HLA-DR1

Last updated
PBB Protein HLA-DRA image.jpg
DR1 binding pocket with ligand PDB: 2G9H ​ [1]
major histocompatibility complex, class II, DR1
Haplotypes groupsDRA*01:DRB1*0101 DRA*01:DRB1*0102 DRA*01:DRB1*0103
Structure (See HLA-DR)
Identifiers
alpha *0101
Symbol(s) HLA-DRA [ permanent dead link ]
EBI-HLA DRA *0101
Identifiers
beta 1 *0101, *0102, *0103 . . .
Symbol(s) HLA-DRB1 [ permanent dead link ]
Shared data
Locus chr.6 6p21.31

HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB1*01 gene products. It has been observed to be common among centenarians. [2] [3] [4]

Contents

Serology

DR1 serotype recognition of Some DRB1*01 allele-group gene products [5]
DRB1*DR1DR103Sample
allele%%%size (N)
*0101 97%6317
*0102 95%2035
*0103 56%12%1186
*0105 >50%2

The serology for the most common DR1 alleles is excellent. The serology for alleles *0104 , *0106 , *0109 , *0110 , *0112 , *0115 , and *0116 is unknown.

Disease associations

By serotype

DR1 is associated with seronegative [6] -rheumatoid arthritis, [7] [8] penicillamine-induced myasthenia, [9] and schizophrenia. [10] DR1 is increased in patients with systemic sclerosis and arthritis [11] and in ulcerative colitis with patients that have articular manifestations. [12]

By allele

DRB1*0101 is associated with rheumatoid arthritis, [13] in anti-Jk(a) mediated hemolytic transfusion reactions, [14] foliaceous pemphigus, [15] HTLV-1-associated myelopathy/tropical spastic paraparesis, and [16] lichen planus. [17] In lyme disease arthritis, *0101 appears to play a role in presentation of triggering microbial antigens. [18]

DRB1*0102 is associated with rheumatoid arthritis, [13] in anti-Jk(a) mediated hemolytic transfusion reactions, [14] psoriasis vulgaris, [19] and recurrent respiratory papillomatosis [20]

DRB1*0103 is associated with colonic Crohn's disease [21] and ulcerative colitis. [22] [23]

By genotype

DRB1*0101/*0404 and *0101/*0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking. [24] these same genotypes are associated with rheumatoid vasculitis. [25]

ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR ab DR beta 1 SEI topdown.JPG
ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR αβ

By haplotype

DRB1*0102:DQB1*0501 is associated with psoriasis vulgaris [19] and tubulointerstitial nephritis & uveitis syndrome, [26] but is relatively protective against juvenile diabetes. [27]

DR1-DQ5 is associate with tubulointerstitial nephritis & uveitis syndrome. [26]

