 | ||
| HLA-B (alpha)-β2MG with bound peptide | ||
major histocompatibility complex (human), class I, B58 | ||
| Alleles | *5801, *5802 | |
| Structure (See HLA-B) | ||
| Shared data | ||
| Locus | chr.6 6p21.31 | |
HLA-B58 (B58) is an HLA-B serotype. B58 is a split antigen from the B17 broad antigen, the sister serotype B57. [1] The serotype identifies the more common HLA-B*58 gene products. [2] (For terminology help see: HLA-serotype tutorial) B*5801 is associated with allopurinol induced inflammatory necrotic skin disease.
| B*58 | B58 | B17 | Sample |
| allele | % | % | size (N) |
| *5801 | 79 | 4 | 2096 |
| *5802 | 72 | 3 | 837 |
| freq | ||
| ref. | Population | (%) |
| [4] | Cameroon Pygmy Baka | 15.0 |
| [4] | India Khandesh Pawra | 15.0 |
| [4] | Cameroon Sawa | 11.5 |
| [4] | Taiwan Hakka | 10.9 |
| [4] | Kenya Nandi | 10.0 |
| [4] | India West Bhils | 9.0 |
| [4] | China South Han | 8.9 |
| [4] | China Inner Mongolia | 8.8 |
| [4] | India North Delhi | 8.8 |
| [4] | Thailand Northeast | 8.4 |
| [4] | Guinea Bissau | 7.8 |
| [4] | Thailand | 7.7 |
| [4] | India Mumbai Marathas | 7.4 |
| [4] | India Andhra Pradesh Golla | 7.2 |
| [4] | Kenya Luo | 7.0 |
| [4] | Senegal Niokholo Mandenka | 6.9 |
| [4] | India New Delhi | 6.8 |
| [4] | Oman | 6.8 |
| [4] | Russia Tuva (2) | 6.7 |
| [4] | South Korea (3) | 6.5 |
| [4] | Italy Sardinia (3) | 6.4 |
| [4] | Burkina Faso Fulani | 6.1 |
| [4] | Taiwan Siraya | 5.9 |
| [4] | India North Hindus | 5.8 |
| [4] | Burkina Faso Mossi | 5.7 |
| [4] | Cameroon Yaounde | 5.4 |
| [4] | Cameroon Bamileke | 5.2 |
| [4] | Singapore Riau Malay | 5.0 |
| [4] | Saudi Arabia Guraiat and Hail | 4.6 |
| [4] | France Corsica | 4.5 |
| [4] | Sudanese | 4.5 |
| [4] | Zimbabwe Harare Shona | 4.4 |
| [4] | Burkina Faso Rimaibe | 4.3 |
| [4] | Iran Baloch | 4.0 |
| [4] | South African Natal Zulu | 4.0 |
| [4] | Tunisia | 4.0 |
| [4] | Uganda Kampala | 4.0 |
| [4] | Cameroon Beti | 3.7 |
| [4] | Tunisia Ghannouch | 3.7 |
| [4] | Taiwan Pazeh | 3.6 |
| [4] | Tunisia Tunis | 3.4 |
| [4] | Italy North (1) | 3.3 |
| [4] | Israel Ashkenazi and Non Ashkenazi Jews | 3.2 |
| [4] | India West Coast Parsis | 3.0 |
| [4] | China North Han | 2.9 |
| [4] | Ivory Coast Akan Adiopodoume | 2.3 |
| [4] | Mali Bandiagara | 2.2 |
| [4] | Mexico Zaptotec Oaxaca | 2.2 |
| [4] | South Africa Natal Tamil | 2.0 |
| [4] | China Yunnan Nu | 1.9 |
| [4] | Bulgaria | 1.8 |
| [4] | China Tibet Autonomous Region Tibetans | 1.6 |
| [4] | France South East | 1.6 |
| [4] | Israel Arab Druse | 1.5 |
| [4] | Czech Republic | 1.4 |
| [4] | Georgia Tbilisi Georgians | 1.4 |
| [4] | Jordan Amman | 1.4 |
| [4] | Morocco Nador Metalsa (berber) | 1.4 |
| [4] | Croatia | 1.3 |
| [4] | Romanian | 1.3 |
| [4] | Spain Eastern Andalusia | 1.2 |
| [4] | Australian Aborigine Cape York Peninsula | 1.0 |
| B*5802 | ||
| [4] | Cameroon Bamileke | 14.3 |
| [4] | Kenya Luo | 12.5 |
| [4] | Cameroon Yaounde | 10.9 |
| [4] | Cameroon Pygmy Baka | 10.0 |
| [4] | Cameroon Beti | 9.8 |
| [4] | Kenya Nandi | 8.5 |
| [4] | South African Natal Zulu | 8.5 |
| [4] | Cameroon Sawa | 7.7 |
| [4] | Zimbabwe Harare Shona | 6.4 |
| [4] | Cape Verde Northwestern Islands | 5.6 |
| [4] | Uganda Kampala | 4.4 |
| [4] | Central Africa Republic Mbenzele Pygmy | 4.0 |
| [4] | Zambia Lusaka | 2.3 |
| [4] | Iran Baloch | 1.0 |
| [4] | Tunisia | 1.0 |
HLA-B*5801 is involved in allopurinol sensitive drug induced Stevens–Johnson syndrome. [5] [6] Allopurinol is a frequent cause of severe cutaneous adverse reactions, including drug-hypersensitivity syndrome, Stevens–Johnson syndrome, and toxic epidermal necrolysis (SJS/TEN). [7] The association with allopurinol sensitivity in SJS/TEN was extremely strong in Asia, and somewhat less associated in Europeans. [8]
Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous drug reactions and probably part of the same spectrum of disease, with SJS being less severe. Erythema multiforme (EM) is generally considered a separate condition. Early symptoms of SJS include fever and flu-like symptoms. A few days later, the skin begins to blister and peel, forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia and multiple organ failure.
