- Immunodeficiency refers to a state in which the immune system’s ability to defend the body against infections, malignancies, and other diseases is impaired. It can be broadly categorized into primary immunodeficiencies, which are congenital and caused by genetic defects, and secondary (or acquired) immunodeficiencies, which develop later in life due to external factors such as infections, malnutrition, chemotherapy, or chronic diseases.
- In both forms, the underlying problem lies in the disruption of normal immune mechanisms, including antibody production, T-cell or B-cell function, complement pathways, or phagocytic activity. Clinically, immunodeficiency is characterized by increased susceptibility to infections, often with unusual pathogens, recurrent or severe illness, and, in some cases, a predisposition to autoimmune disease or malignancy.
- Primary immunodeficiencies (PIDs) represent a diverse group of disorders caused by inherited mutations affecting the development or function of the immune system. These conditions range from relatively mild selective IgA deficiency to life-threatening disorders such as severe combined immunodeficiency (SCID), where both T- and B-cell immunity are profoundly impaired. Other examples include chronic granulomatous disease, Wiskott–Aldrich syndrome, and common variable immunodeficiency (CVID). Advances in molecular genetics and next-generation sequencing have greatly expanded the classification of PIDs, with hundreds of distinct entities now recognized. Early detection is critical, as many of these disorders can be treated with interventions such as hematopoietic stem cell transplantation, enzyme replacement therapy, or gene therapy.
- Secondary immunodeficiencies are far more common and arise from non-genetic causes that weaken immune function. Among the most well-known is HIV/AIDS, where viral infection selectively targets CD4+ T lymphocytes, leading to progressive immune collapse and opportunistic infections. Other causes include immunosuppressive therapies (such as corticosteroids, chemotherapy, and biologics used in cancer or autoimmune diseases), hematological malignancies (like leukemia and lymphoma), metabolic disorders (including diabetes and chronic renal failure), and malnutrition, which is the leading cause of immunodeficiency worldwide. Unlike many primary forms, secondary immunodeficiencies may be reversible if the underlying cause is corrected.
- Diagnosis of immunodeficiency requires careful clinical evaluation, including a history of recurrent, severe, or atypical infections, family history of immune disorders, and laboratory studies. Basic investigations include complete blood counts, measurement of immunoglobulin levels, lymphocyte subsets, and complement activity. Functional assays, genetic testing, and pathogen-specific evaluations may provide further insights. Newborn screening for severe immunodeficiencies, particularly SCID, has been implemented in many countries, allowing life-saving interventions before the onset of infections.
- Treatment strategies for immunodeficiency depend on the type and severity of the disorder. For many antibody deficiencies, immunoglobulin replacement therapy is the cornerstone of management, helping to reduce infection frequency and severity. Patients with profound cellular or combined immunodeficiencies may benefit from bone marrow or stem cell transplantation, which can restore immune competence. Gene therapy is an emerging frontier, showing success in conditions such as adenosine deaminase (ADA)-deficient SCID. Supportive measures, including prophylactic antibiotics, antifungals, or antivirals, are often necessary, particularly in patients with profound immune suppression. In secondary immunodeficiencies, addressing the underlying cause—such as discontinuing immunosuppressive drugs, treating HIV with antiretroviral therapy, or correcting nutritional deficiencies—can restore immune function.
- Beyond infections, immunodeficiencies may also predispose patients to autoimmunity and cancer, reflecting the immune system’s role not only in defense against pathogens but also in immune regulation and tumor surveillance. As such, long-term monitoring and multidisciplinary care are essential. Research in immunodeficiency continues to expand, shedding light not only on rare inherited conditions but also on the fundamental workings of the human immune system. With advances in molecular medicine, gene editing, and targeted immunotherapies, the outlook for patients with immunodeficiency has improved dramatically, transforming conditions once deemed fatal into manageable or even curable diseases.