Diseases associated with HLA-DR and links to DR subpages(V - T)
ClassDiseaseAssociated DR234
alopecia areata DR5
anemia pernicious DR15
antiphospholipid syndrome, primary DR5 DR12
aneurysm coronary artery DR16
arteritis Takayasu's DR16
arthritis, rheumatoid juvenile DR4 DR5 DR14 DR15
pauciarticular, juv. DR8
Still's disease DR12
iritis w/juv. arthritis DR12
seropositive DR1 DR4 DR10
w/systemic sclerosis DR1
lyme disease induced DR4
tiopronin intolerance DR5 DR11 DR12
cardiomyopathy hypertrophic DR4 DR17
T. cruzi induced DR4 DR7 DR15
colitis Crohn's DR1
ulcerative DR1
diabetes juvenile (type 1) DR3 DR4 DR17 DR18
fatty liver (type 2) DR8
encephalomyelitis rabies vaccine-induced DR17
encephalopathy acute necrotizing DR52
epilepsy childhood DR5
infantile/spasm DR17
heart disease rheumatic DR16
hepatitis autoimmune DR2 DR4 DR17
primary biliary cirrhosis DR2 DR8
chronic type C DR11
lichen planus DR1 DR10
lupus,systemic DR3 DR4 DR52
hydralazine-induced DR4
with Sjögren syndrome DR15
lymphadenopathy generalized DR5
lymphoma, mycosis fungoides DR5
melioidosis DR16
myasthenia gravis DR3 DR6 DR13 DR14
penicillamine-induced DR1
myositis inflammatory inclusion body DR17 DR18 DR52
narcolepsy DR2 DR12
nephritis,tubulointerstitial DR1
nephropathy IgA-mediated DR4
polyglandular deficiency syndrome DR5
pemphigus foliaceous DR1
vulgaris DR4
psoriasis vulgaris DR1 DR7
papillomatosis,respiratory DR1
sarcoidosis non-chronic DR17 DR52
sclerosis,multiple DR2 DR15 DR53
"bout onset" multiple DR3
systemic DR4 DR11 DR16 DR52
vulval lichen DR12
schizophrenia DR1
susceptibility leprosy DR2
tuberculosis DR2
ragweed Ra6 allergy DR5
asthma, mite sensitive DR11
2ndary infection, AIDS DR3
aspergillosis DR15
Kaposi's sarcoma DR5
thyroid carcinomas DR8 DR11
ovarian/cervical cancer DR10 DR11 DR15
grape induced anaphylaxis DR11
Chlamydia pneumoniae DR52
thyroiditis Hashimoto's DR3 DR5
Graves' DR3 DR17 DR52
uveitis tubulointerstitial DR1
*references are provided on linked subpages

Rheumatoid arthritis

DR1 are associated with rheumatoid arthritis, and while not the strongest association with the highest risk for early onset arthritis is within the DR4-bearing Native American population. There frequency of DR4-DQ8 haplotypes reach extreme nodal levels. Arthritis has been identified in a pre-Columbian remains from Italy, the affected individual bearing the DRB1*0101 allele. [28] DRB1*0101 and most DR4 have in common a 'shared epitope'. [29] [30] In this hypothesis a common region of the beta chain, positions 67 to 74, are common and may be integral to presenting auto-immunological peptides.

Genetic linkage

DR1 Haplotypes
SerotypesDRADRB1
DR1*0101*0101
*0101*0102
*0101*0103
SerotypesDQA1DQB1DRB1
DR1-DQ5 (5.1, 1)*0101*0501*0101
*0101*0501*0102
*0101*0501*0103
SerotypesHLA-AHLA CHLA BDRB1
A3-Cw4-B35-DR1*0301*0401*3501*0101
A11-Cw4-B35-DR1*1101*0401*3501*0103
A33-Cw8-B14-DR1*3301*0802*1402*0102

HLA-DR1 is not genetically linked to DR51, DR52 or DR53, but is linked to HLA-DQ1 and DQ5 serotypes.

Related Research Articles

Human leukocyte antigen

The human leukocyte antigen (HLA) system or complex is a group of related proteins that are encoded by the major histocompatibility complex (MHC) gene complex in humans. These cell-surface proteins are responsible for the regulation of the immune system. The HLA gene complex resides on a 3 Mbp stretch within chromosome 6p21. HLA genes are highly polymorphic, which means that they have many different alleles, allowing them to fine-tune the adaptive immune system. The proteins encoded by certain genes are also known as antigens, as a result of their historic discovery as factors in organ transplants. Different classes have different functions:

HLA-DRB1

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. DRB1 encodes the most prevalent beta subunit of HLA-DR. DRB1 alleles, especially those encoding amino acid sequence changes at positions 11 and 13, are associated risk of rheumatoid arthritis.

HLA-DQ8

HLA-DQ8 (DQ8) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ8 is a split antigen of the DQ3 broad antigen. DQ8 is determined by the antibody recognition of β8 and this generally detects the gene product of DQB1*0302.

