immunology allergic disorders
Overview of Immunodeficiency Disorders
Primary Immunodeficiencies
These disorders are genetically determined; they may occur alone or as part of a syndrome. In 2022, the International Union of Immunological Societies reported that 485 inborn errors of immunity have been linked to primary immunodeficiency disorders ( Primary immunodeficiency references ). Despite advances in genetic discoveries, it is thought that only about 20 to 30% of current primary immunodeficiencies have a definable genetic mutation. Primary immunodeficiencies typically manifest during infancy and childhood as abnormally frequent (recurrent) or unusual infections. About 70% of patients are<20 years at onset; because transmission is often X-linked, 60% are male. Overall incidence of symptomatic disease is about 1/280 people. Primary immunodeficiencies are classified by the main component of the immune system that is deficient, absent, or defective: Humoral immunity deficiencies None Cellular immunity deficiencies None Combined humoral and cellular immunity deficiencies None Phagocytic cell defects None Complement deficiencies None As more molecular defects are defined, classifying immunodeficiencies by their molecular defects will become more appropriate ( Primary immunodeficiency references ). are genetically determined immunodeficiencies with immune and nonimmune defects. Nonimmune manifestations are often more easily recognized than those of the immunodeficiency. Examples are Ataxia-Telangiectasia , cartilage-hair hypoplasia, Immunodeficiency typically manifests as recurrent infections. The age at which recurrent infections began provides a clue as to which component of the immune system is affected. Other characteristic findings tentatively suggest a clinical diagnosis (see Characteristic Clinical Findings in Some Primary Immunodeficiency Disorders ). However, tests are needed to confirm a diagnosis of immunodeficiency (see Treatment and Prognosis depend on the specific disorder ( Humoral immunity deficiencies (B-cell defects) that cause antibody deficiencies account for 50 to 60% of primary immunodeficiencies (see table Humoral Immunity Deficiencies ). Serum antibody titers decrease, predisposing to bacterial infections. The most common B-cell disorder is Selective IgA Deficiency None Selective IgA deficiency is the most common B-cell disorder, but many patients are asymptomatic. Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency. For diagnostic evaluation of humoral immunity deficiencies, see Approach to the Patient With Suspected Immunodeficiency and table Cellular immunity deficiencies (T-cell defects) account for about 5 to 10% of primary immunodeficiencies and predispose to infection by viruses, Pneumocystis jirovecii Pneumonia , fungi, other opportunistic organisms, and many common pathogens (see table The most common T-cell disorders are Chronic Mucocutaneous Candidiasis None DiGeorge Syndrome None X-linked Lymphoproliferative Syndrome None ZAP-70 Deficiency None Primary natural killer cell defects, which are very rare, may predispose to viral infections (specifically Overview of Herpesvirus Infections ) and tumors. Secondary natural killer cell defects can occur in patients who have various other primary or secondary immunodeficiencies, frequently in those with cancer or autoimmune disease and in those taking certain medications ( Primary immunodeficiency references ). For diagnostic evaluation of cellular immunity deficiencies, see tablesand. Combined humoral and cellular immunity deficiencies (B- and T-cell defects) account for about 20% of primary immunodeficiencies (see table Combined Humoral and Cellular Immunity Deficiencies ). The most important form is Severe Combined Immunodeficiency (SCID) (SCID) In some forms of combined immunodeficiency (eg, purine nucleoside phosphorylase deficiency), Ig levels are normal or elevated, but because of inadequate T-cell function, antibody formation is impaired. For diagnostic evaluation of combined humoral and cellular immunodeficiencies, see table. Phagocytic cell defects account for 10 to 15% of primary immunodeficiencies; the ability of phagocytic cells (eg, monocytes, macrophages, granulocytes such as neutrophils and eosinophils) to kill pathogens is impaired (see table Phagocytic Cell Defects ). Cutaneous staphylococcal and gram-negative infections are characteristic. The most common (although still rare) phagocytic cell defects are Chédiak-Higashi Syndrome None Chronic Granulomatous Disease (CGD) None Neutropenia caused by intrinsic defects in myeloid cells or their precursors None Leukocyte Adhesion Deficiency (types 1 and 2) For diagnostic evaluation of phagocytic cell defects, see tablesand. 2% of primary immunodeficiencies); they include isolated deficiencies of complement components or inhibitors and may be hereditary or acquired (see table Complement Deficiencies ). Hereditary deficiencies are autosomal recessive except for deficiencies of The most serious consequences are Recurrent infection, which is due to defective opsonization Autoimmune disorders (eg, systemic lupus erythematosus, glomerulonephritis), which are due to defective clearance of antigen-antibody complexes , causes Hereditary and Acquired Angioedema . Complement deficiencies can affect the classical and/or alternate pathways of the Complement System . The alternate pathway shares C3 and C5 through C9 with the classical pathway but has additional components: factor D, factor B, properdin (P), and regulatory factors H and I. For diagnostic evaluation of complement deficiencies, see tablesand. 1.Tangye SG, Al-Herz W, Bousfiha A, et al: Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee [published online ahead of print, 2022 Jun 24].J Clin Immunol2022;1–35. doi:10.1007/s10875-022-01289-3 2.Chinn IK, Chan AY, Chen K, et al: Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma and Immunology.J Allergy Clin Immunol145(1):46–69, 2020. doi: 10.1016/j.jaci.2019.09.009 3.Leonardi L, Rivalta B, Cancrini C, et al: Update in primary immunodeficiencies.Acta Biomed91(11-S):e2020010, 2020. doi: 10.23750/abm.v91i11-S.10314 4.Moon WY, Powis SJ: Does natural killer cell deficiency (NKD) increase the risk of cancer? NKD may increase the risk of some virus induced cancer.Front Immunol10:1703, 2019. Published 2019 Jul 19. doi:10.3389/fimmu.2019.01703 5.Schleinitz N, Vély F, Harlé JR, Vivier E: Natural killer cells in human autoimmune diseases.Immunology131(4):451–458, 2010. doi:10.1111/j.1365-2567.2010.03360.x 