Peculiarities of distribution of HLA class I antigens in patients with lihen planus

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Abstract


The article presents data on the distribution characteristics of the HLA class I system antigens in patients with lichen planus.

Aim. To study the patterns of distribution of HLA class I antigens in the general group. To establish the presence of an association of the disease with antigens of the HLA class I.

Material and methods. Laboratory analysis of the distribution of HLA class I antigens was carried out in 60 patients with various forms of lichen planus who consider themselves Russian on the basis of linguistic and ethnicity. The duration of the disease is 1–20 years.

Results. When analyzing the typing results in the general group of patients; a tendency to negative association of HLA-A11 and HLA-B7.

It was found that the frequency of haplotype combinations A1-B8; A2-B27; A2-B40; A3-B35 significantly exceeded that of healthy people. Analysis of the frequency of phenotypic combinations revealed a significant increase in A3-A19 and B12-B35.

Conclusion. Haplotype and phenotypic combinations of HLA A1-B8; A2-B27; A2-B40; A3-B35; A3-A19; B12-B35 are provoking factors in the development of various forms of the disease. The presence of these genetic traits in the individual increases the risk of developing lichen planus by 3–11 times. In turn; the HLA-A11 and B7 antigens play a protective role.


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Introduction Red lichen planus (LP) is an inflammatory disease that can affect the skin and mucous membranes, less commonly affecting nails and hair. In 1859, F. Gebra for the first time told and introduced red pointed lichen - lichen ruber acuminatus [1]. A dermatologist from England E. Wilson in 1869 was one of the first to give a clinically accurate description of this disease. With an emphasis on a feature consisting in flatter papular elements. The first report on KPL in Russian scientific literature was made by V.M. Bekhterev and A.G. Polotebnovym in 1881. In the entire system of morbidity, according to the profile of dermatology, CPL is 1.2% and is diagnosed up to 35% among cases with pathology of the oral mucosa, in children the disease is detected only in 1-10% of cases. In recent years, the volume of patients withLP has increased significantly; rare and difficult to diagnose forms have been reported. In patients with CPL of the oral mucosa, the disease proceeds with manifestations on the skin in 15% of all confirmed diagnoses. The genital area is affected in 25%. In 1–13%, an isolated defect in the nail plates is detected [2,3].
Today, the etiology and pathogenesis of LP remain insufficiently understood, and the treatment of dermatosis is to some extent not simple. After studying the latest data in publications of domestic and foreign authors, LP is considered a multifactorial disease, in the pathogenesis of which a variety of neuroendocrine, immune, intoxication and metabolic processes are involved. Despite the inconsistency of scientific articles, an increasing number of researchers believe that the main mechanism for the development of LP is the strengthening and acceleration of cellular and humoral immunity. [4, 5]. It has been established that the activation mechanism of immunocompetent cells in LP is the effect of viruses on the functioning of the immune system, leading to an increase in the activity of natural killer cells, a decrease in the synthesis and release of pro-inflammatory cytokines: IL-1, IL-15, TNFα and IFN-γ [6].
Without a doubt, it is known that immune disorders are controlled by genetic mechanisms, and immunogenetics today is an important and relevant field of immunology that carries out genetic regulation of the immune response. The main genetic structure responsible for this adjustment is the major histocompatibility complex, MHC (Major Complex histocompatibility). The first products of the genes of the main human histocompatibility complex were named HLA (human leukocyte antigens). [7.8].