HLA-DQ2

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

HLA-DQ4

HLA-DQ4 (DQ4) is a serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β4 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ4 are encoded by the HLA-DQB1*04 allele group. This group currently contains 2 common alleles, DQB1*0401 and DQB1*0402. HLA-DQ4 and HLA-DQB1*04 are almost synonymous in meaning. DQ4 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ4.3 and DQ4.4, are also encoded by the DQA1*0303 and DQA1*0401 genes, respectively.

HLA-DQ6

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

HLA-DQ9

HLA-DQ9 (DQ9) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ9 is a split antigen of the DQ3 broad antigen. DQ9 is determined by the antibody recognition of β9 and this generally detects the gene product of DQB1*0303.

HLA-DQ1 Serotype that covers a broad range of HLA-DQ haplotypes.

HLA-DQ1 is a serotype that covers a broad range of HLA-DQ haplotypes. Historically it was identified as a DR-like alpha chain called DC1; later, it was among 3 types DQw1, DQw2 and DQw3. Of these three serotyping specificities only DQw1 recognized DQ alpha chain. The serotype is positive in individuals who bear the DQA1*01 alleles. The most frequently found within this group are: DQA1*0101, *0102, *0103, and *0104. In the illustration on the right, DQ1 serotyping antibodies recognizes the DQ α (magenta), where antibodies to DQA1* gene products bind variable regions close to the peptide binding pocket.

HLA-DR53

HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins.

HLA-DR16

HLA-DR16(DR16) is a HLA-DR serotype that recognizes the DRB1*1601, *1602 and *1604 gene products. DR16 is found in the Mediterranean at modest frequencies. DR16 is part of the older HLA-DR2 serotype group which also contains the similar HLA-DR15 antigens.

HLA-DR15

HLA-DR15 (DR15) is a HLA-DR serotype that recognizes the DRB1*1501 to *1505 and *1507 gene products. DR15 is found at high levels from Ireland to Central Asia. DR15 is part of the older HLA-DR2 serotype group which also contains the similar HLA-DR16 antigens.

HLA-DR14

HLA-DR14(DR14) is a HLA-DR serotype that recognizes the DRB1*1401 to *1408, *1410 to *1418, and other *14 gene products. DR14 serotype is a split antigen of the older HLA-DR6 serotype group which also contains the similar HLA-DR13 antigens.

HLA-DR11

HLA-DR11 (DR11) is a HLA-DR serotype that recognizes the DRB1*1101 to *1110. DR11 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR12 antigens.

HLA-DR12

HLA-DR12(DR12) is a HLA-DR serotype that recognizes the DRB1*1201 to *1203, *1206. DR12 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR11 antigens.

HLA-DR10

HLA-DR10 (DR10) is a HLA-DR serotype that recognizes the DRB1*1001 gene product.

HLA-DR5

HLA-DR5 (DR5) is a broad-antigen serotype that is further split into HLA-DR11 and HLA-DR12 antigen serotypes.

HLA-DR2

HLA-DR2 (DR2) of the HLA-DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group. This serotype primarily recognizes gene products of the HLA-DRB1*15 and HLA-DRB1*16 allele groups.

HLA-DR3

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is strongly associated with HLA-DR3 or HLA-DR4.

HLA-DR4

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

Anti-apolipoprotein antibodies

In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result AAHA are strongly implicated in autoimmune deep vein thrombosis.

