HLA-DR1 explained

DR1 binding pocket with ligand [1]

major histocompatibility complex, class II, DR1

Haplotypes groupsDRA*01:DRB1*01:01 DRA*01:DRB1*01:02 DRA*01:DRB1*01:03
Structure (See HLA-DR)
Identifiers

alpha *01:01

Symbol(s)HLA-DRA
EBI-HLADRA
  • 01:01
Identifiers

beta 1 *01:01, *01:02, *01:03 . . .

Symbol(s)HLA-DRB1
Shared data
Locuschr.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]

Serology

DR1 serotype recognition of Some DRB1*01 allele-group gene products[5]
DRB1* DR1DR103 Sample
allele % % % size (N)
97% 6317
95% 2035
56% 12% 1186
>50% 2

The serology for the most common DR1 alleles is excellent. The serology for alleles,,,,,, and 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*01:01 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, *01:01 appears to play a role inpresentation of triggering microbial antigens.[18]

DRB1*01:02 is associated with rheumatoid arthritis,[13] in anti-Jk(a) mediated hemolytic transfusion reactions,[14] psoriasis vulgaris,[19] and recurrent respiratory papillomatosis[20]

DRB1*01:03 is associated with colonic Crohn's disease[21] and ulcerative colitis.[22] [23]

By genotype

DRB1*01:01/*0404 and *01:01/*0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking.[24] these same genotypes are associated with rheumatoid vasculitis.[25]

By haplotype

DRB1*01:02:DQB1*05:01 is associated with psoriasis vulgaris[19] and tubulointerstitial nephritis & uveitis syndrome,[26] but is relatively protective against juvenile diabetes.[27]

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

Rheumatoid arthritis

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*01:01 allele.[28] DRB1*01:01 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

SerotypesDRA DRB1
DR1
  • 01:01
  • 01:01
  • 01:01
  • 01:02
  • 01:01
  • 01:03
SerotypesDQA1 DQB1 DRB1
DR1-DQ5 (5.1, 1)
  • 01:01
  • 05:01
  • 01:01
  • 01:01
  • 05:01
  • 01:02
  • 01:01
  • 05:01
  • 01:03
SerotypesHLA-A HLA C HLA B DRB1
A3-Cw4-B35-DR1
  • 03:01
  • 04:01
  • 35:01
  • 01:01
A11-Cw4-B35-DR1
  • 11:01
  • 04:01
  • 35:01
  • 01:03
A33-Cw8-B14-DR1
  • 33:01
  • 08:02
  • 14:02
  • 01:02

