HLA-A1
| HLA-A1 (MHC Class I, A cell surface antigen) | |||
 | |||
| Rendering of 1W72: α (A*0101 gene product), β2-microglobulin, and MAGE-1 peptide. | |||
| - | |||
| Protein | transmembrane receptor/ligand | ||
| Structure | αβ heterodimer | ||
| Subunits | HLA-A*01--, β2-microglobulin | ||
| Older names | "HL-A1" | ||
| - | |||
| subtype | allele | Available structures | |
| A1 | *0101 | 1W72 | |
| rare alleles | |||
| A1.2 | *0102 | ||
| A1.3 | *0103 | ||
| Alleles link-out to IMGT/HLA database at EBI | |||
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.[1] 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.
Serotype
| A*01 | A1 | Sample |
| allele | % | size (N) |
| *0101 | 99 | 5612 |
| *0102 | 95 | 129 |
| *0103 | 78 | 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 anti-neutrophil cytoplasmic antibody (ANCA)[3]
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.[4] 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.[5] 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.[6] Whereas A1 was found negatively associated with other disease such as coal workers pneumoconiosis and leprosy.[7][8][9]
A1 and infectious disease
Within the early studies, A1 was found associate with or protected against some infectious diseases.[10][11][12] 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,[13] however, the significance was not consistent.[14] A more recent paper showed an association of A*0101 with lower than average responses to measles vaccine.[15] With rubella, A1-B8 was more frequently found in people infected as a result of maternal transefance.[16] A1 was also found to associate with circumoral herpes.[10] An association between A1 and cold sores was also described.[17] Subsequently, the association for herpes simplex was also shown.[18]
A1 in Lymphoma
In Hodgkin's lymphoma HLA-A1,[19] but DR3 was not found higher.[20] 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
| Study population |
Freq. (in %)[21] |
|---|---|
| Ireland South | 25.0 |
| England Lancaster | 21.5 |
| Wales | 21.1 |
| Ireland Northern | 20.2 |
| England Sheffield | 19.7 |
| England Liverpool | 19.4 |
| England Newcastle | 19.3 |
| Spain Basque Arratia Vall… | 19.2 |
| England Leeds | 19.1 |
| England Manchester | 18.9 |
| Australia New South Wales | 18.7 |
| Australia West | 18.5 |
| Scotland Orkney | 17.0 |
| South Africa Natal Tamil | 17.0 |
| Belgium | 15.5 |
| Italy North (1) | 15.4 |
| Israeli Jews | 15.2 |
| France South East | 15.0 |
| German Essen | 14.4 |
| Russia Arkhangelsk Pomors | 14.0 |
| Nador Metalsa (Berber) | 13.7 |
| Sweden Stockholm | 13.6 |
| Spain Basque Gipuzkoa Pro… | 13.5 |
| Burkina Faso Fulani | 13.3 |
| Pakistan Sindhi | 13.3 |
| Serbia | 13.2 |
| Portugal Centre | 13.0 |
| Sweden Uppsala County | 13.0 |
| Czech Republic | 12.7 |
| India Andhra Pradesh Goll… | 12.5 |
| Israel Gaza Palestinians | 12.4 |
| India Mumbai Marathas | 12.3 |
| Tunisia | 12.3 |
| Algeria1 | 12.3 |
| Romanian | 12.2 |
| Italy | 12.1 |
| Russia Northwest | 11.9 |
| Kenya Nandi | 11.8 |
| Spain Eastern Andalusia | 11.4 |
| Macedonia (4) | 11.3 |
| Tunisia | 11.2 |
| Turkey (I) | 10.9 |
| Spain North Cantabrian | 10.8 |
| Greece North | 10.0 |
| Croatia | 9.7 |
| Italy South Campania | 9.7 |
| Greece (3) | 9.2 |
| Brazil | 9.1 |
| Finland | 8.9 |