References

  1. ↑ Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA (2006). "Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule". J. Biol. Chem. 281 (35): 25356–25364. doi:10.1074/jbc.M603969200. PMC   2730046 . PMID   16829512.
  2. ↑ "The genetics of exceptional human longevity".
  3. ↑ Willcox, B. J.; Willcox, D. C.; He, Q.; Curb, J. D.; Suzuki, M. (2006). "Siblings of Okinawan Centenarians Share Lifelong Mortality Advantages". The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 61 (4): 345–354. doi: 10.1093/gerona/61.4.345 . PMID   16611700.
  4. ↑ Garoyan, Georges (1990). Cent-quatorze ans de vie ou la longue histoire de Jeanne Calment, doyenné d'âge de France [One Hundred and Fourteen Years of Life or the Long History of Jeanne Calment, the Eldest of France]. Marseille: Université d'Aix-Marseille II. pp. 22–42.
  5. ↑ derived from IMGT/HLA
  6. ↑ Bardin T, Legrand L, Naveau B, Marcelli-Barge A, Debeyre N, Lathrop G, Poirier J, Schmid M, Ryckewaert A, Dryll A (1985). "HLA antigens and seronegative rheumatoid arthritis". Ann Rheum Dis. 44 (1): 50–53. doi:10.1136/ard.44.1.50. PMC   1001567 . PMID   3855618.
  7. ↑ Schiff B, Mizrachi Y, Orgad S, Yaron M, Gazit E (1982). "Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis". Ann Rheum Dis. 41 (4): 403–404. doi:10.1136/ard.41.4.403. PMC   1000958 . PMID   6981387.
  8. ↑ "HLA-DR antigens in rheumatoid arthritis. A Swiss collaborative study; final report. Swiss Federal Commission for the Rheumatic Diseases, Subcommission for Research". Rheumatol Int. 6 (2): 89–92. 1986. doi:10.1007/bf00541511. PMID   3489975. S2CID   189901283.
  9. ↑ Delamere J, Jobson S, Mackintosh L, Wells L, Walton K (1983). "Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features". Ann Rheum Dis. 42 (5): 500–504. doi:10.1136/ard.42.5.500. PMC   1001283 . PMID   6605118.
  10. ↑ Narita K, Sasaki T, Akaho R, Okazaki Y, Kusumi I, Kato T, Hashimoto O, Fukuda R, Koyama T, Matsuo K, Okabe Y, Nanko S, Hohjoh H, Tokunaga K (2000). "Human leukocyte antigen and season of birth in Japanese patients with schizophrenia". Am J Psychiatry. 157 (7): 1173–1175. doi:10.1176/appi.ajp.157.7.1173. PMID   10873932.
  11. ↑ Szücs G, Szekanecz Z, Zilahi E, et al. (2007). "Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity". Rheumatology (Oxford, England). 46 (6): 989–993. doi: 10.1093/rheumatology/kem021 . PMID   17384178.
  12. ↑ Núñez C, Alecsandru DM, Mendoza JL, et al. (2006). "Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients". Hum. Immunol. 67 (4–5): 324–330. doi:10.1016/j.humimm.2006.02.035. PMID   16720213.
  13. 1 2 Kapitány A, Zilahi E, Szántó S, et al. (2005). "Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary". Ann. N. Y. Acad. Sci. 1051 (1): 263–270. Bibcode:2005NYASA1051..263K. doi:10.1196/annals.1361.067. PMID   16126967. S2CID   6515443.
  14. 1 2 Reviron D, Dettori I, Ferrera V, et al. (2005). "HLA-DRB1 alleles and Jk(a) immunization". Transfusion. 45 (6): 956–959. doi:10.1111/j.1537-2995.2005.04366.x. PMID   15934994. S2CID   20473677.
  15. ↑ del Mar Sáez-de-Ocariz M, Vega-Memije M, Zúñiga J, Salgado N, Ruíz J, Balbuena A, Domínguez-Soto L, Granados J (2005). "HLA-DRB1*0101 is associated with foliaceous pemphigus in Mexicans". Int J Dermatol. 44 (4): 350. doi:10.1111/j.1365-4632.2005.02038.x. PMID   15811100. S2CID   21880556.
