HLA-A1

monoisoform
isoformgroup = HLA-A1
polymer_type = MHC Class I, A cell surface antigen


image_source = Rendering of PDB2|1W72: α (A*0101 gene product), β₂-microglobulin, and MAGE-1 peptide.
protein_type = transmembrane receptor/ligand
structure = αβ heterodimer
subunit_genes = HLA-A*01--, β₂-microglobulin
alias = HL-A1
linkout = HAwA
isoformCount = 1
subunit1 = allele
nick1 = A1
allele1a = 0101
images1 = PDB2|1W72
rareIsoforms = 2
rnick1 = A1.2
rallele1a = 0102
rnick2 = A1.3
rallele2a = 0103

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 .cite journal |author=Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF |title=The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin |journal=Tissue Antigens |volume=11 |issue=2 |pages=96–112 |year=1978 |month=February |pmid=77067 |doi= |url=] This group currently is dominated by A*0101. 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.

erotype

Serotype
color1=#B0E0FF |color2=#E0F0FF | color3 = #F0F8FF
gene = A
type = 1
types = 1
allelegroup = 01
alleles = 3
allele1 = 01 |type1alle1freq = 99 |N1 = 5612
allele2 = 02 |type1alle2freq = 95 |N2 = 129
allele3 = 03 |type1alle3freq = 78 |N3 = 9

In all instances so far, HLA-A1 has been found to be linked to disease by association, but there are few that define HLA-A1 has a predominant genetic risk relative to other gene-alleles in the vicinity of the A1 gene on the larger haplotype.

A1 and autoimmune diseases

A1 serotype was associated with a number of diseases as "HL-A"' antigens were first being described. The associations rapidly expanded to include 'HL-A8' HLA-B8, as the HLA A1 and B8 were found to be commonly linked. As DRw3 was characterized, autoimmune risk drifted toward the class II region. A1-B58 haplotype (A1-B17 where B58 is dominant) may remain associated with antineutrophil cytoplasmic antibodies (ANCA) [cite journal | author = Shankarkumar U, Ghosh K, Pradhan V, Badakere S, Mohanty D | title = Immunogenetic association in patients with antineutrophil cytoplasmic antibodies (ANCA) from Mumbai, Maharashtra, India. | journal = J Autoimmun | volume = 24 | issue = 3 | pages = 227–33 | year = 2005 | pmid = 15848045 | doi = 10.1016/j.jaut.2005.01.009]

A1 in diabetes

With the exception of type 1 diabetes, most of the evidence for direct association of A1 with autoimmune diseases evaporated as DR3 and DQ2 genes were characterized. While type 1 diabetes shows an extended association on the HLA A1-B8-DR3-DQ2 haplotype, the association appears not to extend beyond the HLA-B locus.cite journal |author=Noble JA, Martin A, Valdes AM, "et al" |title=Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls |journal=Hum. Immunol. |volume=69 |issue=4-5 |pages=291–300 |year=2008 |pmid=18486765 |pmc=2505335 |doi=10.1016/j.humimm.2008.02.003 |url=] A recent study of DR3-DQ2/DR4-DQ8 phenotype found that A1-cw7-B8 was actually lower than expected relative to other A-B types, indicating that risk associated genes are located between B8 and DR3. However a study elsewhere showed that A*0101 appears to alter risk for type 1 diabetes but not Cw7-B8.cite journal | author = Noble J, Valdes A, Bugawan T, Apple R, Thomson G, Erlich H | title = The HLA class I A locus affects susceptibility to type 1 diabetes. | journal = Hum Immunol | volume = 63 | issue = 8 | pages = 657–64 | year = 2002 | pmid = 12121673 | doi = 10.1016/S0198-8859(02)00421-4] The type 1 diabetes example shows the inherent difficulty in the use of linkage analysis alone to cipher risk.

A1 and allergic disease, sensitivities

Early in the study of HLA an association was found between HL A1,B8 in allergic disease, these are found to link to extended HLA A1-B8 region.