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

Notes and References

  1. Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA . 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 . 2006 . 16829512 . 10.1074/jbc.M603969200 . 2730046. free .
  2. Web site: The genetics of exceptional human longevity.
  3. Siblings of Okinawan Centenarians Share Lifelong Mortality Advantages. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 61. 4. 345–354. 10.1093/gerona/61.4.345. 16611700. 2006. Willcox. B. J.. Willcox. D. C.. He. Q.. Curb. J. D.. Suzuki. M.. free.
  4. Book: 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. 22–42.
  5. http://www.ebi.ac.uk/imgt/hla/allele.html 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 . HLA antigens and seronegative rheumatoid arthritis . Ann Rheum Dis . 44 . 1 . 50–53 . 1985 . 3855618 . 10.1136/ard.44.1.50 . 1001567.
  7. Schiff B, Mizrachi Y, Orgad S, Yaron M, Gazit E . Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis . Ann Rheum Dis . 41 . 4 . 403–404 . 1982 . 6981387 . 10.1136/ard.41.4.403 . 1000958.
  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 . 3489975 . 10.1007/bf00541511. 189901283 .
  9. Delamere J, Jobson S, Mackintosh L, Wells L, Walton K . Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features . Ann Rheum Dis . 42 . 5 . 500–504 . 1983 . 6605118 . 10.1136/ard.42.5.500 . 1001283.
  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 . Human leukocyte antigen and season of birth in Japanese patients with schizophrenia . Am J Psychiatry . 157 . 7 . 1173–1175 . 2000 . 10873932 . 10.1176/appi.ajp.157.7.1173.
  11. Szücs G . Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity . Rheumatology . 46 . 6 . 989–993 . 2007 . 17384178 . 10.1093/rheumatology/kem021 . vanc. Szekanecz Z . Zilahi E . 3 . Kapitany . A. . Barath . S. . Szamosi . S. . Vegvari . A. . Szabo . Z. . Szanto . S.. free .
  12. Núñez C . Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients . Hum. Immunol. . 67 . 4–5 . 324–330 . 2006 . 16720213 . 10.1016/j.humimm.2006.02.035 . vanc. Alecsandru DM . Mendoza JL . 3 . Urcelay . E . Diazrubio . M . Delaconcha . E . Martinez . A.
  13. Kapitány A . Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary . Ann. N. Y. Acad. Sci. . 1051 . 1. 263–270 . 2005 . 16126967 . 10.1196/annals.1361.067 . vanc. Zilahi E . Szántó S . 3 . Szücs . Gabriella . Szabó . Zoltán . Végvári . Anikó . Rass . Péter . Sipka . Sándor . Szegedi . Gyula. 2005NYASA1051..263K . 6515443 .
  14. Reviron D . HLA-DRB1 alleles and Jk(a) immunization . Transfusion . 45 . 6 . 956–959 . 2005 . 15934994 . 10.1111/j.1537-2995.2005.04366.x . vanc. Dettori I . Ferrera V . 3 . Legrand . Dominique . Touinssi . Mhammed . Mercier . Pierre . De Micco . Philippe . Chiaroni . Jacques. 20473677 . free .
  15. del Mar Sáez-de-Ocariz M, Vega-Memije M, Zúñiga J, Salgado N, Ruíz J, Balbuena A, Domínguez-Soto L, Granados J . HLA-DRB1*0101 is associated with foliaceous pemphigus in Mexicans . Int J Dermatol . 44 . 4 . 350 . 2005 . 15811100 . 10.1111/j.1365-4632.2005.02038.x. 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 . 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 . 2005 . 15722539 . 10.1099/vir.0.80509-0. free .
  17. Luis-Montoya P . 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. 2007 . 17665209 . 10.1007/s00403-007-0769-2 . vanc. Yamamoto-Furusho JK . Vega-Memije E . 3 . Rodríguez-Carreón . A. . Ruiz-Morales . J. A. . Vargas-Alarcón . G. . Domínguez-Soto . L. . Granados . J.. 5986703 .
  18. Steere AC . Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide . J. Exp. Med. . 203 . 4 . 961–971 . 2006 . 16585267 . 10.1084/jem.20052471 . vanc. Klitz W . Drouin EE . 3 . Falk . BA . Kwok . WW . Nepom . GT . Baxter-Lowe . LA . 3212725.
  19. Cardoso C, Uthida-Tanaka A, Magalhães R, Magna L, Kraemer M . Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis . Eur J Dermatol . 15 . 3 . 159–63 . 2005. 15908298.
  20. Bonagura V, Vambutas A, DeVoti J, Rosenthal D, Steinberg B, Abramson A, Shikowitz M, Gjertson D, Reed E . HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis . Hum Immunol . 65 . 8 . 773–782 . 2004 . 15336778 . 10.1016/j.humimm.2004.05.014.
  21. Fernandez L, Mendoza J, Martinez A, Urcelay E, Fernandez-Arquero M, Garcia-Paredes J, Peña A, Diaz-Rubio M, de la Concha E . IBD1 and IBD3 determine location of Crohn's disease in the Spanish population . Inflamm Bowel Dis . 10 . 6 . 715–722 . 2004 . 15626888 . 10.1097/00054725-200411000-00004. 23790673 . free .
  22. Puzanowska B, Prokopowicz D, Ziarko S, Radziwon P, Lapinski T . The incidence of HLA DRB1*0103 in ulcerative colitis patients in north-eastern Poland . Hepatogastroenterology . 50 . 53 . 1436–8 . 2003. 14571756.
  23. Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell D . Genetic markers may predict disease behavior in patients with ulcerative colitis . Gastroenterology . 112 . 6 . 1845–1853 . 1997 . 9178675 . 10.1053/gast.1997.v112.pm9178675. free .
  24. Mattey DL . 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 . 2007 . 17469097 . 10.1002/art.22527 . vanc. Thomson W . Ollier WE . 3 . Batley . M. . Davies . P. G. . Gough . A. K. . Devlin . J. . Prouse . P. . James . D. W..
  25. Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA . Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis . Arthritis Rheum. . 50 . 11 . 3476–3484 . 2004 . 15529352 . 10.1002/art.20588.
  26. Levinson R, Park M, Rikkers S, Reed E, Smith J, Martin T, Rosenbaum J, Foster C, Sherman M, Holland G . 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 . 2003 . 12556395 . 10.1167/iovs.02-0376.
  27. Thomson G . 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 . 2007 . 17610416 . 10.1111/j.1399-0039.2007.00867.x . vanc. Valdes AM . Noble JA . 3 . Kockum . I. . Grote . M. N. . Najman . J. . Erlich . H. A. . Cucca . F. . Pugliese . A.. free .
  28. Fontecchio G . Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain . International Journal of Immunopathology and Pharmacology . 20 . 1 . 103–9 . 2007 . 17346433 . 10.1177/039463200702000112. vanc. Fioroni MA . Azzarone R . 3 . Battistoni . C . Cervelli . C . Ventura . L . Mercurio . C . Fornaciari . G . Papola . F. 2067413 . free .
  29. Gregersen PK, Silver J, Winchester RJ . The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis . Arthritis Rheum. . 30 . 11 . 1205–1213 . 1987 . 2446635 . 10.1002/art.1780301102. free .
  30. Morel PA, Erlich HA, Fathman CG . A new look at the shared epitope hypothesis . Am. J. Med. . 85 . 6A . 20–22 . 1988 . 2462347 . 10.1016/0002-9343(88)90375-0.

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