| Saudi Arabia | 8.7 |
| Spain Catalonia Girona | 8.6 |
| Pakistan Karachi Parsi | 8.3 |
| Uganda Kampala | 8.3 |
| Mongolia Khalkha | 8.0 |
| Jordan Amman | 7.9 |
| Spain North Cabuernigo | 7.6 |
| Kenya Luo | 7.4 |
| Bulgaria | 7.3 |
| Russia Chuvash | 7.3 |
| Oman | 7.2 |
| Singapore Javanese Indone… | 7.0 |
| Georgia Tibilisi Kurds | 6.7 |
| France Corsica | 6.5 |
| Georgia Tibilisi Georgian… | 5.7 |
| Georgia Svaneti Svans | 5.6 |
| China Qinghai Hui | 5.5 |
| Australian Aborigine Cape… | 5.3 |
| Sudanese | 5.0 |
| Italy Sardinia(3) | 4.5 |
| Russia Murmansk Saomi | 4.0 |
| Spain Pas Valley | 3.8 |
| Zambia Lusaka | 3.5 |
| Burkina Faso Rimaibe | 3.2 |
| Singapore Riau Malay | 3.2 |
| Kenya | 3.1 |
| Russia Nenets | 3.1 |
| Cameroon Bakola Pygmy | 3.0 |
| Thailand | 2.8 |
| Australian Aborigine Groo… | 2.7 |
| Senegal Niokholo Mandenka | 2.7 |
| Cameroon Bamileke | 2.6 |
| India Jalpaiguri Toto | 2.5 |
| China Shanghai | 2.4 |
| Thailand Northeast | 2.4 |
| Allele frequencies presented, only | |
| Study population |
Freq. (in %)[21] |
|---|---|
| India North Delhi | 3.3 |
| Kenya Nandi | 2.7 |
| Cape Verde Southeastern I… | 1.6 |
| Senegal Niokholo Mandenka | 1.6 |
| Mali Bandiagara | 1.1 |
| Tunisia | 1.0 |
| Guinea Bissau | 0.8 |
| Madeira | 0.8 |
| USA African Americans (3) | 0.7 |
| Argentina Toba Rosario | 0.6 |
| USA Hispanic | 0.6 |
| Kenya Luo | 0.4 |
| Cameroon Beti | 0.3 |
| Russia Tuva (2) | 0.3 |
| Uganda Kampala | 0.3 |
| Allele frequencies presented, only | |
| Study population |
Freq. (in %)[21] |
|---|---|
| Israel Ashkenazi and Non … | 2.1 |
| Kenya Nandi | 1.7 |
| Sudanese | 1.5 |
| Kenya | 0.7 |
| Saudi Arabia Guraiat and … | 0.7 |
| Iran Baloch | 0.6 |
| Ch. Guangdong Meizhou Han | 0.5 |
| China Beijing Shijiazhuan… | 0.2 |
| Allele frequencies presented, only | |
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.[22]
There is a report that in the Somali communities within the US 2/3 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 Mediterranean 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
- ↑ Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF (February 1978). "The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin". Tissue Antigens. 11 (2): 96–112. doi:10.1111/j.1399-0039.1978.tb01233.x. PMID 77067.
- ↑ Allele Query Form IMGT/HLA - European Bioinformatics Institute
- ↑ Shankarkumar U, Ghosh K, Pradhan V, Badakere S, Mohanty D (2005). "Immunogenetic association in patients with antineutrophil cytoplasmic antibodies (ANCA) from Mumbai, Maharashtra, India.". J Autoimmun. 24 (3): 227–33. doi:10.1016/j.jaut.2005.01.009. PMID 15848045.
- ↑ Noble JA, Martin A, Valdes AM, et al. (2008). "Type 1 diabetes risk for HLA-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3 and DR4 matched Italian patients and controls". Hum. Immunol. 69 (4–5): 291–300. doi:10.1016/j.humimm.2008.02.003. PMC 2505335
. PMID 18486765. - ↑ Noble J, Valdes A, Bugawan T, Apple R, Thomson G, Erlich H (2002). "The HLA class I A locus affects susceptibility to type 1 diabetes". Hum Immunol. 63 (8): 657–64. doi:10.1016/S0198-8859(02)00421-4. PMID 12121673.
- ↑ Zachariae H, Kragballe K, Thestrup-Pedersen K, Kissmeyer-Nielsen F (1980). "HLA antigens in methotrexate-induced liver cirrhosis". Acta Derm. Venereol. 60 (2): 165–66. PMID 6155028.
