Immunodeficiency
 | This articleneeds additional citations forverification.(November 2007) |
| Immunodeficiency | |
|---|---|
| Other names | Immunocompromisation, immune deficiency |
| Specialty | Immunology |
| Medication | Imuran |
Immunodeficiency,also known asimmunocompromisation,is a state in which theimmune system's ability to fightinfectious diseasesandcanceris compromised or entirely absent. Most cases are acquired ( "secondary" ) due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors includeHIVinfection andenvironmental factors,such asnutrition.[1]Immunocompromisation may also be due togenetic diseases/flaws such asSCID.
In clinical settings,immunosuppressionby some drugs, such as steroids, can either be anadverse effector the intended purpose of the treatment. Examples of such use is inorgan transplantsurgery as an anti-rejectionmeasure and in patients with an overactive immune system, as inautoimmune diseases.Some people are born with intrinsic defects in theirimmune system,orprimary immunodeficiency.[2]
A person who has an immunodeficiency of any kind is said to beimmunocompromised.An immunocompromised individual may particularly be vulnerable toopportunistic infections,in addition to normalinfectionsthat could affect anyone.[3]It also decreasescancer immunosurveillance,in which the immune system scans the body's cells and killsneoplasticones. They are also more susceptible to infectious diseases owing to the reduced protection afforded byvaccines.[4][5]
Types
[edit]By affected component
[edit]- Humoral immune deficiency(including B cell deficiency or dysfunction), with signs or symptoms depending on the cause, but generally include signs ofhypogammaglobulinemia(decrease of one or more types of antibodies) with presentations including repeated mildrespiratory infections,and/oragammaglobulinemia(lack of all or most antibody production) which results in frequent severe infections and is often fatal.[6]
- T cell deficiency,often causes secondary disorders such asacquired immune deficiency syndrome(AIDS).[7]
- Granulocyte deficiency,including decreased numbers ofgranulocytes(called asgranulocytopeniaor, if absent,agranulocytosis) such as ofneutrophil granulocytes(termedneutropenia). Granulocyte deficiencies also include decreased function of individual granulocytes, such as inchronic granulomatous disease.
- Asplenia,where there is no function of thespleen
- Complement deficiencyis where the function of thecomplement systemis deficient
In reality, immunodeficiency often affects multiple components, with notable examples includingsevere combined immunodeficiency(which is primary) andacquired immune deficiency syndrome(which is secondary).
| Affected components | Main causes[8] | Main pathogens of resultant infections[8] | |
|---|---|---|---|
| Humoral immune deficiency | B cells,plasma cellsorantibodies | ||
| T cell deficiency | T cells |
|
Intracellular pathogens,includingHerpes simplex virus,Mycobacterium,Listeria,[9]and intracellularfungal infections.[8] |
| Neutropenia | Neutrophil granulocytes |
|
|
| Asplenia | Spleen | ||
| Complement deficiency | Complement system |
|
Primary or secondary
[edit]The distinction between primary versus secondary immunodeficiencies is 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
[edit]A number ofrare diseasesfeature a heightened susceptibility toinfectionsfrom childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies.[11]Many of these disorders arehereditaryand areautosomal recessiveorX-linked.There are over 95 recognised primary immunodeficiency syndromes; they are generally grouped by the part of the immune system that is malfunctioning, such aslymphocytesorgranulocytes.[12]
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.The characteristics of lacking and/or impaired antibody functions can be related to illnesses such as X-Linked Agammaglobulinemia and Common Variable Immune Deficiency[13]
Secondary immunodeficiencies
[edit]Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from variousimmunosuppressiveagents, for example,malnutrition,aging,particular medications (e.g.,chemotherapy,disease-modifying antirheumatic drugs,immunosuppressive drugsafterorgan transplants,glucocorticoids) andenvironmental toxinslikemercuryand otherheavy metals,pesticidesandpetrochemicalslikestyrene,dichlorobenzene,xylene,andethylphenol.For medications, the termimmunosuppressiongenerally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the termimmunodeficiencygenerally refers solely to the adverse effect of increased risk for infection.
Many specific diseases directly or indirectly cause immunosuppression. This includes many types ofcancer,particularly those of the bone marrow and blood cells (leukemia,lymphoma,multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark ofacquired immunodeficiency syndrome(AIDS),[11]caused by thehuman immunodeficiency virus(HIV). HIV directly infects a small number ofT helper cells,and also impairs other immune system responses indirectly.
Various hormonal and metabolic disorders can also result in immune deficiency including anemia, hypothyroidism and hyperglycemia.