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken orally or intravenously.
Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later the skin begins to blister and peel forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia, and multiple organ failure.
HLA-B is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
HLA-A33 (A33) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α33 subset of HLA-A α-chains. For A33, the alpha "A" chain are encoded by the HLA-A*33 allele group and the β-chain are encoded by B2M locus. A33 and A*33 are almost synonymous in meaning. A33 is a split antigen of the broad antigen serotype A19. A33 is a sister serotype of A29, A30, A31, A32, and A74.
Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities such as an abnormally high level of eosinophils, low number of platelets, and increased number of atypical white blood cells (lymphocytes). However, DRESS is often complicated by potentially life-threatening inflammation of internal organs and the syndrome has about a 10% mortality rate. Treatment consists of stopping the offending medication and providing supportive care. Systemic corticosteroids are commonly used as well but no controlled clinical trials have assessed the efficacy of this treatment.
HLA-B17 (B17) is an HLA - B serotype. B17 is a broad antigen serotype that recognizes the B57 and B58 split antigen serotypes. B17 is still encountered in the current literature, although most studies now use B57/B58 or gene typing designators. Both serotypes are involved in slightly different drug-sensitive diseases.
HLA-B57 (B57) is an HLA-B serotype. B57 is a split antigen from the B17 broad antigen, the sister serotype being B58. The serotype identifies the more common HLA-B*57 gene products. Like B58, B57 is involved in drug-induced inflammatory skin disorders.
HLA-B15 (B15) is an HLA-B serotype. The serotype identifies the B*15 gene-allele protein products of HLA-B.
HLA-B75 (B75) is an HLA-B serotype. The serotype identifies certain B*15 gene-allele protein products of HLA-B.
In medicine, a drug eruption is an adverse drug reaction of the skin. Most drug-induced cutaneous reactions are mild and disappear when the offending drug is withdrawn. These are called "simple" drug eruptions. However, more serious drug eruptions may be associated with organ injury such as liver or kidney damage and are categorized as "complex". Drugs can also cause hair and nail changes, affect the mucous membranes, or cause itching without outward skin changes.
Allopurinol hypersensitivity syndrome(AHS) typically occurs in persons with preexisting kidney failure. Weeks to months after allopurinol is begun, the patient develops a morbilliform eruption or, less commonly, develops one of the far more serious and potentially lethal severe cutaneous adverse reactions viz., the DRESS syndrome, Stevens Johnson syndrome, or toxic epidermal necrolysis. About 1 in 1000 patients receiving allopurinol are affected, and mortality rates have been reported to be between 20% and 25%.
Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction that in 90% of cases is related to medication.
Generalized bullous fixed drug eruption (GBFDE) most commonly refers to a drug reaction in the erythema multiforme group. These are uncommon reactions to medications, with an incidence of 0.4 to 1.2 per million person-years for toxic epidermal necrolysis and 1.2 to 6.0 per million person-years for Stevens–Johnson syndrome. The primary skin lesions are large erythemas, most often irregularly distributed and of a characteristic purplish-livid color, at times with flaccid blisters.
In dermatology, erythema multiforme major is a form of rash with skin loss or epidermal detachment.
Yuan-Tsong Chen is a Taiwanese geneticist and physician, notable for his work on human genetic disorders. He is the director emeritus (2001–2010) and distinguished research fellow (2001–present) of the Institute of Biomedical Sciences, Academia Sinica, Taiwan, and also tenured professor of pediatrics of Duke University (1993–present) Chen was a 2019 awardee of Taiwan's Presidential Science Award, as were Yuan-Pern Lee and Wei Fu-chan.
Severe cutaneous adverse reactions are a group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose, mouth, and lips. In more severe cases, SCARs also involves serious damage to internal organs. SCARs includes five syndromes: Drug reaction with eosinophilia and systemic symptoms ; Stevens–Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN), Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN); and Acute generalized exanthematous pustulosis (AGEP). The five disorders have similar pathophysiologies, i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop the SCARs-inducing effects of specific drugs and thereby avoid treatment with them. Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares a similar pathophysiology with SCARs and is caused by some of the same drugs which cause SCARs.
The p-i concept refers to the pharmacological interaction of drugs with immune receptors. It explains a form of drug hypersensitivity, namely T cell stimulation, which can lead to various acute inflammatory manifestations such as exanthems, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal nercrolysis, and complications upon withdrawing the drug.