The genes responsible for the severity of the immune response are associated with a major histocompatibility complex, while antigens can be used as genetic indicators of disease susceptibility. A reliable connection was established between the development of diseases, including those associated with infectious diseases and with antigens of the HLA complex. A large group of diseases has been identified that are more or less associated with certain HLA - antigens and haplotypes. Work on diabetes remains relevant; correlations between antigens of the main histocompatibility complex and activation of the protective mechanism of antitumor immunity have been established. Earlier, a work was published on the significance of histocompatibility antigens of HLA classes I and II in the formation of seroresistance after syphilis. In connection with modern natural imbalances and increased antigenic load on the body, not only functional, but also structural changes occur, therefore, the features of HLA antigens in patients with LP are of particular interest [9, 10].
According to the authors, in patients with common forms of CPL, HLA-A3, B5, B8, B35 antigens are more often determined, and with erosive-ulcerative and verrucous varieties, HLA-B8 and B5 are determined [11, 12, 13].
Objective: to study the characteristics of immunological reactivity and the distribution pattern of class I HLA antigens in patients with lichen planus, to establish their diagnostic and prognostic value. Compilation of prognostic criteria for patients in order to determine the likelihood of developing lichen planus.
Materials and methods. The clinical trial included 60 patients with lichen planus. The age spread at the time of the study ranged from 23 to 84 years. All patients consider themselves Russian on the basis of linguistic and ethnicity, the duration of the disease is 1-20 years. Class I HLA antigens were identified using a standard microlymphocytotoxicity test with a set of typing sera manufactured by Gisans CJSC (St. Petersburg). For the comparison group, a database of 795 healthy donors was used.
To establish the significance of differences in the nature of the distribution of antigens in the compared groups, we determined the agreement criterion (X2), adjusted for the continuity of Yeats variations. At zero frequencies and values ​​less than 5, in one of the fields of the table with four fields, the two-sided Fisher test was used, adjusted for the number of antigens. To determine the degree of association of lichen planus with immunogenetic parameters, a relative risk criterion (RR) was calculated. It was estimated that with an RR of 2.0 or more, there is a positive association of symptoms with the disease, i.e. there is a predisposition to the development of CPL. If the RR value is <1.0, the individual's resistance to this pathology is indicated. The etiological fraction (EF) characterizes the strength of the positive relationship and is calculated at RR> 2.0, i.e. indicates the amount of risk of developing the disease. The prophylactic (PF) fraction characterizes the strength of negative association and is calculated at RR <1.0.

Results and discussion. When analyzing the results of typing in the general group of patients, a negative associative relationship between HLA-A11 (х2 = 47.1; RR = 0.1) and HLA-B7 (х2 = 4.8; RR = 0.4) was revealed (Table. 1).
The frequency of haplotype combinations A1-B8 (15.0% versus 5.2%; х2 = 9.3; RR = 3.3), A2-B27 (6.6% versus 2.1%; х2 = 4) was determined , 8; RR = 3.1), A2-B40 (6.6% vs 2.2%; х2 = 4.3; RR = 3.1), A3-B35 (23.3% vs 5.5 %; х2 = 37.4; RR = 10.2) significantly exceeding that in healthy individuals (Table 2).
Analysis of the frequency of phenotypic combinations revealed a significant increase in A3-A19 (10.0% versus 1.6%; х2 = 17.9; RR = 11.0) and B12-B35 (8.3% versus 1.7%; х2 = 11.0; RR = 4.3) (Table 3).
Conclusions. The results suggest the presence of lichen planus with HLA complex antigens. The presence of HLA A1-B8, A2-B27, A2-B40, A3-B35, A3-A19, B12-B35 combinations in the antigen phenotype can be considered as genes that trigger a cascade of reactions leading to the acute clinical picture of CPL. The presence of the indicated genetic characters in the phenotype of an individual increases the risk of developing lichen planus by 3 to 11 times. And the presence of HLA A11 and B7 as antigens performing a protective function.
An important aspect in the study of tissue antigens is the determination of their importance in the development of a person's tendency to the emergence of a certain pathology. The upcoming work in this direction will contribute to the determination of the clinical polymorphism of lichen planus from the point of view of endogenous determinism and the establishment of genetic markers that serve as provoking agents for this disease.

About the authors

Irina I. Zakhur

Kirov State Medical Academy

Author for correspondence.
Email: bazhina.irisha@inbox.ru
ORCID iD: 0000-0002-1495-4038
SPIN-code: 2967-7211

Russian Federation, K. Marx str., 112, 610027, Kirov

post-graduate student

Sergei V. Koshkin

Kirov State Medical Academy

Email: koshkin_sergey@mail.ru
ORCID iD: 0000-0002-6220-8304
SPIN-code: 6321-0197

Russian Federation, K. Marx str., 112, 610027, Kirov

MD; Dr. Sci. (Med.); Professor

Galina A. Zaitseva

Kirov Research Institute of Hematology and Blood Transfusion FMBA

Email: bazhina.irisha@inbox.ru
SPIN-code: 9026-6571

Russian Federation, Krasnoarmeyskaya str., 72, 610027, Kirov

Dr. Sci. (Med.); Professor

Varvara A. Bobro

Kirov Regional Clinical Skin-Venereologic Dispensary

Email: bobro.va@inbox.ru
ORCID iD: 0000-0003-2306-1423

Russian Federation, Semashko str., 2a, 61030, Kirov

dermatovenerologist

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