  16. ↑ Sabouri A, Saito M, Usuku K, Bajestan S, Mahmoudi M, Forughipour M, Sabouri Z, Abbaspour Z, Goharjoo M, Khayami E, Hasani A, Izumo S, Arimura K, Farid R, Osame M (2005). "Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals". J Gen Virol. 86 (Pt 3): 773–781. doi: 10.1099/vir.0.80509-0 . PMID   15722539.
  17. ↑ Luis-Montoya P, Yamamoto-Furusho JK, Vega-Memije E, et al. (2007). "HLA-DRB1*0101 is associated with the genetic susceptibility to develop lichen planus in the Mexican Mestizo population". Archives of Dermatological Research. 299 (8): 405–407. doi:10.1007/s00403-007-0769-2. PMID   17665209. S2CID   5986703.
  18. ↑ Steere AC, Klitz W, Drouin EE, et al. (2006). "Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide". J. Exp. Med. 203 (4): 961–971. doi:10.1084/jem.20052471. PMC   3212725 . PMID   16585267.
  19. 1 2 Cardoso C, Uthida-Tanaka A, Magalhães R, Magna L, Kraemer M (2005). "Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis". Eur J Dermatol. 15 (3): 159–63. PMID   15908298.
  20. ↑ Bonagura V, Vambutas A, DeVoti J, Rosenthal D, Steinberg B, Abramson A, Shikowitz M, Gjertson D, Reed E (2004). "HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis". Hum Immunol. 65 (8): 773–782. doi:10.1016/j.humimm.2004.05.014. PMID   15336778.
  21. ↑ Fernandez L, Mendoza J, Martinez A, Urcelay E, Fernandez-Arquero M, Garcia-Paredes J, Peña A, Diaz-Rubio M, de la Concha E (2004). "IBD1 and IBD3 determine location of Crohn's disease in the Spanish population". Inflamm Bowel Dis. 10 (6): 715–722. doi:10.1097/00054725-200411000-00004. PMID   15626888. S2CID   23790673.
  22. ↑ Puzanowska B, Prokopowicz D, Ziarko S, Radziwon P, Lapinski T (2003). "The incidence of HLA DRB1*0103 in ulcerative colitis patients in north-eastern Poland". Hepatogastroenterology. 50 (53): 1436–8. PMID   14571756.
  23. ↑ Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell D (1997). "Genetic markers may predict disease behavior in patients with ulcerative colitis". Gastroenterology. 112 (6): 1845–1853. doi:10.1053/gast.1997.v112.pm9178675. PMID   9178675.
  24. ↑ Mattey DL, Thomson W, Ollier WE, et al. (2007). "Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study". Arthritis Rheum. 56 (5): 1408–1416. doi:10.1002/art.22527. PMID   17469097.
  25. ↑ Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA (2004). "Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis". Arthritis Rheum. 50 (11): 3476–3484. doi:10.1002/art.20588. PMID   15529352.
  26. 1 2 Levinson R, Park M, Rikkers S, Reed E, Smith J, Martin T, Rosenbaum J, Foster C, Sherman M, Holland G (2003). "Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome". Invest Ophthalmol Vis Sci. 44 (2): 653–657. doi: 10.1167/iovs.02-0376 . PMID   12556395.
  27. ↑ Thomson G, Valdes AM, Noble JA, et al. (2007). "Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis". Tissue Antigens. 70 (2): 110–127. doi:10.1111/j.1399-0039.2007.00867.x. PMID   17610416.
  28. ↑ Fontecchio G, Fioroni MA, Azzarone R, et al. (2007). "Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain". International Journal of Immunopathology and Pharmacology. 20 (1): 103–9. doi:10.1177/039463200702000112. PMID   17346433. S2CID   2067413.
  29. ↑ Gregersen PK, Silver J, Winchester RJ (1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis Rheum. 30 (11): 1205–1213. doi: 10.1002/art.1780301102 . PMID   2446635.
  30. ↑ Morel PA, Erlich HA, Fathman CG (1988). "A new look at the shared epitope hypothesis". Am. J. Med. 85 (6A): 20–22. doi:10.1016/0002-9343(88)90375-0. PMID   2462347.
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