Autoimmune polyendocrine syndrome type 2

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Autoimmune polyendocrine syndrome type 2
Other namesSchmidt's syndrome [1]
HLA-DQ2.5 gliadin.PNG
HLA-DQ2 one of the human leukocyte antigens genotypes responsible for this condition
Specialty Endocrinology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Asplenia [1]
Risk factors Human leukocyte antigen (HLA-DQ2, HLA-DQ8 and HLA-DR4) [2]
Diagnostic method Ultrasound, MRI [3]
TreatmentThyroid-stimulating hormone [4]

Autoimmune polyendocrine syndrome type 2, a form of autoimmune polyendocrine syndrome also known as APS-II, or PAS II, is the most common form of the polyglandular failure syndromes. [2] PAS II is defined as the association between autoimmune Addison's disease and either autoimmune thyroid disease, type 1 diabetes, or both. [5] It is heterogeneous and has not been linked to one gene. Rather, individuals are at a higher risk when they carry a particular human leukocyte antigen (HLA-DQ2, HLA-DQ8 and HLA-DR4). APS-II affects women to a greater degree than men. [2]

Contents

Signs and symptoms

Signs and symptoms that are consistent in an individual affected with autoimmune polyendocrine syndrome type 2 are the following: [1] [4] [6]

Hashimoto thyroiditis Hashimoto thyroiditis - alt -- very low mag.jpg
Hashimoto thyroiditis

Genetics

HLA(haplotypes) Whla 03.jpg
HLA(haplotypes)

In terms of genetics one finds that autoimmune polyendocrine syndrome type 2 has an autosomal dominant pattern of inheritance, with an incomplete penetrance. [7] [8] Furthermore, the human leukocyte antigen involved in this condition are HLA-DQ2(DR3 (DQB*0201)) and HLA-DQ8(DR4 (DQB1*0302)), [9] genetically speaking, which indicates this is a multifactorial disorder, as well. [1] [10]

Should any affected organs show chronic inflammatory infiltrate (lymphocytes), this would be an indication. Moreover, autoantibodies reacting to specific antigens is common, in the immune system of an affected individual. [4]

Diagnosis

In terms of genetic testing, while it is done for type 1 of this condition, type 2 will only render (or identify) those genes which place the individual at higher risk. [11] Other methods/exam to ascertain if an individual has autoimmune polyendocrine syndrome type 2 are: [3]

Treatment

Type of glucocorticoid Cortisol2.svg
Type of glucocorticoid

Management of autoimmune polyendocrine syndrome type 2 consists of the following: [4]

History

The condition was recognized by Martin Benno Schmidt (1863 – 1949), a German pathologist, first described in 1926. [12] A third subtype, PAS III, has been described in adults, but apart from the absence of adrenal failure, no clinical differences between types II and III have been described. Because of this, both of these subtypes are generally referred to as PAS II. [13] [14]

Society and culture

See also

Related Research Articles

<span class="mw-page-title-main">Autoimmune polyendocrine syndrome</span> Medical condition

Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs) or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three types of APS, and there are a number of other diseases which involve endocrine autoimmunity.

Slowly evolving immune-mediated diabetes, or latent autoimmune diabetes in adults (LADA), is a form of diabetes that exhibits clinical features similar to both type 1 diabetes (T1D) and type 2 diabetes (T2D), and is sometimes referred to as type 1.5 diabetes. It is an autoimmune form of diabetes, similar to T1D, but patients with LADA often show insulin resistance, similar to T2D, and share some risk factors for the disease with T2D. Studies have shown that LADA patients have certain types of antibodies against the insulin-producing cells, and that these cells stop producing insulin more slowly than in T1D patients. Since many people develop the disease later in life, it is often misdiagnosed as type 2 diabetes.

<span class="mw-page-title-main">HLA-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

HLA DR3-DQ2 is a double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

<span class="mw-page-title-main">HLA-DQ8</span>

HLA-DQ8 (DQ8) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ8 is a split antigen of the DQ3 broad antigen. DQ8 is determined by the antibody recognition of β8 and this generally detects the gene product of DQB1*0302.