Oddly, A1 was also found associated with methotrexate-induced liver cirrhosis.cite journal |author=Zachariae H, Kragballe K, Thestrup-Pedersen K, Kissmeyer-Nielsen F |title=HLA antigens in methotrexate-induced liver cirrhosis |journal=Acta Derm. Venereol. |volume=60 |issue=2 |pages=165–66 |year=1980 |pmid=6155028 |doi= |url=] Whereas A1 was found negatively associated with other disease such as coal workers pneumoconiosis and leprosy.cite journal |author=Wagner MM, Darke C |title=HLA-A and B antigen frequencies in Welsh coalworkers with pneumoconiosis and Caplan's syndrome |journal=Tissue Antigens |volume=14 |issue=2 |pages=165–8 |year=1979 |month=August |pmid=91226 |doi= |url=] cite journal |author=Heise ER, Mentnech MS, Olenchock SA, "et al" |title=HLA-A1 and coalworkers' pneumoconiosis |journal=Am. Rev. Respir. Dis. |volume=119 |issue=6 |pages=903–8 |year=1979 |month=June |pmid=453710 |doi= |url=] cite journal |author=Shankarkumar U, Ghosh K, Badakere S, Mohanty D |title=Novel HLA Class I Alleles Associated with Indian Leprosy Patients |journal=J. Biomed. Biotechnol. |volume=2003 |issue=3 |pages=208–211 |year=2003 |pmid=12975536 |pmc=400212 |doi=10.1155/S1110724303210019 |url=]

A1 and infectious disease

Within the early studies, A1 was found associate with or protected against some infectious diseases.cite journal |author=Russell AS, Schlaut J |title=HL-A transplantation antigens in subjects susceptible to recrudescent herpes labialis |journal=Tissue Antigens |volume=6 |issue=4 |pages=257–61 |year=1975 |month=October |pmid=1198581 |doi= |url=] cite journal |author=Heise ER, Major PC, Mentnech MS, Parrish EJ, Jordon AL, Morgan WK |title=Predominance of histocompatibility antigens W18 and HL-A1 in miners resistant to complicated coalworkers pneumoconiosis |journal=Inhaled Part |volume=4 Pt 2 |issue= |pages=495–507 |year=1975 |month=September |pmid=1236236 |doi= |url=] cite journal |author=Hug G |title=Genetic factors and autoimmunity in viral hepatitis |journal=Am. J. Clin. Pathol. |volume=65 |issue=5 Suppl |pages=870–5 |year=1976 |month=May |pmid=218441 |doi= |url=] Some diseases found associated with A1 actually link to the extended A1-B8 haplotype, viral induced hepatitis and accelerated progression of HIV are examples.

A1 with B8 showed an increase risk of measles infection,cite journal |author=Honeyman MC, Dorman DC, Menser MA, Forrest JM, Guinan JJ, Clark P |title=HL-A antigens in congenital rubella and the role of antigens 1 and 8 in the epidemiology of natural rubella |journal=Tissue Antigens |volume=5 |issue=1 |pages=12–8 |year=1975 |month=February |pmid=1138435 |doi= |url=] however, the significance was not consistent.cite journal |author=Harcourt GC, Best JM, Banatvala JE, Kennedy LA |title=HLA antigens and responses to rubella vaccination |journal=J Hyg (Lond) |volume=83 |issue=3 |pages=405–12 |year=1979 |month=December |pmid=512353 |doi= |url=] A more recent paper showed an association of A*0101 with lower than average responses to measles vaccine.cite journal |author=Ovsyannikova IG, Ryan JE, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA |title=Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses |journal=Immunogenetics |volume=57 |issue=11 |pages=828–36 |year=2005 |month=December |pmid=16331510 |doi=10.1007/s00251-005-0061-6 |url=] With rubella, A1-B8 was more frequently found in people infected as a result of maternal transefance.cite journal |author=Forrest JM, Turnbull FM, Sholler GF, "et al" |title=Gregg's congenital rubella patients 60 years later |journal=Med. J. Aust. |volume=177 |issue=11-12 |pages=664–7 |year=2002 |pmid=12463994 |doi= |url=http://www.mja.com.au/public/issues/177_11_021202/for10634_fm.html] A1 was also found to associate with circumoral herpes.cite journal |author=Russell AS, Schlaut J |title=HL-A transplantation antigens in subjects susceptible to recrudescent herpes labialis |journal=Tissue Antigens |volume=6 |issue=4 |pages=257–61 |year=1975 |month=October |pmid=1198581 |doi= |url=] An association between A1 and cold sores was also described.cite journal |author=Russell AS, Schlaut J |title=Association of HLA-A1 antigen and susceptibility to recurrent cold sores |journal=Arch Dermatol |volume=113 |issue=12 |pages=1721–2 |year=1977 |month=December |pmid=596908 |doi= |url=] Subsequently, the association for herpes simplex was also shown.cite journal |author=Jabbar AA, al-Samarai AM, al-Amar NS |title=HLA antigens associated with susceptibility to herpes simplex virus infection |journal=Dis. Markers |volume=9 |issue=5 |pages=281–7 |year=1991 |pmid=1797451 |doi= |url=]

A1 in Lymphoma

In Hodgkin's lymphoma HLA-A1cite journal |author=Hors J, Dausset J |title=HLA and susceptibility to Hodgkin's disease |journal=Immunol. Rev. |volume=70 |issue= |pages=167–92 |year=1983 |pmid=6403456 |doi= |url=] , but DR3 was not found higher.cite journal |author=Hansen JA, Young CW, Whitsett C, "et al" |title=HLA and MLC typing in patients with Hodgkin's disease |journal=Prog. Clin. Biol. Res. |volume=16 |issue= |pages=217–27 |year=1977 |pmid=143667 |doi= |url=] The A1-B8-DR3-DQ2 haplotype has a known association with Enteropathy-associated T-cell lymphoma, approximately 70% of patients are homozygotes for DQ2 with at least one copy of DR3-DQ2.

