HLA-B57 explained

HLA-B (alpha)-β2MG with bound peptide

major histocompatibility complex (human), class I, B57

Alleles
  • 5701, *5702, *5703, *5704, *5708[1]
Structure (See HLA-B)
Shared data
chr.6 6p21.31

HLA-B57 (B57) is an HLA-B serotype. B57 is a split antigen from the B17 broad antigen, the sister serotype being B58.[2] The serotype identifies the more common HLA-B*57 gene products.[1] (For terminology help see: HLA-serotype tutorial.) Like B58, B57 is involved in drug-induced inflammatory skin disorders.

Disease

HLA-B*5701 is associated with drug-induced inflammatory disease of the skin. Individuals with B57 are more sensitive to the drug abacavir.[3] Abacavir is an antiretroviral drug used in treatment of HIV, however in sensitive individuals fever, skin rash, fatigue, gastrointestinal symptoms such as nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea, or cough can develop. FDA has advised that people from at-risk ethnic groups, (see alle distribution table) be screened prior to drug-therapy.[4] [Note: phenotype frequencies are roughly double allele frequencies -tabled values- when allele frequency is less than 30%]

The mechanism by which abacavir causes this type 4 hypersensitivity reaction is by binding in the antigen-binding cleft of the HLA-B*57:01 protein, allowing new, "non-self" antigens to bind and be presented to T cells.[5]

Serotype

B57 and B17 serotype recognition of some more common HLA B*57 alleles[6]
B*57 B57 B17 Sample
allele % % size (N)
5701 92 5 3670
5702 78 8 65
5703 85 6 412
5704 67 7 32

Allele distribution

HLA B*5701 frequencies
freq
ref. Population (%)
[7] South Africa Natal Tamil10.2
India Tamil Nadu Nadar8.2
Spain E. Andalusia Gipsy7.1
Ireland South5.8
India North Delhi4.9
India New Delhi3.8
Ireland Northern3.8
Azores Central Islands3.6
Cuban White3.6
France South East3.5
China Guangzhou Han3.3
China North Han3.3
Czech Republic3.3
Russia Tuva (2)3.3
Cape Verde NW Islands3.2
Azores Terceira Island3.1
Portugal South3.1
Thailand (3)3.1
Uganda Kampala3.1
Portugal Centre3.0
Tunisia3.0
India Andhra Pradesh Golla2.9
Belgium2.0
China Inner Mongolia2.0
Croatia2.0
SP Javanese Indonesians2.0
Singapore Riau Malay2.0
India North Hindus1.9
Bulgaria1.8
Thailand1.8
Finland1.7
Macedonia pop 41.6
Madeira1.6
Indig. Australian Cape York Penin.1.5
Israel Arab Druse1.5
Sudanese1.5
Morocco Nador Metalsa (Berber)1.4
Oman1.3
Mexico Mestizos1.2
Zambia Lusaka1.1
Shijiazhuang Tianjian Han1.0
Iran Baloch1.0
USA Asian1.0
HLA B*5702 frequencies
freq
ref. Population (%)
Zambia Lusaka2.3
Senegal Niokholo Mandenka1.6
Kenya 1.4
Mali Bandiagara1.1
South African Natal Zulu1.0
B*5703
Zambia Lusaka5.7
Cameroon Bakola Pygmy5.0
Ivory Coast Akan Adiopodoume4.6
Zimbabwe Harare Shona4.4
South African Natal Zulu4.0
Cameroon Bamileke3.2
Cameroon Beti3.2
Kenya Nandi2.9
Israel Ashk. & Non-Ashk. Jews2.8
Cameroon Yaounde2.7
Tunisia Tunis2.3
Saudi Arabia Guraiat and Hail1.5

Notes and References

  1. 2848993 . 2010 . Marsh . S. G. . Nomenclature for factors of the HLA system, 2010 . Tissue Antigens . 75 . 4 . 291–455 . Albert . E. D. . Bodmer . W. F. . Bontrop . R. E. . Dupont . B. . Erlich . H. A. . Fernández-Viña . M. . Geraghty . D. E. . Holdsworth . R. . Hurley . C. K. . Lau . M. . Lee . K. W. . Mach . B. . Maiers . M. . Mayr . W. R. . Müller . C. R. . Parham . P. . Petersdorf . E. W. . Sasazuki . T. . Strominger . J. L. . Svejgaard . A. . Terasaki . P. I. . Tiercy . J. M. . Trowsdale . J. . 20356336 . 10.1111/j.1399-0039.2010.01466.x .
  2. Ways JP, Coppin HL, Parham P . The complete primary structure of HLA-Bw58 . J. Biol. Chem. . 260 . 22 . 11924–33 . 1985 . 10.1016/S0021-9258(17)38967-6 . 2995352 . free .
  3. Chung WH, Hung SI, Chen YT . Human leukocyte antigens and drug hypersensitivity . Curr Opin Allergy Clin Immunol . 7 . 4 . 317–23 . August 2007 . 17620823 . 10.1097/ACI.0b013e3282370c5f . 31415054 .
  4. https://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm FDA abacavir alert web access July 29, 2008
  5. Illing. Patricia T.. Vivian. Julian P.. Dudek. Nadine L.. Kostenko. Lyudmila. Chen. Zhenjun. Bharadwaj. Mandvi. Miles. John J.. Kjer-Nielsen. Lars. Gras. Stephanie. Williamson. Nicholas A.. Burrows. Scott R.. 2012-06-28. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. en. 486. 7404. 554–558. 10.1038/nature11147. 22722860 . 4408811 . 0028-0836. free. 2012Natur.486..554I .
  6. http://www.ebi.ac.uk/imgt/hla/allele.html derived from IMGT/HLA
  7. Middleton D, Menchaca L, Rood H, Komerofsky R . New allele frequency database . Tissue Antigens . 61 . 5 . 403–7 . 2003 . 12753660 . 10.1034/j.1399-0039.2003.00062.x . free .