<span class="mw-page-title-main">Autoimmune regulator</span> Immune system protein

The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kbp gene on chromosome 21q22.3 that encodes 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.

<span class="mw-page-title-main">Endocrine disease</span> Disorders of the endocrine system

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

<span class="mw-page-title-main">Gluten-related disorders</span> Set of diseases caused by gluten exposure

Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.

<span class="mw-page-title-main">HLA-DQ2</span> Human leukocyte antigen serotype

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DQ7</span>

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DQB1*0301 and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

<span class="mw-page-title-main">HLA-DR17</span>

HLA-DR17 (DR17) is an HLA-DR serotype that recognizes the DRB1*0301 and *0304 gene products. DR17 is found at high frequency in Western Europe. DR17 is part of the broader antigen group HLA-DR3 and is very similar to the group HLA-DR18.

<span class="mw-page-title-main">HLA-DR3</span>

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is associated with HLA-DR3 or HLA-DR4. Nearly half the US population has either DR3 or DR4, yet only a small percentage of these individuals will develop type 1 diabetes.

<span class="mw-page-title-main">HLA-DR4</span>

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.

<span class="mw-page-title-main">HLA-A1</span> Human leukocyte antigen serotype

HLA-A1 (A1) is a human leukocyte antigen serotype within HLA-A "A" serotype group. The serotype is determined by the antibody recognition of α1 subset of HLA-A α-chains. For A1, the alpha "A" chain are encoded by the HLA-A*01 allele group and the β-chain are encoded by B2M locus. This group currently is dominated by A*01:01. A1 and A*01 are almost synonymous in meaning. A1 is more common in Europe than elsewhere, it is part of a long haplotype that appears to have been frequent in the ancient peoples of Northwestern Europe. A1 is a frequent component of the AH8.1 haplotype. A1 serotype positivity is roughly linked to a large number of inflammatory diseases and conditions believed to have immune system involvement. Because of its linkage within the AH8.1 haplotype many studies showed association with A1 or A1,B8 only later to show the association drift toward the class II region gene alleles, DR3 and DQ2.5. While it is not clear what role A1 has in infectious disease, some linkage with infection rates in HIV remain associated within the A1 region of the haplotype.

HLA A1-B8-DR3-DQ2 haplotype is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

HLA A1-B8 is a multigene haplotype that covers the MHC Class I region of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of identity by descent from a common ancestor. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

<span class="mw-page-title-main">Autoimmune polyendocrine syndrome type 1</span> Autoimmune condition causing dysfunction of endocrine glands

Autoimmune polyendocrine syndrome type 1 (APS-1), is a subtype of autoimmune polyendocrine syndrome. It causes the dysfunction of multiple endocrine glands due to autoimmunity. It is a genetic disorder, inherited in autosomal recessive fashion due to a defect in the AIRE gene , which is located on chromosome 21 and normally confers immune tolerance.

Autoimmune polyendocrine syndrome, type 3 is a condition characterized by the coexistence of autoimmune thyroiditis and at least one other autoimmune disease. Based on other organ-specific autoimmune involvement, there are multiple subtypes that are classified: type 3a shows thyroid autoimmune disease in conjunction with type 1 diabetes, type 3b shows thyroid autoimmune disease in conjunction with pernicious anemia (PA), and type 3c shows thyroid autoimmune disease in conjunction with alopecia, vitiligo, or other organ-specific autoimmune disease.

Ludvig M. Sollid is a Norwegian physician-scientist whose laboratory has made discoveries in the pathogenesis of HLA associated human disorders, most notably celiac disease. He is currently a Professor of Medicine (immunology) at the University of Oslo and a Senior Consultant at Oslo University Hospital.

