immunodeficiencies

Immunodeficiencies are a group of disorders characterized by impaired function or number of immune-system components, resulting in increased susceptibility to infections, poor responses to vaccines, and a tendency toward immune dysregulation such as autoimmunity or inflammation. They encompass inherited conditions and acquired conditions that diminish immune defenses.

They are broadly classified as primary immunodeficiencies, which are inherited and usually present from infancy, and secondary (acquired) immunodeficiencies, which arise from infections (notably HIV), malnutrition, aging, splenectomy, or immunosuppressive therapies. Primary immunodeficiencies can involve defects in humoral immunity (antibodies and B cells), cellular immunity (T cells), phagocytes, or the complement system. Notable examples include severe combined immunodeficiency, X-linked agammaglobulinemia, common variable immunodeficiency, and Wiskott–Aldrich syndrome.

Clinical features include recurrent or unusual infections, infections with opportunistic organisms, failure to thrive in children, and poor responses to vaccines. Diagnosis combines clinical history with laboratory testing such as complete blood count, quantitative immunoglobulins, lymphocyte subsets, functional vaccine responses, and genetic testing when indicated.

Management focuses on preventing infections and supporting immune function. This may involve immunoglobulin replacement therapy for antibody deficiencies, antimicrobial prophylaxis, prompt treatment of infections, and avoidance of certain live vaccines. For some severe primary immunodeficiencies, hematopoietic stem cell transplantation or emerging gene therapies may be appropriate.

Secondary immunodeficiencies are more common and arise from factors such as HIV, malnutrition, cancer chemotherapy, or systemic corticosteroid or biologic therapies. Improved diagnostics, newborn screening for severe combined immunodeficiency in some regions, and advances in targeted therapies are gradually improving outcomes.