Immunological methods

Recently, the main complex of histocompatibility - HLA( Human Leukocyte Antigens) began to be considered as an important immunological marker of population genetics. Ag of this system is determined immunologically in blood leukocytes. The complex of HLA genes is compactly located on the short arm of chromosome 6( 6p21.3).Localization of this system and the length of the location of its loci on the chromosome made it possible to calculate that the complex is about 1/1000 of the gene pool of the organism. Ag histocompatibility are involved in the regulation of the immune response of the body, in the maintenance of immune homeostasis. Due to their polymorphism and the compactness of the localization of Ar HLA have acquired great importance as a genetic marker.

Currently, more than 200 alleles of this system are found, it is the most polymorphic and biologically significant of the genetic systems of the human body. Violations of various functions of the main histocompatibility complex contribute to the development of a number of diseases, primarily autoimmune, oncological, and infectious.

According to the location of the HLA complex, the following loci are distinguished on chromosome 6: D / DR, B, C, A.More recently, new loci G, E, H, F have been discovered, their biological role is actively studied at the present time. In the main histocompatibility complex, three classes of Ar are distinguished. Class I Ag are encoded by loci A, B, C. The new loci also belong to this class. Class II arcs are encoded by the loci DR, DP, DQ, DN, DO.Genes I and II classes encode transplantation Ar. Class III genes code complement components( C2, C4a, C4b, Bf),

Fig. The arrangement of the locus of the main histocompatibility complex on the short arm of chromosome 6 of human

as well as the synthesis of isoforms of a number of enzymes( phosphoglucomutase, glycoxylase, pepsinogen-5, 21-hydroxylase).

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

The determination of the AG system of HLA is performed on lymphocytes isolated from peripheral blood, using histotyping sera in a micro-lymphocytotoxic reaction or by molecular genetic methods.

Fig. Arrangement of the locus of the main histocompatibility complex on the short arm of the human chromosome 6

Establishment of associative links between diseases and the main complex of histocompatibility complex allows:

to isolate groups at increased risk of developing the disease;

■ to determine its polymorphism, that is, to identify groups of patients with features of the course or pathogenesis of the disease;in the same plan, an analysis of the synthropy of diseases, the elucidation of the genetic preconditions for combining various forms of pathology;association with Ar, determining the resistance to diseases, allows to identify persons with a reduced risk of this pathology;

■ carry out differential diagnosis of diseases;

■ Determine the forecast;

■ Develop optimal treatment strategies.

Due to the fact that for most diseases there is no direct connection to the Arg of the main histocompatibility complex, a theory of "two genes" has been proposed to explain the association between diseases and Ag HLA, according to which the gene( genes) of the immune response( Ir gene), closely related to Ar HLA and the genes that regulate the immune response. Protective genes determine resistance to diseases, and genes-provocateurs - sensitivity to certain diseases.

In Table.data on the relationship between various diseases and the presence of Arg of the main histocompatibility complex are presented. The relative risk of the disease for persons with the corresponding genotype is calculated by the formula: x = [hp x( 1 - hc)] / [hc х( 1 - hp)], where hp is the frequency of the symptom in patients, and hc in the persons of the control group.

The relative risk shows the association value of the disease with a certain Ar / Arg of the HLA system( gives an idea of ​​how many times the risk of developing the disease is in the presence of Ar compared with its absence).The more this indicator in the patient, the higher the associative relationship with the disease.

Table The association of human diseases with HLA-Ar( gene frequency,%) [Yeager L., 1990;Frolkis AV, 1995;Petrova MA, 1997]

Table Association of Human Diseases with HLA-Ar( Gene Frequency,%) [Yeager L., 1990;Frolkis AV, 1995;Petrova MA, 1997]

Continuation of Table.

Continuation of Table.

End of Table.

End of Table.

Polynotic rhinosinusitis	A1	19.76	35.29	2.21
B8	14.91	32.35	2.73
B35	12.31	29.41	2.97
B8 / 35	1.53	8.82	6.22
A1 / B35	2.39	14.71	7.04

The data given in Table 10-2 shows that the strongest associative links are detected for diseases with a polygenic ormulti-factorial type of inheritance. Thus, the determination of Ar of the main histocompatibility complex on blood cells( leukocytes) allows to reveal the degree of individual predisposition of a person to a certain disease, and in some cases to use the results of studies for differential diagnostics, forecast estimation and choice of treatment tactics. For example, the detection of Ag HLA-B27 is used in the differential diagnosis of autoimmune diseases. It is found in 90-93% of patients of the Caucasoid race with ankylosing spondylitis and Reiter's syndrome. In healthy members of this race, the HLA-B27 Ag is detected in only 5-7% of cases. Ag HLA-B27 is often found in psoriatic arthritis, chronic inflammatory bowel diseases that occur with sacroiliac and spondylitis, uveitis and reactive arthritis.