HLA-B39 explained

HLA-B (alpha)-β2MG with bound peptide

major histocompatibility complex (human), class I, B39

Alleles B*3901, 3902, 3903, . .
Structure (See HLA-B)
Shared data
chr.6 6p21.31

HLA-B39 (B39) is an HLA-B serotype. The serotype identifies the more common HLA-B*39 gene products.[1]

B39 is a split antigen of the broad antigen B16, and is a sister type of B38. B39 is most commonly found on the west pacific rim, in Japan and highest frequency in the new world. In Europe it is found in Scandinavia and Northern Russia.

Serotype

Serotypes B39, B16, and B38 recognition of the
HLA B*39 gene products[2]
B*39 B39 B16 B38 Sample
allele % % % size (N)
3901 95 476
3902 87 96
3903 77 20
3905 82 245
3906 94 508
3908 48 57
3909 97 13
3910 82 127
3911 69 16
Alleles link-out to IMGT/HLA Databease at EBI

The serology for the most common B39 alleles, B*3901 and B*3906 is good, but some allele products are not well detected. Given the differential involvement of these alleles in disease testing should involve high resolution typing.

HLA B*3906 frequencies
freq
ref. Population (%)
[3] Venezuela Perja Mountain Bari23.9
Mexico Mixtec Oaxaca8.8
USA Arizona Pima7.3
USA South Texas Hispanics5.6
Mexico Zaptotec Oaxaca4.5
New Mexico Canoncito Navajo3.7
Oman2.5
PNG Wanigela2.3
Tunisia Tunis2.3
North American Natives1.9
USA Hispanic1.7
Brazil Belo Horizonte1.6
South Dakota Lakota Sioux1.5
Cuban White1.4
Azores S. Maria & S. Miguel1.3
Australia New South Wales1.1
Finland1.1
Portugal North1.1
Portugal Centre1.0
Spain Eastern Andalusia Gipsy1.0
Brazil Terena0.9
Ireland Northern0.9
Azores Terceira Island0.8
USA Caucasian pop20.8
Brazil0.7
USA Philadelphia Caucasians0.7
India Andhra Pradesh Golla0.5
Thailand0.4

Alleles

HLA B*3901 frequencies
freq
ref. Population (%)
Taiwan Saisiat54.9
Taiwan Tsou24.5
South Dakota Lakota Sioux22.5
Taiwan Taroko21.8
Taiwan Atayal19.8
PNG Wanigela16.7
Japan Ainu Hokkaido16.0
Taiwan Bunun14.9
New Mexico Canoncito Navajo14.6
Taiwan Thao13.3
Taiwan Rukai13.0
Taiwan Ami10.2
USA Hawaii Okinawa7.7
Papua New Guinea Wosera7.0
Papua New Guinea Madang6.4
Mexico Mixtec Oaxaca5.9
Taiwan Puyuma5.0
Taiwan Paiwan4.9
New Caledonia4.8
Japan Central4.4
American Samoa4.0
USA North American Natives4.0
Taiwan Hakka3.6
Indig. Australian Cape York Peninsula3.5
Japan (5)3.5
Philippines Ivatan3.0
Brazil2.9
China Guangxi Maonan2.8
Georgia Tbilisi Georgians2.8
China Yunnan Nu2.6
Thailand2.5
Azores Terceira Island2.4
Singapore Chinese2.4
Romanian2.3
China Yunnan Lisu2.2
Indig. Australian Yuendumu2.1
China Guangzhou2.0
Croatia2.0
France South East1.9
Georgia Svaneti Svans1.9
PNG Karimui Plateau1.9
Azores Central Islands1.8
Spain Eastern Andalusia1.8
Uganda Kampala1.6
Mexico Zaptotec Oaxaca1.5
Singapore Thai1.5
China Guangzhou Han1.4
China Qinghai Hui1.4
Czech Republic1.4
Madeira1.4
Indig. Australian Kimberly1.3
Finland1.1