Smoking, alcoholism and drug abuse also depress immune response.
Heavy schedules of training and competition in athletes increases their risk of immune deficiencies.[14]
Causes
[edit]The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired by malnutrition and poor sanitary conditions.[15][16]Only for some genetic causes, the exact genes are known.[17]
Immunodeficiency and autoimmunity
[edit] | This sectionneeds additional citations forverification.(November 2016) |
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.[18] One example iscommon variable immunodeficiency(CVID) where multiple autoimmune diseases are seen, e.g.,inflammatory bowel disease,autoimmunethrombocytopenia,and autoimmune thyroid disease. Familial hemophagocytic lymphohistiocytosis,an autosomal recessive primary immunodeficiency, is another example.Low blood levels of red blood cells, white blood cells, and platelets,rashes,lymph node enlargement,andenlargement of the liver and spleenare commonly seen in these patients. Presence of multiple uncleared viral infections due to lack ofperforinare 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 inX-linked agammaglobulinemia(XLA). Recurrent bacterial and fungal infections and chronic inflammation of the gut and lungs are seen inchronic granulomatous disease(CGD) as well. CGD is caused by a decreased production ofnicotinamide adenine dinucleotide phosphate(NADPH) oxidase byneutrophils. Hypomorphic RAG mutations are seen in patients withmidline granulomatous disease;an autoimmune disorder that is commonly seen in patients withgranulomatosis with polyangiitisand NK/T cell lymphomas. Wiskott–Aldrich syndrome(WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma. Inautoimmune 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.
Diagnosis
[edit]Medical History and Physical Examination: A physician will inquire about past illnesses and family history of immune disorders to identify inherited conditions. A detailed physical examination helps recognize symptoms indicative of an immune disorder. Blood Tests: these tests are instrumental in diagnosing immunodeficiency as they measure: Infection-fighting proteins (immunoglobulins): Essential for robust immune defense, these protein levels are measured to evaluate immune function.[19]Blood cell counts: Deviations in specific blood cells can point to an immune system anomaly. Immune system cells: These assessments are used to measure the levels of various immune cells. Genetic testing involves collecting samples from patients for molecular analysis when there is a suspicion of inborn errors in immunity. Most Primary Immunodeficiency Disorders (PIDs) are inherited as single-gene defects.[20]The key genes associated with immunodeficiency diseases include CD40L, CD40, RAG1, RAG2, IL2RG, and ADA. Here is a summary of some methods utilized to identify genetic anomalies: Sanger Sequencing of Single Genes: Sanger sequencing is widely recognized as the benchmark method for accurately identifying individual nucleotide changes, as well as small-scale insertions or deletions in DNA. It is particularly valuable for confirming known familial genetic variations, for validating findings from next-generation sequencing technologies, and in specific scenarios that require sequencing of single genes. An example is its use to confirm mutations in the Bruton tyrosine kinase (BTK) gene, which are linked to X-linked agammaglobulinemia (XLA)[21] • Targeted Gene Sequencing Panels (tNGS): This technology is ideal for examining genes in specific pathways or for follow-up experiments (targeted resequencing) from whole genome sequencing (WGS). It is rapid and more cost-effective than WGS, and because it allows for deeper sequencing.[22] • Whole Exome Sequencing (WES): is a commonly used method which captures the majority of coding regions of the genome for sequencing, as these regions contain the majority of disease-causing mutations Useful for identifying mutations in specific genes[23] • Trio or Whole-Family Analyses: In some cases, analyzing the DNA of the patient, parents, and siblings (trio analysis) or the entire family (whole-family analysis) can reveal inheritance patterns and identify causative mutations[24]
Treatment
[edit]Available treatment falls into two modalities: treating infections and boosting the immune system.
Prevention ofPneumocystis pneumoniausingtrimethoprim/sulfamethoxazoleis useful in those who are immunocompromised.[25]In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administered, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.[13]
Prognosis
[edit]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
[edit]- Acquired immune deficiency syndrome(AIDS)
- 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 likeprednisonethat suppress the immune system
- Human genetic enhancement
- Immune system
- Immunology
References
[edit]- ^Chinen J, Shearer WT (February 2010)."Secondary immunodeficiencies, including HIV infection".The Journal of Allergy and Clinical Immunology.125(2 Suppl 2): S195–203.doi:10.1016/j.jaci.2009.08.040.PMC6151868.PMID20042227.
- ^"Primary immunodeficiency".Mayo Clinic. 30 January 2020.Retrieved13 May2020.
