Biology:HLA-DR3

From HandWiki
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[yes|permanent dead link|dead link}}]
EBI-HLA DRA*01:01
Identifiers
beta 1 *03:01 *03:01 *03:02 *03:03 *03:04
Symbol(s) HLA-DRB1[yes|permanent dead link|dead link}}]
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
Shared data
Locus chr.6 6p21.31

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).

References

  1. ↑ derived from IMGT/HLA
  2. ↑ Wiencke K; Karlsen TH; Boberg KM; Thorsby, E.; Schrumpf, E.; Lie, B. A.; Spurkland, A. (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. ↑ "HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections". Hum. Immunol. 11 (2): 99–103. 1984. doi:10.1016/0198-8859(84)90048-X. PMID 6333416. 
  4. ↑ "HLA antigen frequencies in HIV-1-related Kaposi's sarcoma". J. Acquir. Immune Defic. Syndr. 3 (Suppl 1): S51–5. 1990. PMID 2395088. 
  5. ↑ Weil, Leonora (2014). Quick Reference Guide to Medicine and Surgery. Edinburgh: Mosby: Elsevier. pp. 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. 
  7. ↑ "HLA and Mooren's ulceration". Br J Ophthalmol 84 (1): 72–5. 2000. doi:10.1136/bjo.84.1.72. PMID 10611103. 
  8. ↑ "Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study". Neurology 51 (3): 742–7. 1998. doi:10.1212/wnl.51.3.742. PMID 9748020. 
  9. ↑ "MHC-extended haplotypes in families of patients with Graves' disease". Hum Immunol 36 (2): 99–111. 1993. doi:10.1016/0198-8859(93)90112-E. PMID 8096501. 
  10. ↑ "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. doi:10.1191/096120399678847560. PMID 10192503. 
  11. ↑ "Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT)". Tissue Antigens 55 (3): 275–9. March 2000. doi:10.1034/j.1399-0039.2000.550313.x. PMID 10777105. https://zenodo.org/record/1231460. 



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