HLA-A1
Encyclopedia
HLA-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. 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.
. 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
)
Oddly, A1 was also found associated with methotrexate
-induced liver cirrhosis. Whereas A1 was found negatively associated with other disease such as coal workers pneumoconiosis
and leprosy.
A1 with B8 showed an increase risk of measles
infection, however, the significance was not consistent. A more recent paper showed an association of A*0101 with lower than average responses to measles vaccine
. With rubella, A1-B8 was more frequently found in people infected as a result of maternal transefance.
A1 was also found to associate with circumoral herpes. An association between A1 and cold sores was also described. Subsequently, the association for herpes simplex
was also shown.
, approximately 70% of patients are homozygotes for DQ2 with at least one copy of DR3-DQ2.
There is a report that the in the Somali communities within the US 2/3 of A1 bearers have the A*0103 isoform.
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
within HLA-A
HLA-A
HLA-A are a group of human leukocyte antigens that are encoded by the HLA-A locus on human chromosome 6p. The HLA genes constitute a large subset of the Major histocompatibility complex of humans. HLA-A is a component of certain MHC class I cell surface receptor isoforms that resides on the...
"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
B2M
B2M may refer to:*Boyz II Men, a singing group*Mitsubishi B2M, an aircraft*Back to Mine, a series of albums*Beta-2 microglobulin, a gene or protein*Business to machine, the practice of E-commerce where companies link directly to machines...
locus. 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
Haplotype
A haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...
that appears to have been frequent in the ancient peoples of Northwestern Europe. A1 is a frequent component of the AH8.1 haplotype
HLA A1-B8-DR3-DQ2
HLA A1-B8-DR3-DQ2 haplotype is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6...
.
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
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 describedHistory and naming of human leukocyte antigens
Human leukocyte antigens began as a list of antigens identified as a result of transplant rejection. The list, HL-A1 to HL-A15. The antigens were identified based on serotypes that developed in transplant recipients, to donor antigens that could recognize one apparent antigen were found useful....
. The associations rapidly expanded to include 'HL-A8' HLA-B8
HLA-B8
HLA-B8 is an HLA-B serotype. The serotype identifies the HLA-B*08 gene products. HLA-B8, previously known as HL-A8 was one of the first identified of the HLA antigens. It coined the "Super B8" haplotype, also called the ancestral European haplotype because of its common occurrence in Europe,...
, 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
ANCA
ANCA Pty Ltd is an Australia company which designs and manufactures CNC grinding machines. The company was founded in 1974 by Pat Boland and Pat McCluskey in Melbourne, Australia....
)
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. 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. 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
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
-induced liver cirrhosis. Whereas A1 was found negatively associated with other disease such as coal workers pneumoconiosis
Pneumoconiosis
Pneumoconiosis is an occupational lung disease and a restrictive lung disease caused by the inhalation of dust, often in mines.-Types:Depending upon the type of dust, the disease is given different names:...
and leprosy.
A1 and infectious disease
Within the early studies, A1 was found associate with or protected against some infectious diseases. 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
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
infection, however, the significance was not consistent. A more recent paper showed an association of A*0101 with lower than average responses to measles vaccine
MMR vaccine
The MMR vaccine is an immunization shot against measles, mumps, and rubella . It was first developed by Maurice Hilleman while at Merck in the late 1960s....
. With rubella, A1-B8 was more frequently found in people infected as a result of maternal transefance.
A1 was also found to associate with circumoral herpes. An association between A1 and cold sores was also described. Subsequently, the association for herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
was also shown.
A1 in Lymphoma
In Hodgkin's lymphoma HLA-A1, but DR3 was not found higher. The A1-B8-DR3-DQ2 haplotype has a known association with Enteropathy-associated T-cell lymphomaEnteropathy-Associated T-cell Lymphoma
Enteropathy-Associated T-cell Lymphoma , also enteropathy-type T-cell lymphoma , is a type of T-cell lymphoma that affects the small intestine. It is the most common primary gastrointestinal T-cell lymphoma, arising from the T cells that are found between the cells that line the small intestinal...
, approximately 70% of patients are homozygotes for DQ2 with at least one copy of DR3-DQ2.
Alleles
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.There is a report that the in the Somali communities within the US 2/3 of A1 bearers have the A*0103 isoform.
A1-B haplotypes
- A1-B8HLA A1-B8 haplotypeHLA A1-B8 is a multigene haplotype that covers the MHC Class I region of the human major histocompatibility complex on chromosome 6...
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)