IMMUNITY TRANSPLANT (Latin immunitas release, disposal of something; lat. to replace transplantare) — the condition of the raised immune responsiveness of an organism arising in response to tissue transfer or the body taken from other, genetically different individual. And. t. it is expressed to those stronger, than more genetic distinctions between the donor and the recipient. Y.t. develops at xenogenic — between individuals of different types and allogenic (hallo - or gomotransplantata) — between individuals of one look transplantations. Singenny, or isological, changes between genetically homogeneous individuals, enzygotic twins or animals of a purebred line as well as changes within one organism (autografts), are not followed by development And. t.
Most of researchers considers, as. t. serves as the main reason for death kseno-and allotransplants.
The earliest mentioning about And. t. as the reason of rejection of the replaced fabric belongs to Shen (G. Schone, 1912). A little later this point of view gained development in Fleischer's works (M. of S. Fleisher, 1918, 1922) and N. A. Sokolova (1923) which noted that hallo - and the heterografts of pieces of a kidney of Guinea pigs and closed glands of rabbits replaced to the recipient, previously immunizirovanny by the crushed fabric of the same body perished rather, than at transplantation to an intact animal.
I. N. Ishchenko (1935) and Item. The medical Avar (1944) the first paid attention to features of engraftment of transplants at repeated change to mice (a secondary transplant) and rabbits of rags of allogenic skin in comparison with primary transplant. The secondary transplant taken from the same donor perished rather in comparison with the piece of leather taken from other animal same look.
Features of death of a secondary transplant indicated that, as. t. has individual specificity. On a wedge, and experimental material it is found out that hypersensitivity to repeated changes arises not at once, and later about 1 — 2 weeks after transplantation and remains throughout the period from one month to several years. The sensitization develops first of all in regional to a transplant limf, nodes through which there is an outflow of a lymph from the replaced fabric; further other sites of an adenoid tissue of the owner join. It is not excluded that this process can be carried out also by lymphocytes of blood of the recipient by direct contact with alien cells at their passing through a transplant or regional limf. node.
There is an opinion, as. t. has no organ specificity and reaction is equally directed as against that fabric, edges changed, and against other tissues of the same donor.
And. t., however, not equally has the damaging effect on various fabrics. The facts received in clinic and in an experiment indicate that the allografted skin can undergo rejection while the replaced kidney taken from the same donor can remain in a viable state. There is a point of view that skin and a kidney have different sensitivity in relation to the factors defining death of allotransplant because of different degree of their vascularization. It is possible that vessels as a result of education in them the multiple thromboses leading to disturbance of blood supply of a transplant play an important role in reaction of a tissue incompatibility.
And. t. represents the general immunol. the reaction of an organism of the recipient directed against the replaced fabric. Saved up experimental and the wedge, data testify to that, as. t. develops generally as hypersensitivity of the slowed-down type: the organism of the recipient answers intradermal administration of extract from donor fabric in 2 — 3 days with local reaction in the form of infiltration by lymphocytes just as the person with tubercular hypersensitivity reacts to administration of tuberculine (see. Tuberkulinovaya allergy , Tuberculinodiagnosis ).
And. t. it is carried out as a result of cooperative interaction of system of immunocompetent cells of the recipient: macrophages, T - and B-lymphocytes. Main cellular component I. t. T-population, to be exact one of versions it — T-killers is. The immune response of lymphocytes sensibilized is shown by allogenic transplantation of the recipient at their addition to culture of cells of the donor on which they have the damaging effect (see. Immunocompetent cells ).
Lymphocytes of an immune organism gain the expressed ability to blast transformation (see. Blastotransformation of lymphocytes ) at addition of a mitogen — phytohemagglutinin (see. Lectins ) or donor cells (reaction of MLC — the mixed culture of lymphocytes). In the latter case in the presence of alien allogenic antigens the cultivated cells turn by division into young — blast elements and marked 3H thymidines are identified morphologically or on accumulation in the cells preparing for division. Donor cells process previously mitomitsiny or X-ray which kills them, but do not damage the antigens which are mitogens.
State And. t. it can be transferred by lymphocytes of a primed animal (adoptive immunity). At the same time animals from whom receive lymphocytes and the Crimea enter them, shall not have the expressed genetic distinctions.
