Immunodeficiency Disorders
Immunodeficiency disorders are a group of conditions characterized by impaired or absent function of the immune system, resulting in increased susceptibility to infections, autoimmune phenomena, and, in some cases, malignancies. The pathogenesis of immunodeficiency may involve defects in the development, function, or regulation of immune components such as B cells, T cells, natural killer cells, phagocytes, or the complement system. These defects can be primary, due to genetic mutations affecting immune cell development or signaling, or secondary, resulting from external factors such as infections (e.g., HIV), malignancies, malnutrition, or immunosuppressive therapies. The health impact of immunodeficiency disorders is profound, as affected individuals experience recurrent, severe, or unusual infections, failure to thrive in children, increased risk of autoimmune diseases, and a predisposition to certain cancers. Early recognition and management are critical to prevent morbidity and mortality associated with these disorders.
Primary immunodeficiency disorders are a heterogeneous group of inherited conditions caused by genetic defects that impair the development or function of the immune system. Over 400 distinct PIDs have been identified, including antibody deficiencies (such as X-linked agammaglobulinemia and common variable immunodeficiency), combined immunodeficiencies (e.g., severe combined immunodeficiency), phagocytic defects (e.g., chronic granulomatous disease), and complement deficiencies. Clinical presentation varies depending on the specific defect but generally includes recurrent infections, poor response to vaccines, and in some cases, autoimmune manifestations or lymphoproliferative disorders.
Secondary immunodeficiency disorders arise from external factors that compromise immune function in individuals with previously normal immunity. Common causes include human immunodeficiency virus (HIV) infection, malignancies (particularly hematologic cancers), malnutrition, chronic diseases (such as diabetes or renal failure), and immunosuppressive therapies (e.g., corticosteroids, chemotherapy, or biologic agents). The severity and spectrum of immunodeficiency depend on the underlying cause and may be reversible if the precipitating factor is addressed. Clinically, patients may present with recurrent or severe infections, opportunistic pathogens, and increased susceptibility to certain cancers.
Combined immunodeficiencies involve defects in both humoral (B cell-mediated) and cellular (T cell-mediated) immunity. These disorders, such as severe combined immunodeficiency (SCID), are often severe and present early in life with life-threatening infections, failure to thrive, and poor response to vaccines. Without prompt diagnosis and intervention, such as hematopoietic stem cell transplantation, affected individuals may not survive infancy.
Antibody immunodeficiencies are characterized by impaired production or function of immunoglobulins, resulting in defective humoral immunity. Examples include X-linked agammaglobulinemia, common variable immunodeficiency, and selective IgA deficiency. Patients typically present with recurrent bacterial infections, especially of the respiratory and gastrointestinal tracts, due to the inability to mount effective antibody responses.
Phagocytic cell deficiencies are disorders that impair the ability of neutrophils or macrophages to ingest and destroy pathogens. Chronic granulomatous disease and leukocyte adhesion deficiency are notable examples. Clinical manifestations include recurrent bacterial and fungal infections, poor wound healing, and in some cases, granuloma formation.
Complement deficiencies involve defects in the proteins of the complement system, which play a crucial role in innate immune defense and inflammation. Deficiencies may predispose to recurrent infections with encapsulated bacteria, autoimmune diseases, and, in some cases, angioedema (as seen in hereditary angioedema due to C1 inhibitor deficiency).
The epidemiology of immunodeficiency disorders varies according to type. Primary immunodeficiency disorders collectively have an estimated prevalence of approximately 1 in 1,200 to 2,000 live births, though individual disorders range from extremely rare to relatively common (e.g., selective IgA deficiency may occur in 1 in 300 to 1 in 1,000 individuals, depending on the population). Many PIDs are underdiagnosed due to variable clinical presentations and lack of awareness. Secondary immunodeficiencies are far more prevalent, with HIV/AIDS representing the most globally significant acquired immunodeficiency, affecting over 38 million people worldwide as of 2022. Other causes of secondary immunodeficiency, such as cancer and immunosuppressive therapies, are increasingly common due to advances in medical treatments and aging populations. Both primary and secondary immunodeficiencies affect all age groups, though primary forms often present in childhood, while secondary forms are more common in adults.
Diagnosis of immunodeficiency disorders requires a thorough clinical evaluation, including detailed personal and family history, physical examination, and targeted laboratory investigations. Key clinical clues include recurrent, severe, or unusual infections, poor response to standard therapies or vaccines, failure to thrive, and a family history of immunodeficiency or early childhood deaths. Initial laboratory evaluation typically includes a complete blood count with differential, quantitative immunoglobulin levels (IgG, IgA, IgM), and assessment of vaccine-specific antibody responses. Further testing may involve lymphocyte subset analysis by flow cytometry, assessment of T and B cell function, neutrophil function assays (e.g., oxidative burst), and complement activity tests (CH50, AH50). Genetic testing is increasingly used to confirm specific primary immunodeficiency diagnoses. In secondary immunodeficiencies, investigations are directed toward identifying underlying causes such as HIV testing, malignancy screening, and assessment of nutritional status or medication history. Diagnostic criteria are based on clinical features, laboratory findings, and, where available, genetic confirmation. Early and accurate diagnosis is essential for appropriate management and improved outcomes.
Treatment options for immunodeficiency disorders include several immune globulin preparations and related agents. Immune globulin subcutaneous human-klhw is administered via the subcutaneous route to provide passive immunity and reduce the frequency and severity of infections in patients with antibody deficiencies. Immune globulin subcutaneous (human) and immune globulin subcutaneous [human] are similarly used for subcutaneous replacement therapy, offering the advantage of home administration and steady immunoglobulin levels. Human normal immunoglobulin is utilized to supplement deficient immunoglobulin levels in affected individuals, thereby enhancing humoral immune response. Immune globulin intravenous and immune globulin intravenous (human) are administered intravenously for rapid and effective immunoglobulin replacement, particularly in patients with severe antibody deficiencies or those requiring high-dose therapy for immune modulation. Immunoglobulin intravenous (human); immunoglobulin, normal (human) (Prop INN) is another intravenous formulation indicated for immunoglobulin replacement in various immunodeficiency states. The agent glutathione disulfide; oxiglutatione sodium is included as a therapeutic option and may play a role in supporting antioxidant defenses in immunodeficient patients. Additionally, immunoglobulin intravenous (human); immunoglobulin, normal (human) (Prop INN); TAK-339 is available for intravenous administration to restore immune function in individuals with compromised humoral immunity.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| immune globulin subcutaneous human-klhw | ||||
| immune globulin subcutaneous (human) | ||||
| human normal immunoglobulin | ||||
| immune globulin intravenous | ||||
| immune globulin intravenous (human) | ||||
| immune globulin subcutaneous [human] | ||||
| immunoglobulin intravenous (human); immunoglobulin, normal (human) (Prop INN) | ||||
 | glutathione disulfide; oxiglutatione sodium | 103239-24-3 | C20 H30 N6 O12 S2 . 2 Na | 656.595 |
| immunoglobulin intravenous (human); immunoglobulin, normal (human) (Prop INN); TAK-339 |
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