Immunodeficiency

Last updated
Immunodeficiency
Other namesImmunocompromisation, immune deficiency
Specialty Immunology
Medication Imuran

Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is 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 include HIV infection and environmental factors, such as nutrition. [1] Immunocompromisation may also be due to genetic diseases/flaws such as SCID.

Contents

In clinical settings, immunosuppression by some drugs, such as steroids, can either be 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 with an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency. [2]

A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised individual may particularly be vulnerable to opportunistic infections, in addition to normal infections that could affect anyone. [3] It also decreases cancer immunosurveillance, in which the immune system scans the body's cells and kills neoplastic ones. They are also more susceptible to infectious diseases owing to the reduced protection afforded by vaccines. [4] [5]

Types

By affected component

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 componentsMain causes [8] Main pathogens of resultant infections [8]
Humoral immune deficiency

B cell deficiency

B cells, plasma cells or antibodies
T cell deficiency T cells Intracellular pathogens, including Herpes simplex virus , Mycobacterium , Listeria , [9] and intracellular fungal infections. [8]
Neutropenia Neutrophil granulocytes
Asplenia Spleen
Complement deficiency Complement system
  • Congenital deficiencies

Primary or secondary

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

A number of rare diseases feature a heightened susceptibility to infections from childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies. [11] Many of these disorders are hereditary and are autosomal recessive or X-linked. There are over 95 recognised primary immunodeficiency syndromes; they are generally grouped by the part of the immune system that is malfunctioning, such as lymphocytes or granulocytes. [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

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), [11] 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 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

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

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 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. Low blood levels of red blood cells, white blood cells, and platelets, rashes, lymph node enlargement, and enlargement of the liver and spleen 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 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.

Diagnosis

Patients with immune deficiencies can present with variable clinical phenotypes. This often translates into a significant delay in their diagnosis, and resultant patient morbidity. A structured approach on when to suspect an immunodeficiency and the initial investigations pathway is given in the publication by Grammatikos et al. [19]

People who suffer from chronic infections such as candida or lyme disease have predisposed or enhanced immune responses. So, individuals with underlying conditions such as periodic(chronic) bacterial pneumonias, yeast infections, bacterial sinus infections, and other continuous infections are at a very high risk of being diganosed with an immunodeficiency disorder. By undermining the immune system, people susceptible to chronic illnesses suffer from existing illnesses constantly, forming a sick circle. Besides that, they may also suffer from chronic abdominal pain and this will further complicate their condition while as the time passes they lead to weight loss due to impaired metabolism and maintenance of overall wellbeing. [20]

If a doctor suspects for a immunodeficiency, they will proceed with conducting multiple different effectual tests. The tests depend on the type of immunodeficiency you may have. Primary immunodeficiencies are in most cases hereditary, more specifically X-linked. Secondary immunodeficiencies are brought about by malnutrition, aging, and certain medications. In most cases, the doctor begins from the review of the patient's medical record, followed by a comprehensive physical exam. A laboratory assay to test for the fraction of white blood cell, T cell, and immunoglobulin amounts will be crucial for diagnosis. Skin tests may be used as the investigative tool in situations where a T cell abnormality is suspected. Making biopsies of lymph nodes or marrow may be the case when determining the underlying causes of the disease. A genetic test involves a blood sample usually ordered to look for the specific gene mutations ratifying the influence to the immune disorder. Such diagnostic tests comprise of instruments that individually give the clue on the specific disorder and assist in the development of effective treatment regimens. [21]

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. [22] 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

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

Related Research Articles

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Immunosuppression</span> Decreased resistance to infection

Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions.

<span class="mw-page-title-main">Adenosine deaminase deficiency</span> Medical condition

Adenosine deaminase deficiency is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immunodeficiency (SCID) after excluding disorders related to inbreeding.

<span class="mw-page-title-main">Wiskott–Aldrich syndrome</span> Medical condition

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhea. It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present with similar but less severe symptoms and are caused by mutations of the same gene.

<span class="mw-page-title-main">X-linked agammaglobulinemia</span> Medical condition

X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the white blood cell formation process does not generate mature B cells, which manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream. B cells are part of the immune system and normally manufacture antibodies, which defend the body from infections by sustaining a humoral immunity response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development and a reduced immunoglobulin production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.

Hypogammaglobulinemia is an immune system disorder in which not enough gamma globulins are produced in the blood. This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as medication, blood cancer, or poor nutrition, or loss of gamma globulins in urine, as in nonselective glomerular proteinuria. Patients with hypogammaglobulinemia have reduced immune function; important considerations include avoiding use of live vaccines, and take precautionary measures when traveling to regions with endemic disease or poor sanitation such as receiving immunizations, taking antibiotics abroad, drinking only safe or boiled water, arranging appropriate medical cover in advance of travel, and ensuring continuation of any immunoglobulin infusions needed.

Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA. Symptoms generally include high susceptibility to pathogens, chronic lung disease, as well as inflammation and infection of the gastrointestinal tract.

<span class="mw-page-title-main">Complement component 2</span> Protein found in humans

Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases.

<span class="mw-page-title-main">Hyper IgM syndrome</span> Primary immune deficiency disorders

Hyper IgM syndrome is a rare primary immune deficiency disorders characterized by low or absent levels of serum IgG, IgA, IgE and normal or increased levels of serum IgM.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins. Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 430 recognized inborn errors of immunity (IEIs) as of 2019, the vast majority of which are PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, auto-inflammatory disorders, tumors, and disorders of various organs. There are currently limited treatments available for these conditions; most are specific to a particular type of PID. Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs.