Disease

B39 is suggested as a factor in Takayasu's arteritis and gallstones in Mexico.[4] Osteoarticular complications of brucellosis appear to be associated with B39.[5] An association with spondylarthropathies[6] [7] and psoriatic arthritis[8] [9] was observed in several studies. Psoriatic arthritis appears to be linked to MICA-A9 which tightly linked to HLA-B39.[10] [11] B39 also appears to be involved in the Fishers syndrome variant of Guillain–Barré syndrome.[12]

B39 appears to be protective against cardiomyopathy in Chaga's disease indicating a possible selective factor in its rise in the New World.[13] Chaga's disease is caused by a trypanosome carried by a blood sucking insect found in tropical, palm growing regions.

Southern California now reports cases of Chaga's disease from contaminated transfusions and may be already a habitat for the vector.[14]

In Takayasu's arteritis

Takayasu's arteritis appears to have a link to B39.[15] [16] The association with B*3902 increases risk of pulmonary infarction, ischemic heart disease, aortic regurgitation, systemic hypertension, renal artery stenosis, cerebrovascular disease, and visual disturbance.[17] B*3906, common in indigenous Mesoamericans has been found associated with the same disease.[18]

HLA B*3902 frequencies
freq
ref. Population (%)
Mexico Mixe Oaxaca38.7
Mexico Zaptotec Oaxaca13.4
Mexico Mixtec Oaxaca5.9
Mexico Mestizos1.2
Japan pop50.9
Cuban White0.7
Israel Ashk. and Non Ashk. Jews0.5
Japan Central0.5
Senegal Niokholo Mandenka0.5
B*3903
PNG New Britain Rabaul13.2
Brazil Terena11.2
Argentina Toba Rosario5.2
Brazil0.7
Finland0.6
Kenya Luo0.6
North American Natives0.5
B*3904
Argentina Toba Rosario1.2
Georgia Svaneti Svans0.6
Jordan Amman0.3
Shijiazhuang Tianjian Han0.1
Japan Central0.1
Romanian0.1
B*3905
Venezuela Perija Yucpa36.1
Mexico Zaptotec Oaxaca12.7
Mexico Mixtec Oaxaca9.8
Mexico Mestizos4.9
Arizona Pima4.5
Mexico Guadalajara Mestizos2.4
Argentina Toba Rosario2.3
USA Hispanic2.1
Mexico Mixe Oaxaca1.9
Cuban White1.4
Mexico Chihuahua Tarahumara1.1
USA North American Natives0.5
Shijiazhuang Tianjian Han0.2
B*3907
Shijiazhuang Tianjian Han0.6
Singapore Thai0.5
China South Han0.2
B*3908
Mexico Zaptotec Oaxaca2.2
Mexico Mestizos1.2
Mexico Mixtec Oaxaca1.0
Brazil0.7
USA Hispanic0.6
B*3909
Venezuela Perija Yucpa34.9
Thailand pop33.1
Brazil Terena1.7
China South Han1.4
Argentina Toba Rosario1.2
China Qinghai Hui0.9
B*3910
Sudanese2.5
Senegal Niokholo Mandenka2.1
South African Natal Zulu1.5
Cameroon Beti1.4
Spain Eastern Andalusia1.2
Kenya Luo1.1
Israel Arab Druse1.0
Kenya Nandi1.0
Guinea Bissau0.8
Kenya 0.7
Mali Bandiagara0.7
Morocco Nador Metalsa Class I0.7
Cameroon Bamileke0.6
Cameroon Yaounde0.5
Israel Ashk. and Non Ashk. Jews0.5
Saudi Arabia Guraiat and Hail0.5