References

  1. 1 2 3 4 "Autoimmune polyglandular syndrome type 2 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2017-04-13. Retrieved 2017-04-12.
  2. 1 2 3 Greenspan, Francis S.; Gardner, David C. (2004). Basic clinical endocrinology . New York: McGraw-Hill. pp.  103. ISBN   978-0-07-140297-2.
  3. 1 2 Betterle, C; Lazzarotto, F; Presotto, F (19 April 2017). "Autoimmune polyglandular syndrome Type 2: the tip of an iceberg?". Clinical and Experimental Immunology. 137 (2): 225–233. doi:10.1111/j.1365-2249.2004.02561.x. ISSN   0009-9104. PMC   1809126 . PMID   15270837.
  4. 1 2 3 4 "Type II Polyglandular Autoimmune Syndrome Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Archived from the original on 2017-04-14. Retrieved 2017-04-13.
  5. ↑ Kahaly, George J. (2012-12-01). "Polyglandular Autoimmune Syndrome Type II". La Presse Médicale. 41 (12): e663–e670. doi:10.1016/j.lpm.2012.09.011. ISSN   0755-4982. PMID   23159534.
  6. ↑ Betterle C, Zanchetta R (April 2003). "Update on autoimmune polyendocrine syndromes (APS)". Acta Biomed. 74 (1): 9–33. PMID   12817789.
  7. ↑ Betterle, Corrado; Dal Pra, Chiara; Mantero, Franco; Zanchetta, Renato (2002-06-01). "Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction". Endocrine Reviews. 23 (3): 327–364. doi: 10.1210/edrv.23.3.0466 . ISSN   0163-769X. PMID   12050123.
  8. ↑ "OMIM Entry - % 269200 - AUTOIMMUNE POLYENDOCRINE SYNDROME, TYPE II; APS2". omim.org. Archived from the original on 2019-12-15. Retrieved 2017-04-13.
  9. ↑ Majeroni, BA; Patel, P (1 March 2007). "Autoimmune polyglandular syndrome, type II". American Family Physician. 75 (5): 667–70. PMID   17375512. Archived from the original on 14 April 2017. Retrieved 13 April 2017.
  10. ↑ Reference, Genetics Home. "What are complex or multifactorial disorders?". Genetics Home Reference. Archived from the original on 2017-04-19. Retrieved 2017-04-19.
  11. ↑ Weiss, Roy E.; Refetoff, Samuel (2016). Genetic Diagnosis of Endocrine Disorders. Academic Press. p. 367. ISBN   9780128011348. Archived from the original on 14 January 2023. Retrieved 19 April 2017.
  12. ↑ Eisenbarth, George S. (2011). Immunoendocrinology: Scientific and Clinical Aspects. Springer Science & Business Media. p. 143. ISBN   9781603274784 . Retrieved 13 April 2017.
  13. ↑ Kahaly, George J.; Dittmar, Manuela (2003-07-01). "Polyglandular Autoimmune Syndromes: Immunogenetics and Long-Term Follow-Up". The Journal of Clinical Endocrinology & Metabolism. 88 (7): 2983–2992. doi: 10.1210/jc.2002-021845 . ISSN   0021-972X. PMID   12843130.
  14. ↑ Kahaly, George J. (2009-07-01). "Polyglandular autoimmune syndromes". European Journal of Endocrinology. 161 (1): 11–20. doi: 10.1530/EJE-09-0044 . ISSN   1479-683X. PMID   19411300.
  15. ↑ Macchia, Donatella et al. "President John F Kennedy's medical history: coeliac disease and autoimmune polyglandular syndrome type 2." Postgraduate medical journal vol. 96,1139 (2020): 543-549. doi:10.1136/postgradmedj-2020-137722
  16. ↑ Mandel, Lee R. (2009). "Endocrine and Autoimmune Aspects of the Health History of John F. Kennedy". Annals of Internal Medicine. 151 (5): 350–354. doi: 10.7326/0003-4819-151-5-200909010-00011 . PMID   19721023.

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