HLA-DR1

DR1 binding pocket with ligand PDB: 2G9H​ [1]
major histocompatibility complex, class II, DR1
Haplotypes groups	DRA*01:DRB1*0101 DRA*01:DRB1*0102 DRA*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
Shared data
Locus	chr.6 6p21.31

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

Serology

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

By allele

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

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

By haplotype

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]

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's 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
	Grave's	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 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

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

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. 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): 50–53. doi:10.1136/ard.44.1.50. PMC 1001567. 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): 403–404. doi:10.1136/ard.41.4.403. PMC 1000958. 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. doi:10.1007/bf00541511. 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): 500–504. doi:10.1136/ard.42.5.500. PMC 1001283. 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): 1173–1175. doi:10.1176/appi.ajp.157.7.1173. 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): 989–993. 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): 324–330. doi:10.1016/j.humimm.2006.02.035. PMID 16720213.
10. 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: 263–270. doi:10.1196/annals.1361.067. PMID 16126967.
11. 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.
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): 350–350. doi:10.1111/j.1365-4632.2005.02038.x. 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): 773–781. doi:10.1099/vir.0.80509-0. 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". Archives of Dermatological Research. 299 (8): 405–407. 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): 961–971. doi:10.1084/jem.20052471. PMC 3212725. PMID 16585267.
16. 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.
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): 773–782. doi:10.1016/j.humimm.2004.05.014. 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): 715–722. doi:10.1097/00054725-200411000-00004. PMID 15626888.
19. 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.
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): 1845–1853. doi:10.1053/gast.1997.v112.pm9178675. 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): 1408–1416. 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): 3476–3484. doi:10.1002/art.20588. PMID 15529352.
23. 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.
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): 110–127. 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): 1205–1213. doi:10.1002/art.1780301102. PMID 2446635.
27. 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.