Alleles

AlleleFreq
Placement = right
Allele = A*0101
Freq1 = 25.0 | People1 = Ireland South
Freq2 = 21.5 | People2 = England Lancaster
Freq3 = 21.1 | People3 = Wales
Freq4 = 20.2 | People4 = Ireland Northern
Freq5 = 19.7 | People5 = England Sheffield
Freq6 = 19.4 | People6 = England Liverpool
Freq7 = 19.3 | People7 = England Newcastle
Freq8 = 19.2 | People8 = Spain Basque Arratia Vall…
Freq9 = 19.1 | People9 = England Leeds
Freq10 = 18.9 | People10 = England Manchester
Freq11 = 18.7 | People11 = Australia New South Wales
Freq12 = 18.5 | People12 = Australia West
Freq13 = 17.0 | People13 = Scotland Orkney
Freq14 = 17.0 | People14 = South Africa Natal Tamil
Freq15 = 15.5 | People15 = Belgium
Freq16 = 15.4 | People16 = Italy North (1)
Freq17 = 15.2 | People17 = Israeli Jews
Freq18 = 15.0 | People18 = France South East
Freq19 = 14.4 | People19 = German Essen
Freq20 = 14.0 | People20 = Russia Arkhangelsk Pomors
Freq21 = 13.7 | People21 = Nador Metalsa (Berber)
Freq22 = 13.6 | People22 = Sweden Stockholm
Freq23 = 13.5 | People23 = Spain Basque Gipuzkoa Pro…
Freq24 = 13.3 | People24 = Burkina Faso Fulani
Freq25 = 13.3 | People25 = Pakistan Sindhi
Freq26 = 13.2 | People26 = Serbia
Freq27 = 13.0 | People27 = Portugal Centre
Freq28 = 13.0 | People28 = Sweden Uppsala County
Freq29 = 12.7 | People29 = Czech Republic
Freq30 = 12.5 | People30 = India Andhra Pradesh Goll…
Freq31 = 12.4 | People31 = Israel Gaza Palestinians
Freq32 = 12.3 | People32 = India Mumbai Marathas
Freq33 = 12.3 | People33 = Tunisia
Freq34 = 12.3 | People34 = Algeria1
Freq35 = 12.2 | People35 = Romanian
Freq36 = 12.1 | People36 = Italy
Freq37 = 11.9 | People37 = Russia Northwest
Freq38 = 11.8 | People38 = Kenya Nandi
Freq39 = 11.4 | People39 = Spain Eastern Andalusia
Freq40 = 11.3 | People40 = Macedonia (4)
Freq41 = 11.2 | People41 = Tunisia
Freq42 = 10.9 | People42 = Turkey (I)
Freq43 = 10.8 | People43 = Spain North Cantabrian
Freq44 = 10.0 | People44 = Greece North
Freq45 = 9.7 | People45 = Croatia
Freq46 = 9.7 | People46 = Italy South Campania
Freq47 = 9.2 | People47 = Greece (3)
Freq48 = 9.1 | People48 = Brazil
Freq49 = 8.9 | People49 = Finland
Freq50 = 8.7 | People50 = Saudi Arabia
Freq51 = 8.6 | People51 = Spain Catalonia Girona
Freq52 = 8.3 | People52 = Pakistan Karachi Parsi
Freq53 = 8.3 | People53 = Uganda Kampala
Freq54 = 8.0 | People54 = Mongolia Khalkha
Freq55 = 7.9 | People55 = Jordan Amman
Freq56 = 7.6 | People56 = Spain North Cabuernigo
Freq57 = 7.4 | People57 = Kenya Luo
Freq58 = 7.3 | People58 = Bulgaria
Freq59 = 7.3 | People59 = Russia Chuvash
Freq60 = 7.2 | People60 = Oman
Freq61 = 7.0 | People61 = Singapore Javanese Indone…
Freq62 = 6.7 | People62 = Georgia Tibilisi Kurds
Freq63 = 6.5 | People63 = France Corsica
Freq64 = 5.7 | People64 = Georgia Tibilisi Georgian…
Freq65 = 5.6 | People65 = Georgia Svaneti Svans
Freq66 = 5.5 | People66 = China Qinghai Hui
Freq67 = 5.3 | People67 = Australian Aborigine Cape…
Freq68 = 5.0 | People68 = Sudanese
Freq69 = 4.5 | People69 = Italy Sardinia(3)
Freq70 = 4.0 | People70 = Russia Murmansk Saomi
Freq71 = 3.8 | People71 = Spain Pas Valley
Freq72 = 3.5 | People72 = Zambia Lusaka
Freq73 = 3.2 | People73 = Burkina Faso Rimaibe
Freq74 = 3.2 | People74 = Singapore Riau Malay
Freq75 = 3.1 | People75 = Kenya
Freq76 = 3.1 | People76 = Russia Nenets
Freq77 = 3.0 | People77 = Cameroon Bakola Pygmy
Freq78 = 2.8 | People78 = Thailand
Freq79 = 2.7 | People79 = Australian Aborigine Groo…
Freq80 = 2.7 | People80 = Senegal Niokholo Mandenka
Freq81 = 2.6 | People81 = Cameroon Bamileke
Freq82 = 2.5 | People82 = India Jalpaiguri Toto
Freq83 = 2.4 | People83 = China Shanghai
Freq84 = 2.4 | People84 = Thailand Northeast AlleleFreq
Placement = left
Allele = A*0102
Freq1 = 3.3 | People1 = India North Delhi
Freq2 = 2.7 | People2 = Kenya Nandi
Freq3 = 1.6 | People3 = Cape Verde Southeastern I…
Freq4 = 1.6 | People4 = Senegal Niokholo Mandenka
Freq5 = 1.1 | People5 = Mali Bandiagara
Freq6 = 1.0 | People6 = Tunisia
Freq7 = 0.8 | People7 = Guinea Bissau
Freq8 = 0.8 | People8 = Madeira
Freq9 = 0.7 | People9 = USA African Americans (3)
Freq10 = 0.6 | People10 = Argentina Toba Rosario
Freq11 = 0.6 | People11 = USA Hispanic
Freq12 = 0.4 | People12 = Kenya Luo
Freq13 = 0.3 | People13 = Cameroon Beti
Freq14 = 0.3 | People14 = Russia Tuva (2)
Freq15 = 0.3 | People15 = Uganda KampalaAlleleFreq
Placement = left
Allele = A*0103
Freq1 = 2.1 | People1 = Israel Ashkenazi and Non …
Freq2 = 1.7 | People2 = Kenya Nandi
Freq3 = 1.5 | People3 = Sudanese
Freq4 = 0.7 | People4 = Kenya
Freq5 = 0.7 | People5 = Saudi Arabia Guraiat and …
Freq6 = 0.6 | People6 = Iran Baloch
Freq7 = 0.5 | People7 = Ch. Guangdong Meizhou Han
Freq8 = 0.2 | People8 = China Beijing Shijiazhuan…

