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 associated with HLA-DR3 or HLA-DR4. Nearly half the US population has either DR3 or DR4 (only 1–3% have both), yet only a small percentage (about 0.5%) of these individuals will develop type 1 diabetes.

Illustration of an HLA-DR (Human MHC class II) antigen receptor with bound antigen
major histocompatibility complex, class II, DR3
Haplotypes groups DRA*01:DRB1*03:01 DRA*01:DRB1*03:02 DRA*01:DRB1*03:03 DRA*01:DRB1*03:04
Structure (See HLA-DR)
Identifiers
alpha *01:01
Symbol(s) HLA-DRA
EBI-HLA DRA*01:01
Identifiers
beta 1 *03:01 *03:01 *03:02 *03:03 *03:04
Symbol(s) HLA-DRB1
EBI-HLA DRB1*03:01
EBI-HLA DRB1*03:02
EBI-HLA DRB1*03:03
EBI-HLA DRB1*03:04
EBI-HLA DRB1*03:05 Archived 2007-09-26 at the Wayback Machine
Shared data
Locus chr.6 6p21.31

Serology
DR17 and DR3 recognition of some DRB1*03 alleles[1]
DRB1*DR3 DR17DR18Sample
allele % % %size (N)
03:01336409698
03:0224366317
03:0340605
03:0460205
03:07>501

Some DR3 also react with HLA-DR17 and/or HLA-DR18. The DRB1*03:04 primarily reacts with DR3. The serotypes of *03:05, *03:06, *03:08 to *03:31 are unknown.

Disease associations
Further information: HLA A1-B8-DR3-DQ2 § Importance to Medicine

By serotype

HLA-DR3 is associated with early-age onset myasthenia gravis, Hashimoto's thyroiditis (along with DR5), primary sclerosing cholangitis,[2] and opportunistic infections in AIDS,[3] but lowered risk for cancers.[4] It is also associated with membranous glomerulonephritis[5]

By allele

DRB1*03:01 (see HLA-DR17)

DRB1*03:02 (See HLA-DR18)

DRB1*03:04 is associated with Graves disease[6]

By haplotypes

DR3 and/or DQ2 is associated with Moreen's ulceration,[7] "bout onset" multiple sclerosis,[8] Graves' disease[9] and systemic lupus erythematosus[10]

DR3-DQ2 linkage is associated with coeliac disease, dermatitis herpetiformis, Diabetes mellitus type 1. DR3-DR2 is the serological marker for HLA-DQ2.5cis isoform. Although it cannot identify the alpha ".5" chain of HLA DQ, DQA1*05:01 gene is almost always found within the DR3-DQ2 haplotype Eurasia (however in older studies DQA1*05:05 is commonly confused with DQA1*05:01)
[11]

Genetic linkage

DR3 is genetically linked to HLA-DR52, DRB3*02:02 allele, and HLA-DQ2 (DQ2.5).

References
  1. derived from IMGT/HLA
  2. Wiencke K, Karlsen TH, Boberg KM, et al. (2007). "Primary sclerosing cholangitis is associated with extended HLA-DR3 and HLA-DR6 haplotypes". Tissue Antigens. 69 (2): 161–9. doi:10.1111/j.1399-0039.2006.00738.x. PMID 17257319.
  3. Pollack MS, Gold J, Metroka CE, Safai B, Dupont B (1984). "HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections". Hum. Immunol. 11 (2): 99–103. doi:10.1016/0198-8859(84)90048-X. PMID 6333416.
  4. Mann DL, Murray C, O'Donnell M, Blattner WA, Goedert JJ (1990). "HLA antigen frequencies in HIV-1-related Kaposi's sarcoma". J. Acquir. Immune Defic. Syndr. 3 Suppl 1: S51–5. PMID 2395088.
  5. Weil, Leonora (2014). Quick Reference Guide to Medicine and Surgery. Edinburgh: Mosby: Elsevier. p. 287. ISBN 978-0-7234-3553-2.
  6. Heward, Jm; Allahabadia, A; Sheppard, Mc; Barnett, Ah; Franklyn, Ja; Gough, Sc (Jul 1999). "Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501". Clinical Endocrinology. 51 (1): 115–8. doi:10.1046/j.1365-2265.1999.00755.x. ISSN 0300-0664. PMID 10468973. S2CID 6376169.
  7. Taylor C, Smith S, Morgan C, Stephenson S, Key T, Srinivasan M, Cunningham E, Watson P (2000). "HLA and Mooren's ulceration". Br J Ophthalmol. 84 (1): 72–5. doi:10.1136/bjo.84.1.72. PMC 1723219. PMID 10611103.
  8. Weinshenker B, Santrach P, Bissonet A, McDonnell S, Schaid D, Moore S, Rodriguez M (1998). "Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study". Neurology. 51 (3): 742–7. doi:10.1212/wnl.51.3.742. PMID 9748020. S2CID 11416838.
  9. Ratanachaiyavong S, Lloyd L, Darke C, McGregor A (1993). "MHC-extended haplotypes in families of patients with Graves' disease". Hum Immunol. 36 (2): 99–111. doi:10.1016/0198-8859(93)90112-E. PMID 8096501.
  10. Tjernström F, Hellmer G, Nived O, Truedsson L, Sturfelt G (1999). "Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus". Lupus. 8 (2): 103–8. doi:10.1191/096120399678847560. PMID 10192503. S2CID 26486050.
  11. Pera C, Delfino L, Longo A, Pistillo MP, Ferrara GB (March 2000). "Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT)". Tissue Antigens. 55 (3): 275–9. doi:10.1034/j.1399-0039.2000.550313.x. PMID 10777105.
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