HLA-DR53 explained

major histocompatibility complex, class II, DR53
Haplotypes	DRA*01:DRB4*0101 DRA*01:DRB4*0102 DRA*01:DRB4*0103 DRA*01:DRB4*0104
Structure (See HLA-DR)
Identifiers	alpha *0101
Symbol(s)	HLA-DRA
EBI-HLA	DRA*0101
Identifiers	beta 4 *0101 *0102 *0103 *0104
Symbol(s)	HLA-DRB4
EBI-HLA	DRB4*0101
EBI-HLA	DRB4*0102
EBI-HLA	DRB4*0103
EBI-HLA	DRB4*0104
Shared data
Locus	chr.6 6p21.31

HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins.

DRB3, DRB4, and DRB5 are minor DR beta encoding loci, they have been recognized as having distinct evolution.^[1] and the DRB4 locus presence is linked to HLA-DR7 seropositivity. The DRB4*locus was apparently duplicated from an ancestor of the DRB1-DRB4 common locus around 5 million years ago.^[2]

DRB4 locus is only apparent in a small subset of DQ haplotypes, and most individuals lack DRB4. In addition the level of normal expression is 8 fold lower than the DRB1 in cells which can express both.^[3] and lowered because of both transcriptional and post-transcriptional regulation.^[4]

Alleles

DR53 recognition of some DRB4* alleles^[5]

DRB4*	DR53	?	Sample
allele	%	%	size (N)
0101	95		38
0103	89		49

DR53 reactive alleles: DRB4*0101, *0103

Unknown reactivity: *0102, *0104 to *0107

Null alleles: *0101102N, *01030102N, *0201N, *0301N

Associated diseases

DRB4*01 is positively associated with Erythema multiforme,^[6] Crohn's disease,^[7] myasthenia gravis,^[8] rheumatoid arthritis^[9] Hashimoto's thyroiditis,^[10] vitiligo,^[11] primary biliary cirrhosis,^[12] clozapine-induced agranulocytosis,^[13] Vogt–Koyanagi–Harada disease,^[14]

HLA-DRB1 linkage

HLA-DR53 serotypes (HLA-DRB4) is linked to the following HLADR serotypes (HLA-DRB1) allele groups:

HLA-DR4 - DRB1*04

HLA-DR7 - DRB1*07

HLA-DR9 - DRB1*09

Notes and References

1. Gorski J, Rollini P, Mach B . Structural comparison of the genes of two HLA-DR supertypic groups: the loci encoding DRw52 and DRw53 are not truly allelic . Immunogenetics . 25 . 6 . 397–402 . 1987 . 3596674 . 10.1007/BF00396106. 25853147 .
2. Gyllensten U, Sundvall M, Ezcurra I, Erlich HA . Genetic diversity at class II DRB loci of the primate MHC . J. Immunol. . 146 . 12 . 4368–76 . 1991 . 10.4049/jimmunol.146.12.4368 . 2040804 . free .
3. Stunz LL, Karr RW, Anderson RA . HLA-DRB1 and -DRB4 genes are differentially regulated at the transcriptional level . J. Immunol. . 143 . 9 . 3081–6 . 1989 . 10.4049/jimmunol.143.9.3081 . 2809218 . free .
4. Leen MP, Gorski J . Differential expression of isomorphic HLA-DR beta genes is not a sole function of transcription . Hum. Immunol. . 50 . 2 . 111–20 . 1996 . 8891734 . 10.1016/0198-8859(96)00154-1.
5. http://www.ebi.ac.uk/imgt/hla/allele.html derived from IMGT/HLA
6. Lepage V, Douay C, Mallet C, etal . Erythema multiforme is associated to HLA-Aw33 and DRw53 . Tissue Antigens . 32 . 3 . 170–5 . 1988 . 3217933 . 10.1111/j.1399-0039.1988.tb01654.x.
7. Kobayashi K, Atoh M, Yagita A, etal . Crohn's disease in the Japanese is associated with the HLA-DRw53 . Exp. Clin. Immunogenet. . 7 . 2 . 101–8 . 1990 . 2322470 .
8. Morita K, Moriuchi J, Inoko H, Tsuji K, Arimori S . HLA class II antigens and DNA restriction fragment length polymorphism in myasthenia gravis in Japan . Ann. Neurol. . 29 . 2 . 168–74 . 1991 . 1672809 . 10.1002/ana.410290209. 45699820 .
9. Morling N, Andersen V, Fugger L, etal . Immunogenetics of rheumatoid arthritis and primary Sjögren's syndrome: DNA polymorphism of HLA class II genes . Dis. Markers . 9 . 5 . 289–96 . 1991 . 1686751 .
10. Terauchi M, Yanagawa T, Ishikawa N, Ito K, Fukazawa T, Maruyama H, Saruta T . Interactions of HLA-DRB4 and CTLA-4 genes influence thyroid function in Hashimoto's thyroiditis in Japanese population. . J Endocrinol Invest . 26 . 12 . 1208–12 . 2003 . 15055474 . 10.1007/bf03349159. 2344535 .
11. Zamani M, Spaepen M, Sghar S, Huang C, Westerhof W, Nieuweboer-Krobotova L, Cassiman J . Linkage and association of HLA class II genes with vitiligo in a Dutch population. . Br J Dermatol . 145 . 1 . 90–4 . 2001 . 11453913 . 10.1046/j.1365-2133.2001.04288.x. 25942367 .
12. Shimoda S, Nakamura M, Ishibashi H, Hayashida K, Niho Y . HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. . J Exp Med . 181 . 5 . 1835–45 . 1995 . 7536796 . 10.1084/jem.181.5.1835 . 2191998.
13. Corzo D, Yunis J, Salazar M, Lieberman J, Howard A, Awdeh Z, Alper C, Yunis E . The major histocompatibility complex region marked by HSP70-1 and HSP70-2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups. . Blood . 86 . 10 . 3835–40 . 1995 . 10.1182/blood.V86.10.3835.bloodjournal86103835 . 7579351. free .
14. Kobayashi H, Kokubo T, Takahashi M, Sato K, Miyokawa N, Kimura S, Kinouchi R, Katagiri M . Tyrosinase epitope recognized by an HLA-DR-restricted T-cell line from a Vogt-Koyanagi-Harada disease patient. . Immunogenetics . 47 . 5 . 398–403 . 1998 . 9510558 . 10.1007/s002510050375. 1592923 .