Most of the disease risk conferred by A*0101 are represented by either A1 serotype risks, or A1-B8 serotype risk (In Europe A1-B8 is almost always composed of A*0101 and B*0801). The other alleles, A*0102 and A*0103, may confer specific risks. For example, A*0102 was found linked to a type of stroke seen frequently in children with sickle cell anemia.cite journal |author=Hoppe C, Klitz W, Noble J, Vigil L, Vichinsky E, Styles L |title=Distinct HLA associations by stroke subtype in children with sickle cell anemia |journal=Blood |volume=101 |issue=7 |pages=2865–9 |year=2003 |month=April |pmid=12517810 |doi=10.1182/blood-2002-09-2791 |url=]

There is a report that the in the Somali communities within the US 2/3rds of A1 bearers have the A*0103 isoform.

A1-B haplotypes

*A1-B8 Western Irish, N. Irish, Scottish, Wales, NW England, Scandinavia, Yugoslavia, Russia,....
*A1-B7 Armenia, Austria, NW Europe (regional recombinant between A1-B8 and A2/A3-B7)
*A1-B13 Uralic
*A1-B35 (Albania, Belgium, Italy, Greece, France - Eastern mediterranian in origin)
*A1-B37 Yakuts, Tribal-India, Iyers-India, Mongolian, Indian, Orochon, Romanian, Yugoslavia, Korean, Albania, French, German, Manchu
*A1-B51 Yugoslavia, Germany, Iberia, Italy
*A1-B52 Bharghavas-India, Tribal-India, Italy, Iberia, France
*A1-B57 (See tables on discussion page)
*A1-B58 (See tables on discussion page)

References