPUR) infections. Other warning signs for IDs (especially for children) also include:

Experiencing the following infections within 1 year:
- More than 8 ear infections
- 2 or more severe sinus infections
- 2 or more episodes of pneumonia
Experiencing 2 or more systemic infections
Persistent thrush in the mouth
Persistent fungal infection of the skin
Recurrent skin or organ abscesses
Requiring intravenous antibiotics for treating infections
Exhibiting a poor response to antibiotics after 2 or more months of treatment
Inability to gain weight or growth normally
Presence of a family history of PID

Diagnosis

To confirm a diagnosis of immunodeficiencies (IDs), physicians may conduct the following tests: Examine the family history for PID
Complete blood count
Assessment of serum immunoglobulin levels
Assessment of liver and kidney function
Bone marrow aspiration and biopsy
Vaccine challenges

Treatment

To ensure optimal clinical and quality-of-life outcomes for patients with IDs, treatment regimens should be individualized and tailored to meet each patient's specific needs and circumstances. Immunoglobulin (Ig) replacement therapy is a typical treatment approach for IDs, with around 50%-75% of patients with PID requiring this method to replenish their antibody levels. In these therapies, therapeutic immunoglobulin G (IgG) is acquired from healthy donors and administered to patients either intravenously (IVIg) or subcutaneously (SCIg). The goal of Ig replacement therapy is to maintain normal levels of functional serum IgG and sufficient amounts of passive antibodies for the defense against infectious pathogens, thereby minimizing the risk of infections.

The differences between the 2 delivery methods for Ig replacement therapy are as below:

	Intravenous (IVIg)	Subcutaneous (SCIg)
Infusion site	Therapeutic IgG is infused into the vein	Therapeutic IgG is infused into the subcutaneous layer of the abdomen, thighs, or outer buttocks
Route and timing	Administered every 3-4 weeks, with each session lasting for 2-4 hours Need to be administered by a healthcare professional	Administered every 1-2 weeks, with each session lasting for 1-1.5 hours Can be given by self-administration
Changes in IgG levels after infusion	For IVIg, the serum IgG level is elevated initially after infusion, then reduced gradually. Subsequent infusions should be performed before the serum IgG level reaches below a certain level	Due to a slower rate of absorption, SCIg requires a more frequent dosing regimen to maintain a steady level of IgG in the bloodstream

Changes in immunoglobulin levels after intravenous or subcutaneous administration

Patients should consult with their physicians regarding the choice between IVIg and SCIg. Additionally, supportive treatments such as appropriate vaccinations, antibiotics, antifungal, and antiviral prophylactic medications may also be considered.