HLA-DR4

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Illustration of an HLA-DR (Human MHC class II) antigen receptor with bound antigen
human major histocompatibility complex, class II, DR4
Haplotypes groups DRA*01:DRB1*0401 to DRA*01:DRB1*0413
Structure (See HLA-DR)
Identifiers
alpha *0101
Symbol(s) HLA-DRA
EBI-HLA DRA*0101
Identifiers
beta 1 *0401 to *0413
Symbol(s) HLA-DRB1
EBI-HLA DRB1*0401
EBI-HLA DRB1*0402
EBI-HLA DRB1*0403
EBI-HLA DRB1*0404
EBI-HLA DRB1*0405
EBI-HLA DRB1*0406
EBI-HLA DRB1*0407
EBI-HLA DRB1*0408
EBI-HLA DRB1*0409
EBI-HLA DRB1*0410
EBI-HLA DRB1*0411
EBI-HLA DRB1*0412
EBI-HLA DRB1*0413
Shared data
Locus chr.6 6p21.31

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

Serology

DR4 serological recognition of the gene products of some DRB1*04 alleles[1]
DRB1* DR4 Sample
allele  % size (N)
04:01 98 5118
04:02 92 1029
04:03 92 748
04:04 89 2164
04:05 91 505
04:06 89 83
04:07 86 846
04:08 86 258
04:09 95 13
04:10 84 29
04:11 93 76
04:12 >50 1
04:13 >30 3

The serological identification of DR4 is good. The serology of DRB1*04:17 to *04:60 is unknown.

Disease associations

By serotype

DR4 is associated with extraarticular[2]rheumatoid arthritis,[3] hydralazine-induced female systemic lupus erythematosus,[4] pemphigoid gestationis,[5] pemphigus foliaceus,[6] obstructive hypertrophic cardiomyopathy,[7] IgA nephropathy,[8] 'shared syndrome'-systemic sclerosis/rheumatoid arthritis[9] and polymyalgia rheumatica.[10]

By allele

DRB1*04 is associated with increased risk for alopecia areata.[11]

DRB1*04:01 is associated with multiple sclerosis,[12] rheumatoid arthritis,[13] type 1 diabetes,[14][15] lyme disease induced arthritis[16]

DRB1*04:02: drug-triggered[17]/idiopathic pemphigus vulgaris,[18][19] type 1 diabetes,[15] SLE associated anti-cardiolipin and anti-β2 glycoprotein I[20]

DRB1*04:03: polycystic ovary syndrome,[21] SLE associated anti-cardiolipin and anti-β2 glycoprotein I[22]

DRB1*04:04: anti-citrullinated fibrinogen[23] in rheumatoid arthritis,[13] autoimmune hepatitis[24]

DRB1*04:05: rheumatoid arthritis,[25] Autoimmune hepatitis,[26] type 1 diabetes[14][15]

DRB1*04:06: caspase-8 autoantibodies silicosis-systemic sclerosis (SSc)-systemic lupus erythematosus (SLE)[27]

DRB1*04:09: T. cruzi infection with cardiomyopathy[28]

By haplotype

DR4-DQ8 is a risk factor for papillary thyroid carcinoma,[29] juvenile diabetes, coeliac disease and rheumatoid arthritis.[30]

DRB1*04:DQA1*03:03-DQB1*04:01 haplotype: type III autoimmune polyglandular syndrome,[31] autoimmune hepatitis,[32] autoimmune pancreatitis[33]

DRB1*04:DQA1*03-DQB1*03:02 haplotype: Type 1 diabetes[34][35] with DRB1*04:01, *04:05, *04:02 increasing risk when DQ8 is present.[36]

By genotype

DRB1*01:01/*04:04 and *01:01/*04:01 increases risk of mortality in rheumatoid arthritis, with eschemic heart disease and smoking.[37] these same genotypes are associated with rheumatoid vasculitis.[38]

Genetic Linkage

DR4 Haplotypes
Serotypes DRA DRB1 DRB4
DR4-DR53 *0101 *0401 *0103
*0101 *0402 *01
*0101 *0403 *01
*0101 *0404 *01
*0101 *0405 *01
Serotypes DQA1 DQB1 DRB1
DR4-DQ7 (7.3, 3) *0303 *0301 *0401
DR4-DQ7 (8.1, 3) *0301 *0302 *0401
*0301 *0302 *0402
*0301 *0302 *0404
DR4-DQ4 (4.3) *0303 *0401 *0405
Serotypes HLA-A HLA-C HLA-B DRB1
A2-Cw10-B62(15)-DR4 *0201 *0304 *1501 *0401
A2-Cw10-B60(40)-DR4 *0201 *0304 *4001 *0402
A2-Cw5-B44(16)-DR4 *0201 *0501 *4402 *0401

References

  1. ↑ derived from IMGT/HLA
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  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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