- ^Meidani, Mohsen; Naeini, Alireza Emami; Rostami, Mojtaba; Sherkat, Roya; Tayeri, Katayoun (March 2014)."Immunocompromised patients: Review of the most common infections happened in 446 hospitalized patients".Journal of Research in Medical Sciences.19(Suppl 1): S71–S73pmc=4078380.PMC4078380.PMID25002900.
- ^Lee, Ainsley Ryan Yan Bin; Wong, Shi Yin; Chai, Louis Yi Ann; Lee, Soo Chin; Lee, Matilda Xinwei; Muthiah, Mark Dhinesh; Tay, Sen Hee; Teo, Chong Boon; Tan, Benjamin Kye Jyn; Chan, Yiong Huak; Sundar, Raghav; Soon, Yu Yang (2 March 2022)."Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis".BMJ.376:e068632.doi:10.1136/bmj-2021-068632.PMC8889026.PMID35236664.
- ^Zbinden, Delphine; Manuel, Oriol (February 2014). "Influenza vaccination in immunocompromised patients: efficacy and safety".Immunotherapy.6(2): 131–139.doi:10.2217/imt.13.171.PMID24491087.
- ^Greenberg S."Immunodeficiency".University of Toronto. Archived fromthe originalon 10 July 2013.
- ^Schwartz RA (2019-10-22). Jyonouchi H (ed.)."T-cell Disorders".Medscape.
- ^abcIf not otherwise specified in boxes, then reference for entries is:Page 432,Chapter 22, Table 22.1 in:Jones J, Bannister BA, Gillespie SH (2006).Infection: Microbiology and Management.Wiley-Blackwell.ISBN978-1-4051-2665-6.
- ^Page 435in:Jones J, Bannister BA, Gillespie SH (2006).Infection: Microbiology and Management.Wiley-Blackwell.ISBN978-1-4051-2665-6.
- ^abcdBrigden ML (February 2001). "Detection, education and management of the asplenic or hyposplenic patient".American Family Physician.63(3): 499–506, 508.PMID11272299.
- ^abBasic Immunology: Functions and Disorders of the Immune System, 3rd Ed. 2011.
- ^Rosen FS, Cooper MD, Wedgwood RJ (August 1995). "The primary immunodeficiencies".The New England Journal of Medicine.333(7): 431–40.doi:10.1056/NEJM199508173330707.PMID7616993.S2CID39699189.
- ^ab"Immune Deficiency Foundation".primaryimmune.org.Retrieved2017-04-17.
- ^Gleeson, Michael; Nieman, David C; Pedersen, Bente K (January 2004). "Exercise, nutrition and immune function".Journal of Sports Sciences.22(1): 115–125.doi:10.1080/0264041031000140590.PMID14971437.S2CID84378380.
- ^"Nutrition and Immunity".The Nutrition Source.Harvard T.H. Chan School of Public Health. May 2020.Retrieved8 November2020.
- ^Bourke CD, Berkley JA, Prendergast AJ (2016)."Immune Dysfunction as a Cause and Consequence of Malnutrition".Trends in Immunology.37(6): 386–398.doi:10.1016/j.it.2016.04.003.PMC4889773.PMID27237815.
- ^Charles A Janeway, Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J. (2001)."Inherited immunodeficiency diseases".Immunobiology.Garland Science.
- ^Grammatikos AP, Tsokos GC (February 2012)."Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus".Trends in Molecular Medicine.18(2): 101–8.doi:10.1016/j.molmed.2011.10.005.PMC3278563.PMID22177735.
- ^"Primary immunodeficiency - Diagnosis and treatment".Mayo Clinic.
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- ^FERNANDEZ, JAMES."Overview of Immunodeficiency Disorders. Merck Manuals Consumer Version".
- ^von Hardenberg, Sandra; Klefenz; Steinemann (2024)."Current genetic diagnostics in inborn errors of immunity".Frontiers in Pediatrics.12.doi:10.3389/fped.2024.1279112.PMC11039790.PMID38659694.
- ^von Hardenberg, Sandra (2024)."Pediatric Immunology Volume 12".Frontiers in Pediatrics.12.doi:10.3389/fped.2024.1279112.PMC11039790.PMID38659694.
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- ^Stern A, Green H, Paul M, Vidal L, Leibovici L (October 2014)."Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients".The Cochrane Database of Systematic Reviews.10(10): CD005590.doi:10.1002/14651858.CD005590.pub3.PMC6457644.PMID25269391.
