Immunodeficiency

Immune deficiency
Classification and external resources
Specialty
ICD-10	D84.9
ICD-9-CM	279.3
DiseasesDB	21506
Patient UK	Immunodeficiency
MeSH	D007153

Immunodeficiency (or immune deficiency) is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired ("secondary") but some people are born with defects in their immune system, or primary immunodeficiency. Transplant patients take medications to suppress their immune system as an anti-rejection measure, as do some patients suffering from an over-active immune system. A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised person may be particularly vulnerable to opportunistic infections, in addition to normal infections that could affect everyone.

Types

By affected component

• Humoral immune deficiency, with signs or symptoms depending on the cause, but generally include signs of hypogammaglobulinemia (decrease of one or more types of antibodies) with presentations including repeated mild respiratory infections, and/or agammaglobulinemia (lack of all or most antibody production) which results in frequent severe infections and is often fatal.
• T cell deficiency, often causes secondary disorders such as acquired immune deficiency syndrome (AIDS).
• Granulocyte deficiency, including decreased numbers of granulocytes (called as granulocytopenia or, if absent, agranulocytosis) such as of neutrophil granulocytes (termed neutropenia). Granulocyte deficiencies also include decreased function of individual granulocytes, such as in chronic granulomatous disease.
• Asplenia, where there is no function of the spleen
• Complement deficiency is where the function of the complement system is deficient

In reality, immunodeficiency often affects multiple components, with notable examples including severe combined immunodeficiency (which is primary) and acquired immune deficiency syndrome (which is secondary).

Comparison of immunodeficiencies by affected component

	Affected components	Main causes	Main pathogens of resultant infections
Humoral immune deficiency	B cells, plasma cells or antibodies	Primary humoral Multiple myeloma Chronic lymphoid leukemia AIDS	Streptococcus pneumoniae Hemophilus influenzae Pneumocystis jirovecii Giardia intestinalis Cryptosporidium parvum
T cell deficiency	T cells	Marrow and other transplantation AIDS Cancer chemotherapy Lymphoma Glucocorticoid therapy	Intracellular pathogens, including Herpes simplex virus, Mycobacterium, Listeria, and intracellular fungal infections.
Neutropenia	Neutrophil granulocytes	Chemotherapy Bone marrow transplantation Dysfunction, such as chronic granulomatous disease	Enterobacteriaceae Oral Streptococci Pseudomonas aeruginosa Enterococcus species Candida species Aspergillus species
Asplenia	Spleen	Splenectomy Trauma Sickle-cell anemia	Polysaccharide encapsulated bacteria, particularly: Streptococcus pneumoniae Haemophilus influenzae Neisseria meningitidis Plasmodium species Babesia species
Complement deficiency	Complement system	Congenital deficiencies	Neisseria species Streptococcus pneumoniae

Primary or secondary

Distinction between primary versus secondary immunodeficiencies are based on, respectively, whether the cause originates in the immune system itself or is, in turn, due to insufficiency of a supporting component of it or an external decreasing factor of it.

Primary immunodeficiency

Main article: Primary immunodeficiency

A number of rare diseases feature a heightened susceptibility to infections from childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies. Many of these disorders are hereditary and are autosomal recessive or X-linked. There are over 80 recognised primary immunodeficiency syndromes; they are generally grouped by the part of the immune system that is malfunctioning, such as lymphocytes or granulocytes.

The treatment of primary immunodeficiencies depends on the nature of the defect, and may involve antibody infusions, long-term antibiotics and (in some cases) stem cell transplantation.

Secondary immunodeficiencies

Further information: Immunosuppression

Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example, malnutrition, aging and particular medications (e.g. chemotherapy, disease-modifying antirheumatic drugs, immunosuppressive drugs after organ transplants, glucocorticoids). For medications, the term immunosuppression generally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the term immunodeficiency generally refers solely to the adverse effect of increased risk for infection.

Many specific diseases directly or indirectly cause immunosuppression. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). HIV directly infects a small number of T helper cells, and also impairs other immune system responses indirectly.

Immunodeficiency and autoimmunity

There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation.

One example is common variable immunodeficiency (CVID) where multiple autoimmune diseases are seen, e.g. inflammatory bowel disease, autoimmune thrombocytopenia and autoimmune thyroid disease. Familial hemophagocytic lymphohistiocytosis, an autosomal recessive primary immunodeficiency, is another example. Pancytopenia, rashes, lymphadenopathy and hepatosplenomegaly are commonly seen in these patients. Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes are also seen in X-linked agammaglobulinemia (XLA). Recurrent bacterial and fungal infections and chronic inflammation of the gut and lungs are seen in chronic granulomatous disease (CGD) as well. CGD is caused by a decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils. Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder that is commonly seen in patients with granulomatosis with polyangiitis (Wegner’s disease) and NK/T cell lymphomas. Wiskott-Aldrich syndrome (WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma. In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) also autoimmunity and infections coexist: organ-specific autoimmune manifestations (e.g. hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis. Finally, IgA deficiency is also sometimes associated with the development of autoimmune and atopic phenomena.

Management

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised.

See also

• Susceptibility and severity of infections in pregnancy
• Mouse models of breast cancer metastasis Immunodeficient mice can be used in cancer studies.

External links

• Immune Deficiency Foundation
• The European Society of Immunodeficiencies Biennial Meeting
• The European Society of Immunodeficiencies