^

Health

A
A
A

Immunologic methods of diagnostics of hereditary diseases

 
, medical expert
Last reviewed: 06.07.2025
 
Fact-checked
х

All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.

We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.

If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.

Recently, the main histocompatibility complex - HLA (Human Leukocyte Antigens) has come to be considered as an important immunological marker of population genetics. The antigens of this system are determined immunologically in blood leukocytes. The HLA gene complex is compactly located on the short arm of chromosome 6 (6p21.3). The localization of this system and the extent of its loci on the chromosome allowed us to calculate that the complex constitutes approximately 1/1000 of the gene pool of the organism. Histocompatibility antigens participate in the regulation of the immune response of the organism, in maintaining immune homeostasis. Due to their polymorphism and compact localization of HLA antigens, they have acquired great importance as a genetic marker.

Currently, more than 200 alleles of this system have been discovered; it is the most polymorphic and biologically significant of the human body's genetic systems. Disorders of various functions of the major histocompatibility complex contribute to the development of a number of diseases, primarily autoimmune, oncological, and infectious.

According to the location of the HLA complex on chromosome 6, the following loci are distinguished: D/DR, B, C, A. New loci G, E, H, F have been discovered relatively recently; their biological role is currently being actively studied. Three classes of antigens are distinguished in the major histocompatibility complex. Class I antigens are encoded by loci A, B, C. New loci also belong to this class. Class II antigens are encoded by loci DR, DP, DQ, DN, DO. Genes of classes I and II encode transplantation antigens. Genes of class III encode complement components (C2, C4a, C4b, Bf), as well as the synthesis of isoforms of a number of enzymes (phosphoglucomutase, glycoxylase, pepsinogen-5, 21-hydroxylase).

The presence of Ag associated with a certain disease in a person allows us to assume an increased predisposition to this pathology, and in some correlations, on the contrary, resistance to it.

Determination of HLA system antigens is carried out on lymphocytes isolated from peripheral blood using histotyping sera in a microlymphocytotoxic reaction or molecular genetic methods.

Establishing associative links between diseases and the antigen of the major histocompatibility complex allows:

  • identify groups at increased risk of developing the disease;
  • determine its polymorphism, that is, identify groups of patients with features of the course or pathogenesis of the disease; in this regard, an analysis of the syntropy of diseases can be carried out, identifying the genetic prerequisites for the combination of various forms of pathology; association with antigens that determine resistance to diseases allows identifying individuals with a reduced risk of developing this pathology;
  • conduct differential diagnostics of diseases;
  • determine the prognosis;
  • develop optimal treatment tactics.

Since most diseases do not have a direct connection with the antigens of the major histocompatibility complex, the "two-gene" theory was proposed to explain the association between diseases and HLA antigens. According to this theory, there is an immune response gene (genes) (Ir gene) that is closely associated with HLA antigens and genes that regulate the immune response. Protector genes determine resistance to diseases, and provocative genes determine sensitivity to certain diseases.

The relative risk of the disease for individuals with the corresponding genotype is calculated using the formula: x = [h p × (1 - h c )] / [h c × (1 - h p )], where h p is the frequency of the trait in patients, and h c is the frequency in individuals in the control group.

Relative risk shows the magnitude of the association of the disease with a certain Ag/Ag of the HLA system (gives an idea of how many times higher the risk of developing the disease is in the presence of Ag compared to its absence). The higher this indicator in a patient, the higher the associative connection with the disease.

Association of human diseases with HLA-Ag (gene frequency,%)

Diseases

HLA

Control group,%

Sick,%

Relative risk

Rheumatology

Ankylosing spondylitis

B27

5-7

90-93

90-150

Reiter's syndrome

B27

6-9

69-76

32-49.6

Arthritis caused by infections:

