HLA-DR4 (DR4) is an HLA- DR

serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or Cell (biology), cells are classified together based on their shared reactivity ...

that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency

alleles An allele is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule. Alleles can differ at a single position through single nucleotide polymorphisms (SNP), but they can also have insertions and deletions ...

spread over large regions of the world.

Serology

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

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

, hydralazine-induced female

systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

, pemphigoid gestationis,

pemphigus foliaceus Pemphigus foliaceus is an autoimmune blistering disease of the skin. Pemphigus foliaceus causes a characteristic inflammatory attack at the subcorneal layer of epidermis, which results in skin lesions that are scaly or crusted erosions with an ...

, obstructive

hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ...

, IgA nephropathy, 'shared syndrome'-systemic sclerosis/rheumatoid arthritis and

polymyalgia rheumatica Polymyalgia rheumatica (PMR) is a systemic inflammatory disease characterized by pain or stiffness, usually in the neck, shoulders, upper arms, and hips, but which may occur all over the body. Almost all cases occur in people age 50 or older. ...

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By allele

DRB1*04 is associated with increased risk for

alopecia areata Alopecia areata (AA), also known as spot baldness, is a condition in which hair loss, hair is lost from some or all areas of the body. It often results in a few Baldness, bald spots on the scalp, each about the size of a coin. Psychological st ...

. DRB1*04:01 is associated with

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

, rheumatoid arthritis, type 1 diabetes, lyme disease induced arthritis. HLA-DRB1*04:01 gene variant is found three times more often in asymptomatic carriers of SARS-CoV-2 than in patients with symptoms of COVID-19. It is known that the prevalence of the HLA-DRB1*04:01 variant directly correlates with the latitude and longitude of the population. This variant of the gene is more common in northern and western Europe, which means that people of European descent are more likely to be asymptomatic carriers that can transmit the disease to more susceptible populations. DRB1*04:02: drug-triggered/idiopathic pemphigus vulgaris, type 1 diabetes, SLE associated anti-cardiolipin and anti-β₂ glycoprotein I. DRB1*04:03: polycystic ovary syndrome, SLE associated anti-cardiolipin and anti-β₂ glycoprotein I. DRB1*04:04: anti-citrullinated fibrinogen in rheumatoid arthritis, autoimmune hepatitis. DRB1*04:05: rheumatoid arthritis, Autoimmune hepatitis, type 1 diabetes. DRB1*04:06: caspase-8 autoantibodies silicosis-systemic sclerosis (SSc)-systemic lupus erythematosus (SLE). DRB1*04:09: ''T. cruzi'' infection with cardiomyopathy.

By haplotype

DR4- DQ8 is a risk factor for papillary thyroid carcinoma, juvenile diabetes,

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spelt ...

and

. DRB1*04:DQA1*03:03-DQB1*04:01 haplotype: type III autoimmune polyglandular syndrome, autoimmune hepatitis, autoimmune pancreatitis. DRB1*04:DQA1*03-DQB1*03:02 haplotype: Type 1 diabetes with DRB1*04:01, *04:05, *04:02 increasing risk when DQ8 is present.

By genotype

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

Genetic linkage

References

{{DEFAULTSORT:Hla-Dr4 4