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. http://www.ebi.ac.uk/imgt/hla/allele.html derived from IMGT/HLA
  3. 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 .
  4. Méndez-Sánchez N, King-Martínez AC, Ramos MH, Pichardo-Bahena R, Uribe M . The Amerindian's genes in the Mexican population are associated with development of gallstone disease . Am. J. Gastroenterol. . 99 . 11 . 2166–70 . November 2004 . 15554998 .
  5. Bravo MJ, Colmenero Jde D, Alonso A, Caballero A . HLA-B*39 allele confers susceptibility to osteoarticular complications in human brucellosis . J. Rheumatol. . 30 . 5 . 1051–3 . May 2003 . 12734905 .
  6. Sobao Y, Tsuchiya N, Takiguchi M, Tokunaga K . Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies . Arthritis Rheum. . 42 . 1 . 175–81 . January 1999 . 9920028 . 10.1002/1529-0131(199901)42:1<175::AID-ANR21>3.0.CO;2-7 . free .
  7. Alvarez I, López de Castro JA . HLA-B27 and immunogenetics of spondyloarthropathies . Curr Opin Rheumatol . 12 . 4 . 248–53 . July 2000 . 10910175 . 10.1097/00002281-200007000-00003.
  8. Eastmond CJ . Psoriatic arthritis. Genetics and HLA antigens . Baillière's Clinical Rheumatology . 8 . 2 . 263–76 . May 1994 . 8076387 . 10.1016/S0950-3579(94)80018-9.
  9. Gladman DD, Farewell VT . The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Multivariate relative risk model . Arthritis Rheum. . 38 . 6 . 845–50 . June 1995 . 7779129 . 10.1002/art.1780380619. free .
  10. Bolognesi E, Dalfonso S, Rolando V, Fasano ME, Praticò L, Momigliano-Richiardi P . MICA and MICB microsatellite alleles in HLA extended haplotypes . Eur. J. Immunogenet. . 28 . 5 . 523–30 . October 2001 . 11881819 . 10.1046/j.0960-7420.2001.00250.x .
  11. González S, Martínez-Borra J, López-Vázquez A, García-Fernández S, Torre-Alonso JC, López-Larrea C . MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis . J. Rheumatol. . 29 . 5 . 973–8 . May 2002 . 12022360 . 2008-08-03 . https://web.archive.org/web/20081204132408/http://www.jrheum.com/subscribers/02/05/973.html . 2008-12-04 . dead .
  12. Yuki N, Sato S, Tsuji S, Ogawa K, Miyatake T . Human leukocyte antigens in Fisher's syndrome . Ann. Neurol. . 33 . 6 . 655–7 . June 1993 . 8498847 . 10.1002/ana.410330617 .
  13. Cruz-Robles D, Reyes PA, Monteón-Padilla VM, Ortiz-Muñiz AR, Vargas-Alarcón G . MHC class I and class II genes in Mexican patients with Chagas disease . Hum. Immunol. . 65 . 1 . 60–5 . January 2004 . 14700597 . 10.1016/j.humimm.2003.10.008.
  14. Web site: Chagas Disease Represents New Challenge for Blood Supply Safety.
  15. Kimura A, Kitamura H, Date Y, Numano F . Comprehensive analysis of HLA genes in Takayasu arteritis in Japan . Int. J. Cardiol. . 54 Suppl . S61–9 . August 1996 . 9119528 . 10.1016/s0167-5273(96)88774-2.
  16. Yoshida M, Kimura A, Katsuragi K, Numano F, Sasazuki T . DNA typing of HLA-B gene in Takayasu's arteritis . Tissue Antigens . 42 . 2 . 87–90 . August 1993 . 7903491 . 10.1111/j.1399-0039.1993.tb02242.x.
  17. Kitamura H, Kobayashi Y, Kimura A, Numano F . Association of clinical manifestations with HLA-B alleles in Takayasu arteritis . Int. J. Cardiol. . 66 Suppl 1 . S121–6 . October 1998 . 9951811 . 10.1016/S0167-5273(98)00159-4.
  18. Rodríguez-Reyna TS, Zúñiga-Ramos J, Salgado N, etal . Intron 2 and exon 3 sequences may be involved in the susceptibility to develop Takayasu arteritis . Int. J. Cardiol. . 66 Suppl 1 . S135–8; discussion S139 . October 1998 . 9951813 . 10.1016/S0167-5273(98)00161-2.