- ↑ Wagner MM, Darke C (August 1979). "HLA-A and B antigen frequencies in Welsh coalworkers with pneumoconiosis and Caplan's syndrome". Tissue Antigens. 14 (2): 165–8. doi:10.1111/j.1399-0039.1979.tb00834.x. PMID 91226.
- ↑ Heise ER, Mentnech MS, Olenchock SA, et al. (June 1979). "HLA-A1 and coalworkers' pneumoconiosis". Am. Rev. Respir. Dis. 119 (6): 903–8. PMID 453710.
- ↑ Shankarkumar U, Ghosh K, Badakere S, Mohanty D (2003). "Novel HLA Class I Alleles Associated with Indian Leprosy Patients". J. Biomed. Biotechnol. 2003 (3): 208–211. doi:10.1155/S1110724303210019. PMC 400212. PMID 12975536.
- 1 2 Russell AS, Schlaut J (October 1975). "HL-A transplantation antigens in subjects susceptible to recrudescent herpes labialis". Tissue Antigens. 6 (4): 257–61. doi:10.1111/j.1399-0039.1975.tb00640.x. PMID 1198581.
- ↑ Heise ER, Major PC, Mentnech MS, Parrish EJ, Jordon AL, Morgan WK (September 1975). "Predominance of histocompatibility antigens W18 and HL-A1 in miners resistant to complicated coalworkers pneumoconiosis". Inhaled Part. 4 Pt 2: 495–507. PMID 1236236.
- ↑ Hug G (May 1976). "Genetic factors and autoimmunity in viral hepatitis". Am. J. Clin. Pathol. 65 (5 Suppl): 870–5. PMID 218441.
- ↑ Honeyman MC, Dorman DC, Menser MA, Forrest JM, Guinan JJ, Clark P (February 1975). "HL-A antigens in congenital rubella and the role of antigens 1 and 8 in the epidemiology of natural rubella". Tissue Antigens. 5 (1): 12–8. doi:10.1111/j.1399-0039.1975.tb00520.x. PMID 1138435.
- ↑ Harcourt GC, Best JM, Banatvala JE, Kennedy LA (December 1979). "HLA antigens and responses to rubella vaccination". J Hyg (Lond). 83 (3): 405–12. doi:10.1017/S0022172400026231. PMC 2130160. PMID 512353.
- ↑ Ovsyannikova IG, Ryan JE, Vierkant RA, Pankratz VS, Jacobson RM, Poland GA (December 2005). "Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses". Immunogenetics. 57 (11): 828–36. doi:10.1007/s00251-005-0061-6. PMID 16331510.
- ↑ Forrest JM, Turnbull FM, Sholler GF, et al. (2002). "Gregg's congenital rubella patients 60 years later". Med. J. Aust. 177 (11–12): 664–7. PMID 12463994.
- ↑ Russell AS, Schlaut J (December 1977). "Association of HLA-A1 antigen and susceptibility to recurrent cold sores". Arch Dermatol. 113 (12): 1721–2. doi:10.1001/archderm.113.12.1721. PMID 596908.
- ↑ Jabbar AA, al-Samarai AM, al-Amar NS (1991). "HLA antigens associated with susceptibility to herpes simplex virus infection". Dis. Markers. 9 (5): 281–7. PMID 1797451.
- ↑ Hors J, Dausset J (1983). "HLA and susceptibility to Hodgkin's disease". Immunol. Rev. 70: 167–92. doi:10.1111/j.1600-065X.1983.tb00714.x. PMID 6403456.
- ↑ Hansen JA, Young CW, Whitsett C, et al. (1977). "HLA and MLC typing in patients with Hodgkin's disease". Prog. Clin. Biol. Res. 16: 217–27. PMID 143667.
- 1 2 3 Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660.
- ↑ Hoppe C, Klitz W, Noble J, Vigil L, Vichinsky E, Styles L (April 2003). "Distinct HLA associations by stroke subtype in children with sickle cell anemia". Blood. 101 (7): 2865–9. doi:10.1182/blood-2002-09-2791. PMID 12517810.