Overview of Immunodeficiency Disorders

These disorders are genetically determined; they may occur alone or as part of a syndrome. In 2019, the International Union of Immunological Sciences reported that 354 inborn errors of immunity and 430 genes have been linked to primary immunodeficiency disorders ( 1 Primary immunodeficiency references Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more ).The molecular basis for about 80% is known.

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:

As more molecular defects are defined, classifying immunodeficiencies by their molecular defects will become more appropriate ( 2 Primary immunodeficiency references Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more ).

Primary immunodeficiency syndromes 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 Ataxia-Telangiectasia Ataxia-telangiectasia results from a DNA repair defect that frequently results in humoral and cellular deficiency; it causes progressive cerebellar ataxia, oculocutaneous telangiectasias, and... read more , cartilage-hair hypoplasia, DiGeorge syndrome DiGeorge Syndrome DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell immunodeficiency and hypoparathyroidism. Infants with DiGeorge syndrome have low-set ears, midline facial... read more , hyper-IgE syndrome Hyper-IgE Syndrome Hyper-IgE syndrome is a hereditary combined B- and T-cell immunodeficiency characterized by recurrent staphylococcal abscesses of the skin, sinopulmonary infections, and severe pruritic eosinophilic... read more , and Wiskott-Aldrich syndrome Wiskott-Aldrich Syndrome Wiskott-Aldrich syndrome results from a combined B- and T-cell defect and is characterized by recurrent infection, eczema, and thrombocytopenia. (See also Overview of Immunodeficiency Disorders... read more . Despite the presence of immunodeficiencies, some patients also develop autoimmune disorders Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following hypersensitivity reactions may be involved: Type II: Antibody-coated cells... read more .

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 Characteristic Clinical Findings in Some Primary Immunodeficiency Disorders ). However, tests are needed to confirm a diagnosis of immunodeficiency (see Initial and Additional Laboratory Tests for Immunodeficiency Initial and Additional Laboratory Tests for Immunodeficiency ). If clinical findings or initial tests suggest a specific disorder of immune cell or complement function, additional tests Additional testing Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more are indicated (see Specific and Advanced Laboratory Tests for Immunodeficiency Specific and Advanced Laboratory Tests for Immunodeficiency* ).

Treatment and prognosis of primary immunodeficiency disorders Prognosis Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more depend on the specific disorder ( 3 Primary immunodeficiency references Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more ).

Causes (see table Causes of Secondary Immunodeficiency Causes of Secondary Immunodeficiency ) include

Secondary immunodeficiency also occurs among critically ill, older, or hospitalized patients. Prolonged serious illness may impair immune responses; impairment is often reversible if the underlying illness resolves.

Immunodeficiency can result from loss of serum proteins (particularly IgG and albumin) through the following:

Enteropathy may also lead to lymphocyte loss, resulting in lymphopenia.

Treatment focuses on the underlying disorder; for example, a diet high in medium-chain triglycerides may decrease loss of immunoglobulins (Igs) and lymphocytes from the gastrointestinal tract and be remarkably beneficial.

If a specific secondary immunodeficiency disorder is suspected clinically, testing should focus on that disorder (eg, diabetes, HIV infection, cystic fibrosis, primary ciliary dyskinesia).

Some decrease in immunity occurs with aging. For example, in older adults, the thymus tends to produce fewer naive T cells; thus, fewer T cells are available to respond to new antigens. The total number of T cells does not decrease (because of oligoclonality), but these cells can recognize only a limited number of antigens.

Signal transduction (transmission of antigen-binding signal across the cell membrane into the cell) is impaired, making T cells less likely to respond to antigens. Also, helper T cells may be less likely to signal B cells to produce antibodies.

The number of neutrophils does not decrease, but these cells become less effective in phagocytosis and microbicidal action.

Undernutrition, common among older adults, impairs immune responses. Calcium, zinc, and vitamin E are particularly important to immunity. Risk of calcium deficiency is increased in older adults, partly because with aging, the intestine becomes less able to absorb calcium. Also, the elderly may not ingest enough calcium in their diet. Zinc deficiency is very common among adults living in institutional settings and homebound patients.

Certain disorders (eg, diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more , undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more ), which are more common among older adults, and certain therapies (eg, immunosuppressants, immunomodulatory drugs and treatments), which the elderly are more likely to use, can also impair immunity.