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:

<span class="mw-page-title-main">Humoral immune deficiency</span> Medical condition

Humoral immune deficiencies are conditions which cause impairment of humoral immunity, which can lead to immunodeficiency. It can be mediated by insufficient number or function of B cells, the plasma cells they differentiate into, or the antibody secreted by the plasma cells. The most common such immunodeficiency is inherited selective IgA deficiency, occurring between 1 in 100 and 1 in 1000 persons, depending on population. They are associated with increased vulnerability to infection, but can be difficult to detect in the absence of infection.

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

Thymoma with immunodeficiency is a rare disorder that occurs in adults in whom hypogammaglobulinemia, deficient cell-mediated immunity, and thymoma may develop almost simultaneously. Most reported cases are in Europe, though it occurs globally.

<span class="mw-page-title-main">X-linked reticulate pigmentary disorder</span> Rare X-linked genetic condition

X-linked reticulate pigmentary disorder is a rare X-linked genetic condition in which males manifest multiple systemic symptoms and a reticulated mottled brown pigmentation of the skin, which, on biopsy, demonstrated dermal deposits of amyloid. Females usually only have linear streaks of hyperpigmentation.

<span class="mw-page-title-main">XMEN disease</span> Medical condition

XMEN disease is a rare genetic disorder of the immune system that illustrates the role of glycosylation in the function of the immune system. XMEN stands for “X-linked MAGT1 deficiency with increased susceptibility to Epstein–Barr virus (EBV) infection and N-linked glycosylation defect.” The disease is characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. Investigators in the laboratory of Dr. Michael Lenardo, National Institute of Allergy and Infectious Diseases at the National Institutes of Health first described this condition in 2011.

<span class="mw-page-title-main">RAS-associated autoimmune leukoproliferative disorder</span> Medical condition

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain–Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.

Autoinflammatory diseases (AIDs) are a group of rare disorders caused by dysfunction of the innate immune system. These responses are characterized by periodic or chronic systemic inflammation, usually without the involvement of adaptive immunity.

References

  1. ↑ 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. PMC   6151868 . PMID   20042227.
  2. ↑ "Primary immunodeficiency". Mayo Clinic. 30 January 2020. Retrieved 13 May 2020.
  3. ↑ 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. PMC   4078380 . PMID   25002900.
  4. ↑ 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. PMC   8889026 . PMID   35236664.
  5. ↑ 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. PMID   24491087.
  6. ↑ Greenberg S. "Immunodeficiency". University of Toronto. Archived from the original on 10 July 2013.
  7. ↑ Schwartz RA (2019-10-22). Jyonouchi H (ed.). "T-cell Disorders". Medscape.
  8. 1 2 3 If 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. ISBN   978-1-4051-2665-6.
  9. ↑ Page 435 in: Jones J, Bannister BA, Gillespie SH (2006). Infection: Microbiology and Management. Wiley-Blackwell. ISBN   978-1-4051-2665-6.
  10. 1 2 3 4 Brigden ML (February 2001). "Detection, education and management of the asplenic or hyposplenic patient". American Family Physician. 63 (3): 499–506, 508. PMID   11272299.
  11. 1 2 Basic Immunology: Functions and Disorders of the Immune System, 3rd Ed. 2011.
  12. ↑ 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. PMID   7616993. S2CID   39699189.
  13. 1 2 "Immune Deficiency Foundation". primaryimmune.org. Retrieved 2017-04-17.
  14. ↑ 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. PMID   14971437. S2CID   84378380.
  15. ↑ "Nutrition and Immunity". The Nutrition Source. Harvard T.H. Chan School of Public Health. May 2020. Retrieved 8 November 2020.
  16. ↑ 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 . PMC   4889773 . PMID   27237815.
  17. ↑ Charles A Janeway, Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J. (2001). "Inherited immunodeficiency diseases". Immunobiology. Garland Science.
  18. ↑ 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. PMC   3278563 . PMID   22177735.
  19. ↑ Grammatikos, Alexandros; Bright, Philip; Bhatnagar, Rahul; Johnston, Sarah (September 2020). "How to investigate a suspected immune deficiency in adults". Respiratory Medicine. 171: 106100. doi: 10.1016/j.rmed.2020.106100 . PMID   32799060. S2CID   221143773.
  20. ↑ Meyts, Isabelle; Bousfiha, Aziz; Duff, Carla; Singh, Surjit; Lau, Yu Lung; Condino-Neto, Antonio; Bezrodnik, Liliana; Ali, Adli; Adeli, Mehdi; Drabwell, Jose (2021-02-18). "Primary Immunodeficiencies: A Decade of Progress and a Promising Future". Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.625753 . ISSN   1664-3224. PMC   7935502 . PMID   33679719.
  21. ↑ Meyts, Isabelle; Bousfiha, Aziz; Duff, Carla; Singh, Surjit; Lau, Yu Lung; Condino-Neto, Antonio; Bezrodnik, Liliana; Ali, Adli; Adeli, Mehdi; Drabwell, Jose (2021-02-18). "Primary Immunodeficiencies: A Decade of Progress and a Promising Future". Frontiers in Immunology. 11. doi: 10.3389/fimmu.2020.625753 . ISSN   1664-3224. PMC   7935502 . PMID   33679719.
  22. ↑ 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. PMC   6457644 . PMID   25269391.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.