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HLA-DR1

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PDB rendering based on 1a6a.
DR1 binding pocket with ligand PDB: 2G9H​ [1]
major histocompatibility complex, class II, DR1
Haplotypes groups DRA*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[permanent dead link]
EBI-HLA DRA *01:01
Identifiers
beta 1 *01:01, *01:02, *01:03 . . .
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]

Serology

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DR1 serotype recognition of Some DRB1*01 allele-group gene products[5]
DRB1* DR1 DR103 Sample
allele % % % size (N)
*01:01 97% 6317
*01:02 95% 2035
*01:03 56% 12% 1186
*01:05 >50% 2

The serology for the most common DR1 alleles is excellent. The serology for alleles *01:04, *01:06, *01:09, *01:10, *0112, *0115, and *0116 is unknown.

Disease associations

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By serotype

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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

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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 in presentation 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

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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]

ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR αβ101
ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR αβ101

By haplotype

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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]


Diseases associated with HLA-DR and links to DR subpages(V - T)
Class Disease Associated DR 2 3 4
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

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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.[clarification needed] 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

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DR1 Haplotypes
Serotypes DRA DRB1
DR1 *01:01 *01:01
*01:01 *01:02
*01:01 *01:03
Serotypes DQA1 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
Serotypes HLA-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.

References

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  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. 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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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