PIDD

PIDD, short for primary immunodeficiency diseases, refers to a broad group of congenital disorders caused by defects in the immune system. These defects can affect humoral immunity (antibody production), cellular immunity (T cells), phagocytes, complement pathways, or immune regulation. The result is increased susceptibility to infections, as well as potential autoimmune, autoinflammatory, or atopic complications. PIDDs are typically present from birth or early childhood, though some forms are diagnosed in adolescence or adulthood.

Classification and examples

PIDDs are commonly grouped by the part of the immune system that is affected. Major categories include antibody deficiencies (such as X-linked agammaglobulinemia and common variable immunodeficiency), combined immunodeficiencies affecting both B and T cells (severe combined immunodeficiency), phagocytic disorders (for example, chronic granulomatous disease), and various complement deficiencies or immune dysregulation syndromes. Newer genetic and pathway-based classifications continue to refine these categories as more genes are identified.

Diagnosis

Diagnosis is based on clinical history and targeted laboratory testing. Key indicators include recurrent, unusually severe, or atypical infections; growth concerns; and positive family history. Investigations typically involve quantitative immunoglobulin levels, assessment of specific antibody responses to vaccines, lymphocyte subsets by flow cytometry, neutrophil function tests, complement studies, and genetic testing. In some regions, newborn screening using T-cell receptor excision circles (TREC) helps detect T-cell deficiencies early.

Treatment and management

Management is tailored to the specific defect. Antibody deficiencies often require immunoglobulin replacement therapy. Infections are treated promptly with appropriate antimicrobials, and prophylactic antibiotics may be used. Vaccination planning is important: inactivated vaccines are generally safer, while live vaccines are often avoided in severe forms. Some PIDDs are candidates for hematopoietic stem cell transplantation or emerging gene therapies. Multidisciplinary care and regular monitoring are essential.

Prognosis and burden

PIDDs are rare but collectively represent a significant clinical burden due to infection risk and potential complications. Outcomes improve with early recognition, precise diagnosis, and appropriate treatment.