- Yersinia

B27

58-76

17.59

- Salmonella

B27

60-69

17.57

Psoriatic arthritis

B13

9-37

4.79

Rheumatoid arthritis

Dw4

12-19

48-72

3.9-12.0

DR4

20-32

70

4.9-9.33

Behcet's syndrome

B5

13

48-86

7.4-16.4

SKV

B5

11-34

1.83

B8

19-48

2.11

Bw15

6-10

21-40

5.1

DR2

26.4

57.1

3.80

DR3

22.2

46.4

2.90

Gougerot-Sjogren syndrome

B8

38-58

3.15

Dw3

26

69-87

19.0

Cardiology

IHD

B7

27.8

45.8

2.19

B14

7.5

14.8

2.14

B15

11.1

20.4

2.05

Cw4

18.7

32.8

2.12

Hypertension

B18

10.4

22.6

2.52

Aw19

12.6

28.3

2.74

Endocrinology

Type 1 diabetes

B8

32

52-55

2.1-2.5

B18

5-59

1.65

B15

12

18-36

1.89-3.9

Dw3

26

48-50

2.9-3.8

Dw4

19

42-49

3.5-3.9

DR3 DR3/DR4

20

60

6.10 33

Hyperthyroidism

B8

21

35-49

2.34-3.5

D3

26

61

4.4

DR3

20

51

4.16

Subacute thyroiditis (de Quervain's)

Bw35

13

63-73

16.81

Dw1

33

2.1

Addison's disease

B8

20-80

3.88-6.4

Dw3

26

70-76

8.8-10.5

Itsenko-Cushing syndrome

A1

49

2.45

Gastroenterology

Pernicious anemia

B7

19

26-52

1.7-3.1

DR5

6

25

5.20

Atrophic gastritis

B7

37

2.55

Peptic ulcer of the duodenum

A2

48.1

61.3

1.7

A10

20.6

63.3

6.65

B14

4.0

10.3

2.76

B15

6.6

24.4

4.56

B40

9.72

23.3

2.82

Autoimmune hepatitis

B8

16

37-68

2.8-4.1

DR4

24

71

7.75

HBsAg carriers

Bw41

12

11.16

B15

10-19

0.29

Diseases

HLA

Control group,%

Sick,%

Relative risk

Dermatology

Psoriasis

Bw17

6-8

22-36

3.8-6.4

B13

3-5

15-27

4.2-5.3

Bw16

5

15

2.9

Dermatitis herpetiformis

B8

27-29

62-63

4.00-4.6

DR3

19

80

16.60

Scleroderma

B7

24

35

1.7

Pemphigus

A10

3.1

Atopic dermatitis

B13

6.86

21.28

3.67

B27

9.94

25.53

3.11

A10/B13

0.88

8.51

10.48

Eczema

A10

19.64

36.67

2.37

B27

9.94

26.67

3.29

Urticaria and Quincke's edema

B13

6.86

21,21

3.65

B5.8

1.42

12,12

9.57

B5.35

0.71

6.06

9.02

Neurology

Multiple sclerosis

A3

25

36-37

2.7-2.8

B7

25-33

36-42

1.4-2.0

Dw2

16-26

60-70

4.3-12.2

DR2

35

51.2

1.95

DR3

20

32.5

1.93

Myasthenia

B8

21-24

52-57

3.4-5.0

A1

20-25

23-56

3.8

DR3

26

50

2.5

Pulmonology

Bronchial asthma (in patients aged 19-30 years)

B21

4.62

12.5

2.95

B22

9.94

19.64

2.22

B27

12.31

37.5

4.27

B35

0.11

5.36

51.4

B27/35

0.47

7.14

16.2

Other diseases

Vasomotor rhinitis

A3

26.98

52.38

2.98

B17

7.57

28.57

4.88

A3/10

2.72

23.83

11.18

B7/17

0.47

9.52

22.28

The data presented in the table show that the strongest associative links are found for diseases with a polygenic or multifactorial type of inheritance.

Thus, the determination of antigens of the major histocompatibility complex on blood cells (leukocytes) allows us to identify the degree of individual predisposition of a person to a certain disease, and in some cases use the research results for differential diagnostics, prognosis assessment and selection of treatment tactics. For example, the detection of HLA-B27 antigens is used in the differential diagnostics of autoimmune diseases. It is detected in 90-93% of patients of the Caucasian race with ankylosing spondylitis and Reiter's syndrome. In healthy representatives of this race, HLA-B27 antigens are detected in only 5-7% of cases. HLA-B27 antigens are often detected in psoriatic arthritis, chronic inflammatory bowel diseases occurring with sacroiliitis and spondylitis, uveitis and reactive arthritis.

trusted-source[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ]

You are reporting a typo in the following text:
Simply click the "Send typo report" button to complete the report. You can also include a comment.