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HLA-DR1

From Wikidoc - Reading time: 6 min
ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR αβ101
DR1 binding pocket with ligand PDB: 2G9H​ [1]
major histocompatibility complex, class II, DR1
Haplotypes groups DQA*01:DRB1*0101 DQA*01:DRB1*0102 DQA*01:DRB1*0103
Structure (See HLA-DR)
Identifiers
alpha *0101
Symbol(s) HLA-DRA
EBI-HLA DRA*0101
Identifiers
beta 1 *0101 *0102 *0103
Symbol(s) HLA-DRB1
EBI-HLA DRB1*0101
EBI-HLA DRB1*0102
EBI-HLA DRB1*0103
Shared data
Locus chr.6 6p21.31

HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB1*01 gene products.

Serology[edit | edit source]

DR01 serotype recognition of Some DRB1*01 allele-group gene products[2]
DRB1* DR1 DR103 Sample
allele % % % size (N)
0101 97% 6317
0102 95% 2035
0103 56% 12% 1186
0105 >50% 2

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

Disease Associations[edit | edit source]

By serotype[edit | edit source]

DR1 is associated seronegative[3]-rheumatoid arthritis[4][5], penicillamine-induced myasthenia[6], and schizophrenia[7]. DR1 is increased in patients with systemic schlerosis and arthritis[8] and in ulcerative colitis with patients that have articular manifestations.[9]

By allele[edit | edit source]

DRB1*0101 is associated with rheumatoid arthritis,[10] in anti-Jk(a) mediated hemolytic transfusion reactions,[11] foliaceous pemphigus,[12] HTLV-1-associated myelopathy/tropical spastic paraparesis, and [13] lichen planus[14]. In lyme disease arthritis, *0101 appears to play a role in presentation of triggering microbial antigens.[15]

DRB1*0102 is associated with rheumatoid arthritis,[10] in anti-Jk(a) mediated hemolytic transfusion reactions,[11] psoriasis vulgaris[16], and recurrent respiratory papillomatosis[17]

DRB1*0103 is associated with colonic Crohn's disease[18] and ulcerative colitis.[19][20]

By genotype[edit | edit source]

DRB1*0101/*0404 and *0101/*0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking.[21] these same genotypes are associated with rheumatoid vasculitis.[22]

By haplotype[edit | edit source]

DRB1*0102:DQB1*0501 is associated with psoriasis vulgaris[16] and tubulointerstitial nephritis & uveitis syndrome[23], but is relatively protective against juvenile diabetes.[24]

DR1-DQ5 is associate with tubulointerstitial nephritis & uveitis syndrome.[23]

Rheumatoid Arthritis[edit | edit source]

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 precolumbian remains from Italy, the affected individual bearing the DRB1*0101 allele[25]. DRB1*0101 and most DR4 have in common a 'shared epitope'.[26][27]. 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[edit | edit source]

DR1 Haplotypes
Serotypes DRA DRB1
DR1 *0101 *0101
*0101 *0102
*0101 *0103
Serotypes DQA1 DQB1 DRB1
DR1-DQ5 (5.1, 1) *0101 *0501 *0101
*0101 *0501 *0102
*0101 *0501 *0103
Serotypes HLA-A HLA C HLA B DRB1
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.

references[edit | edit source]

  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): 25356–64. doi:10.1074/jbc.M603969200. PMID 16829512.
  2. ↑ derived from IMGT/HLA
  3. ↑ 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): 50–3. PMID 3855618.
  4. ↑ 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): 403–4. PMID 6981387.
  5. ↑ "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. PMID 3489975.
  6. ↑ 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): 500–4. PMID 6605118.
  7. ↑ 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): 1173–5. PMID 10873932.
  8. ↑ 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): 989–93. doi:10.1093/rheumatology/kem021. PMID 17384178.
  9. ↑ 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): 324–30. doi:10.1016/j.humimm.2006.02.035. PMID 16720213.
  10. ↑ 10.0 10.1 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: 263–70. doi:10.1196/annals.1361.067. PMID 16126967.
  11. ↑ 11.0 11.1 Reviron D, Dettori I, Ferrera V; et al. (2005). "HLA-DRB1 alleles and Jk(a) immunization". Transfusion. 45 (6): 956–9. doi:10.1111/j.1537-2995.2005.04366.x. PMID 15934994.
  12. ↑ 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. PMID 15811100.
  13. ↑ 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): 773–81. PMID 15722539.
  14. ↑ 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". doi:10.1007/s00403-007-0769-2. PMID 17665209.
  15. ↑ 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): 961–71. doi:10.1084/jem.20052471. PMID 16585267.
  16. ↑ 16.0 16.1 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. PMID 15908298.
  17. ↑ 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): 773–82. PMID 15336778.
  18. ↑ 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): 715–22. PMID 15626888.
  19. ↑ 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. PMID 14571756.
  20. ↑ 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): 1845–53. PMID 9178675.
  21. ↑ 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): 1408–16. doi:10.1002/art.22527. PMID 17469097.
  22. ↑ 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): 3476–84. doi:10.1002/art.20588. PMID 15529352.
  23. ↑ 23.0 23.1 >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): 653–7. PMID 12556395.
  24. ↑ 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): 110–27. doi:10.1111/j.1399-0039.2007.00867.x. PMID 17610416.
  25. ↑ 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. PMID 17346433.
  26. ↑ 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): 1205–13. PMID 2446635.
  27. ↑ Morel PA, Erlich HA, Fathman CG (1988). "A new look at the shared epitope hypothesis". Am. J. Med. 85 (6A): 20–2. PMID 2462347.

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