HLA-DR3 explained
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.
Serology
DR17 and DR3 recognition of some DRB1*03 alleles[1] | DRB1* | DR3 | DR17 | DR18 | Sample |
| allele | % | % | % | size (N) |
| 03:01 | 33 | 64 | 0 | 9698 |
| 03:02 | 24 | 3 | 66 | 317 |
| 03:03 | 40 | | 60 | 5 |
| 03:04 | 60 | 20 | | 5 |
| 03:07 | >50 | | | 1 |
|
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
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).
Notes and References
- http://www.ebi.ac.uk/imgt/hla/allele.html derived from IMGT/HLA
- Wiencke K . Primary sclerosing cholangitis is associated with extended HLA-DR3 and HLA-DR6 haplotypes . Tissue Antigens . 69 . 2 . 161–9 . 2007 . 17257319 . 10.1111/j.1399-0039.2006.00738.x . Karlsen TH . Boberg KM . Thorsby . E. . Schrumpf . E. . Lie . B. A. . Spurkland . A..
- Pollack MS, Gold J, Metroka CE, Safai B, Dupont B . HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections . Hum. Immunol. . 11 . 2 . 99–103 . 1984 . 6333416 . 10.1016/0198-8859(84)90048-X .
- Mann DL, Murray C, O'Donnell M, Blattner WA, Goedert JJ . HLA antigen frequencies in HIV-1-related Kaposi's sarcoma . J. Acquir. Immune Defic. Syndr. . 3 . S51–5 . 1990 . Suppl 1 . 2395088 .
- Book: Weil, Leonora. Quick Reference Guide to Medicine and Surgery. Mosby: Elsevier. 2014. 978-0-7234-3553-2. Edinburgh. 287.
- 10468973 . Jul 1999 . Heward, Jm . Allahabadia, A . Sheppard, Mc . Barnett, Ah . Franklyn, Ja . Gough, Sc . 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 . 51 . 1 . 115–8 . 0300-0664 . Clinical Endocrinology . 10.1046/j.1365-2265.1999.00755.x. 6376169 .
- Taylor C, Smith S, Morgan C, Stephenson S, Key T, Srinivasan M, Cunningham E, Watson P . HLA and Mooren's ulceration . Br J Ophthalmol . 84 . 1 . 72–5 . 2000 . 10611103 . 10.1136/bjo.84.1.72 . 1723219.
- Weinshenker B, Santrach P, Bissonet A, McDonnell S, Schaid D, Moore S, Rodriguez M . Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study . Neurology . 51 . 3 . 742–7 . 1998 . 9748020 . 10.1212/wnl.51.3.742. 11416838 .
- Ratanachaiyavong S, Lloyd L, Darke C, McGregor A . MHC-extended haplotypes in families of patients with Graves' disease . Hum Immunol . 36 . 2 . 99–111 . 1993 . 8096501 . 10.1016/0198-8859(93)90112-E.
- Tjernström F, Hellmer G, Nived O, Truedsson L, Sturfelt G . 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 . 1999 . 10192503 . 10.1191/096120399678847560. 26486050 .
- Pera C, Delfino L, Longo A, Pistillo MP, Ferrara GB . Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT) . Tissue Antigens . 55 . 3 . 275–9 . March 2000 . 10777105 . 10.1034/j.1399-0039.2000.550313.x .