Humoral factors of the recipient also take part in formation And. t. It is established that during reaction of a tissue incompatibility in blood the recipient has antibodies having cytotoxic effect on cells of the donor. Also adsorption of antibodies on a transplant during his death is shown. State And. t. it was passively postponed to the isolated allogenic cells of marrow and other fabrics by means of isoimmune antibodies, and also in special conditions at topical administration of the hyperimmune serum received as a result of repeated transplantation or artificial heteroimmunization when the antiserum capacity reaches rather high level. Most value of humoral factors of the recipient is shown at secondary changes. It is fixed that at allotransplantation of kidneys in the conditions of incompatibility on isoantigens of the AB0 system bystry rejection of a transplanted organ due to impact on it of alpha and beta and natural antibodies is observed. Acute rejection of allotransplants of kidneys is followed by falloff at patients in blood immunoglobulins (see) and complement (see). The life expectancies of the replaced fabric given about increase can serve as confirmation of told at hypo - both agammaglobulinemias at the person and conditions of the inborn or acquired deficit of factors of a complement at animals.
And. t., as well as others immunol, reactions, it can be weakened as a result of the radiation of an organism of the recipient, use of hormones of adrenocorticotropic action, antimetabolites (an imuran, Cyclophosphanum, a methotrexate) inhibiting various parties of exchange processes, introductions of alien cells in the period of embryonic development for the purpose of induction immunol, tolerances (see. unresponsiveness ), thymectomies, uses of anti-lymphocytic serum (ALS). In the latter case it is about a peculiar management of activity of the lymphoid device by means of the heteroimmune anti-lymphocytic serum received from large animals — horses, goats, donkeys, etc. ALS possesses a broad spectrum of activity on the recipient: reduces quantity of lymphocytes of T-population, reduces their ability to cooperative interactions, hypersensitivity of the slowed-down type, leads to reduction in blood of a complement (see. Anti-lymphocytic serum ).
There is no full clarity in a question of the mechanism of graft rejection yet. Data on a possibility of transfer deserve attention And. t. by means of the acellular dialyzed factor — «transfer factor» of not immune nature allocated from leukocytes and including polypeptide and polynucleotide chains, and also materials about features of behavior of an activated lymphocyte of in vitro in the presence of antigen. In the light of told it is possible to assume that rejection of genetically alien transplant is carried out thanks to infiltration of the replaced fabric by stimulated lymphocytes which in the presence of antigens of donor specificity will collapse, emitting biologically active agents (cellular mediators) having together with antibodies the damaging effect on a transplant.
Histocompatibility antigens (graft-specific antigens)
the Necessary condition of emergence at the recipient I. t. at allogenic changes hit in an organism of the recipient of alien antigenic substances of tissue of the donor — graft-specific antigens is. Graft-specific antigens represent the extensive group of substances capable to cause in the recipient a condition of a hyperreactivity to the replaced fabrics. They are localized both in cytoplasm, and in cellular membranes and are controlled by loci of histocompatability (see. Immunogenetics ). At mice is apprx. 15 loci of histocompatability. The greatest value has the locus of N-2 which is on the 17th chromosome and controlling synthesis more than 20 strong graft-specific antigens. Loci of N-1, N-Z, and also the locus linked to Y - hromoso - mine, have smaller value at allogenic transplantation, causing distinctions between the donor and the recipient on weak graft-specific antigens. Immunization of mice by cytoplasmatic fraction leads to reduction of life expectancy of gomotransplantirovanny skin twice.
Introduction of the fraction containing kernels to a lesser extent affects the term of life of skin allotransplants. The drugs prepared from cytoplasm of cells of mice had ability to exhaust specifically isoimmune antibodies of the hemagglutinating, hemolyzing and leykotsitotoksichesky character against antigens of a locus N-2. Noted feature of distribution of graft-specific antigens in a cell is characteristic not only of animals, it also takes place at the person. Graft-specific antigens are unstable. They lose the immunol, activity under the influence of periodate of sodium, phenol, urea, at pH lower than 5,0 and higher than 10,0, during the heating to t ° 50 °. Graft-specific antigens are steady against effect of DNA-ase and RNA elements, are not dialyzed, keep activity at lyophilizing (see). Attempts to biochemical characterize the fraction containing graft-specific antigens led to the conclusion that activity is to a great extent connected with a proteinaceous component.
R. A. Reisfeld and soavt. (1970) allocated from lymphocytes of the person water-soluble fraction by ultrasonic cell desintegration and centrifuging of cellular contents at 130 000 g with afterfiltration on G-200 sephadex, capable to inhibit e of serum isoimmune cytotoxically against antigens of leukocytes. The received fraction had the expressed specificity and exhausted antibodies only against those antigens which contained in leukocytes.
