HLA-B27 by molecular genetic diagnosis

The main immunogenetic marker of a high predisposition to the development of ankylosing spondylitis (Bechterew's disease) and other related seronegative spondyloarthropathies.

The product of the HLA-B27 gene, the HLA-B27 antigen, belongs to the molecules of the main histocompatibility complex of the first class, MHC-I (MHC-major histocompatibility complex), which are involved in the presentation of peptide antigens for their recognition by T lymphocytes. This is important for the formation of an immune response to foreign antigens. The set of HLA antigens is unique for each person. MHC class I genes are located at three loci (A, B, and C) on the short arm of chromosome 6 and are characterized by a high degree of polymorphism. It has been established that genetic variations in the individual set of these antigens are associated with different susceptibility to various diseases.

There are 136 known allelic variants for the HLA-B gene. The frequency of occurrence of the allele 27 of locus B (HLA-B27) varies depending on the geographical region and ethnic group; subtypes of HLA-B27 are also distinguished. A positive result of typing HLA-B27 increases the risk of developing any disease from the group of spondyloarthritis by 20 times. Therefore, HLA-B27 typing can be used to assess the risk of developing spondyloarthritis.

In the differential diagnosis of joint syndrome, the presence of HLA-B27 is a characteristic feature of spondyloarthritis: this allele is present in 90-95% of patients with ankylosing spondyloarthritis, in 60-90% with reactive arthritis, in 50% with psoriatic arthropathy and 80-90% with juvenile ankylosing spondyloarthritis.

The presence of HLA-B27 in patients with other diseases with joint damage (gout, rheumatoid arthritis, septic arthritis) does not exceed 7-8%. Typing HLA-B27 is necessary in case of difficulties in making a diagnosis based on basic diagnostic criteria.

HLA-B27 is of the greatest importance in the diagnosis of early ankylosing spondylitis. In most cases, 5-10 years pass between the appearance of the first signs of the disease and the final diagnosis. This is because the main diagnostic criterion is the X-ray signs of sacroiliitis, which develops only after several years of inflammation in the sacroiliac joints. Patients with complaints of back pain without radiological signs of sacroiliitis do not come to the rheumatologist's field of view. The detection of HLA-B27 in such a situation may be sufficient grounds for referral to a specialist of a narrow profile. The test is indicated in the examination of patients with complaints of inflammatory pain in the back in the absence of radiological signs of sacroiliitis or in the examination of a patient with asymmetric oligoarthritis.

The presence of HLA-B27 is associated with an increased risk of extra-articular manifestations of ankylosing spondylitis. The associations of the HLA-B27 allele and acute anterior uveitis, aortic valve insufficiency, acute leukemia, IgA nephropathy, and psoriasis are of the greatest importance. HLA-B27-positive patients are more at risk of tuberculosis and malaria. On the other hand, the presence of HLA-B27 also plays a certain "protective" role: some viral infections (influenza, herpes virus infection type 2, infectious mononucleosis, hepatitis C, and HIV) occur in a milder form in carriers of HLA-B27.

It should be noted that there are other, both hereditary and acquired, risk factors for the development of spondyloarthritis. The absence of HLA-B27 does not contradict the diagnosis of Ankylosing spondylitis, in which case it is classified as HLA-B27-negative and develops at a later age than HLA-B27-positive spondylitis.

In addition, HLA-B27 typing is performed when predicting complications of rheumatoid arthritis. The presence of HLA-B27 is associated with a threefold increase in the risk of atlantoaxial subluxation.

Indications for the appointment:

• Differential diagnosis of early arthritis in children and adults,
• Diagnosis of ankylosing spondylitis, psoriatic arthritis, reactive arthritis,
• Reiter's syndrome,
• Arthritis in inflammatory bowel diseases,
• Recurrent uveitis,
• Juvenile rheumatoid and psoriatic arthritis,
• Ankylosing spondylitis.

Interpretation of the results:

Positively:

• Detection of HLA-B27 in the presence of clinical manifestations corresponding to this group of rheumatic diseases significantly increases the likelihood of diagnosis.
• Ankylosing spondylitis (90-95% of patients).
• In other seronegative arthropathies (including psoriatic) - 60-70%.

Negative:

• The absence of the HLA-B27 antigen significantly reduces the likelihood of a diagnosis of Seronegative Amyloarthopathy.