Immunodeficiency
| Immune deficiency | |
|---|---|
| Classification and external resources | |
| Specialty | hematology |
| 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 and cancer is compromised or entirely absent. Most cases of immunodeficiency are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection, extremes of age, and environmental factors, such as nutrition.[1] In the clinical setting, the immunosuppression by some drugs, such as steroids, can be either an adverse effect or the intended purpose of the treatment. Examples of such use is in organ transplant surgery as an anti-rejection measure and in patients suffering from an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency. 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. Immunodeficiency also decreases cancer immunosurveillance, in which the immune system scans the body's cells and kills neoplastic ones.
Types
By affected component
- Humoral immune deficiency (including B cell deficiency or dysfunction), 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.[2]
- T cell deficiency, often causes secondary disorders such as acquired immune deficiency syndrome (AIDS).[3]
- 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).
| Affected components | Main causes[4] | Main pathogens of resultant infections[4] | |
|---|---|---|---|
| Humoral immune deficiency | B cells, plasma cells or antibodies | ||
| T cell deficiency | T cells |
|
Intracellular pathogens, including Herpes simplex virus, Mycobacterium, Listeria,[5] and intracellular fungal infections.[4] |
| Neutropenia | Neutrophil granulocytes |
|
|
| Asplenia | Spleen |
| |
| Complement deficiency | Complement system |
|
|
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
A number of rare diseases feature a heightened susceptibility to infections from childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies.[7] 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.[8]
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
Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example, malnutrition, aging, particular medications (e.g., chemotherapy, disease-modifying antirheumatic drugs, immunosuppressive drugs after organ transplants, glucocorticoids) and environmental toxins like mercury and other heavy metals, pesticides and petrochemicals like styrene, dichlorobenzene, xylene, and ethylphenol. 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),[7] 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.
Various hormonal and metabolic disorders can also result in immune deficiency including anemia, hypothyroidism, diabetes and hypoglycemia.
Smoking, alcoholism and drug abuse also depress immune response.
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.[9]
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.
Causes
The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired, or both.
Treatment
Available treatment falls into two modalities: treating infections and boosting the immune system.
Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised.[10]
Prognosis
Prognosis depends greatly on the nature and severity of the condition. Some deficiencies cause early mortality (before age one), others with or even without treatment are lifelong conditions that cause little mortality or morbidity. Newer stem cell transplant technologies may lead to gene based treatments of debilitating and fatal genetic immune deficiencies. Prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or condition (like AIDS).
See also
- Acquired immune deficiency syndrome (AIDS or HIV)), a viral disease sometimes colloquially used as synonymous with immune deficiency
- Immune disorder
- Autoimmune disease, immune response to self-proteins
- Allergy, immune response to harmless non-self proteins
- Immunosenescence, age-associated immune deficiency
- Steroids, commonly administered drugs like prednisone that suppress the immune system
- Immune system
- Immunology
References
- ↑ Chinen, J. and Shearer, W. (2010) ‘Secondary Immunodeficiencies, including HIV infection’, Journal of Allergy and Clinical Immunology, 125(2), pp. 195-203.
- ↑ Immunodeficiency by Dr. Saul Greenberg. University of Toronto. Last updated, on February 5, 2009
- ↑ Medscape > T-cell Disorders. Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD. Updated: May 16, 2011
- 1 2 3 If not otherwise specified in boxes, then reference for entries is: Page 432, Chapter 22, Table 22.1 in: Jones, Jane; Bannister, Barbara A.; Gillespie, Stephen H. (2006). Infection: Microbiology and Management. Wiley-Blackwell. ISBN 1-4051-2665-5.
- ↑ Page 435 in: Jones, Jane; Bannister, Barbara A.; Gillespie, Stephen H. (2006). Infection: Microbiology and Management. Wiley-Blackwell. ISBN 1-4051-2665-5.
- 1 2 3 4 Brigden, M. L. (2001). "Detection, education and management of the asplenic or hyposplenic patient". American family physician. 63 (3): 499–506, 508. PMID 11272299.
- 1 2 Basic Immunology: Functions and Disorders of the Immune System, 3rd Ed. 2011.
- ↑ Rosen FS, Cooper MD, Wedgwood RJ (1995). "The primary immunodeficiencies". N. Engl. J. Med. 333 (7): 431–40. doi:10.1056/NEJM199508173330707. PMID 7616993.
- ↑ Grammatikos A, Tsokos G (2012). "Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus". Trends Mol Med. 18 (2): 101–108. doi:10.1016/j.molmed.2011.10.005. PMC 3278563
. PMID 22177735. - ↑ Stern, A; Green, H; Paul, M; Vidal, L; Leibovici, L (Oct 1, 2014). "Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients.". The Cochrane database of systematic reviews. 10: CD005590. doi:10.1002/14651858.CD005590.pub3. PMID 25269391.