D. L. Mann and soavt. (1970) carried out biochemical, studying of properties of the water-soluble fractions received from the cellular membranes processed by papain, cultures of an adenoid tissue of the person and cells of a spleen of mice. The strong likeness of the fractions containing antigens of the person of the HLA system and antigens of a locus N-2 of mice was found. The received fractions had the same amino-acid structure and treated glycoproteins. As a result of studying of the water-soluble fraction received from cells of a spleen by processing by their papain and the subsequent their clarification, P. A. Peterson and soavt. (1974) came to conclusion that antigenic specificity is connected with two polypeptide chains, each of which is in a complex with beta2-microglobulin.
Despite efforts of many researchers, graft-specific antigens in a chemically pure look are not received yet.
Among a large number of antigens of erythrocytes at allogenic transplantations the antigens of the AB0 system defining have the greatest value blood groups (see).
By numerous works it is shown that transplantations of an allogenic kidney and other bodies shall be made surely taking into account a blood group from compatible donors since otherwise the transplanted organ perishes soon after operation. The point of view about an important role of antigens of the AB0 system in And. t. it will be coordinated with materials about the expressed sensitization of the recipient to group factors at allogenic changes. After allotransplantation by the burned patient of skin of donors with other blood group increase at recipients of a caption alpha and beta antibodies from cultivation of serum 1 is revealed: 64 to 1: 130 000. Reduction of life expectancy of transplants of the allogenic skin incompatible on a blood group at persons volunteers, previously sensibilized to group And - and to V-antigens is shown.
The important place in development And. t. occupy antigens of leukocytes. P. The medical Avar (1946) showed that introduction to a rabbit of leukocytes of the donor before allotransplantation (homotransplantation) is followed by immunization of an organism of the recipient with the subsequent bystry rejection of the replaced fabric. Similar results are received later in a wedge, conditions. Introduction to the recipient of the leukocytes allocated from blood of the donor before allotransplantation of skin was followed by acceleration of death of the replaced fabric. In experiments on induction immunol, the leukocytes entered in the embryonal period led tolerances on animals to strong engraftment of skin allotransplants. At the person antigens of leukocytes, in particular the HLA systems which is apprx. 80 (see first of all belong to graft-specific antigens. Blood groups, leukocytic groups ). Antigens of this system, in addition to leukocytes, are in all bodies and tissues of the person. PMCs equally matter at transplantation of kidneys, skin, heart and other bodies and fabrics. In the first decade after opening of subloci And yes In H LA antigens laid great hopes on them in overcoming a tissue incompatibility by selection to the recipient of the donor of a similar phenotype. Researchers believed that distinction on these antigens between the donor and the recipient is the main reason for development And. t. also represents the main obstacle in a way of use in clinic of allogenic transplants. Overseeing by destiny of transplants of kidneys and skin at unrelated persons when the donor and the recipient had the expressed distinctions on HLA antigens formed the basis for the similar conclusion.
However antigens of the AB0 system and HLA antigens do not define completely individual phenotypical antigenic distinctions causing development And. t. at allotransplantations. Came to this conclusion by results of transplantation among the persons which are in close relationship. A large number of possible HLA-fenoti-pov at persons in the mixed population induced researchers to limit a circle of observations by genetically related persons among which the donor and the recipient are a family (e.g., the brother and the sister). In the specified group of the person meet an identical HLA phenotype in 25% of cases, i.e. much more more often than in the usual mixed population of people.
At the allogenic skin transplantation executed on volunteers without use of immunodepressants (see. Immunodepressive substances ), transplants among relatives of an identical HLA phenotype, identical on both chromosomes controlling H LA antigens had the greatest life expectancy. Terms of life of transplants, according to Zh. Dosse et al. (1970, 1972), make 20 — 26 days. Smaller terms had the rags of skin replaced from the relatives who had only one general chromosome with the recipient i.e. identical on one haplotype. Duration of their life made 13 — 14 days. Similar results were received in 45 cases at transplantation of skin from children to fathers. To exclude influence of antigens of the AB0 system, researchers used skin transplants of donors of a blood group, identical or compatible to the recipient. At the specified combination the donor differed from the recipient on one HLA chromosome; on other HLA chromosome the donor and the recipient were identical. Terms of life of transplants made 13 — 16 days. Life expectancy of the rags of skin replaced from unrelated persons was even shorter and made 10 — 12 days. Similar results were received at transplantation of kidneys: from 44 transplants received from identical with the recipient on HLA antigens of donors in 2 years the replaced kidneys functioned at 23 recipients (52%), in 3 years — at 14 (31,8%), in 4 years — at 9 (20,4%).
Significantly life expectancy of transplanted organs in control group at transplantation of kidneys between the persons which do not have genetic proximity changed. More than by 3 times the specific weight of the transplants functioning at use of immunodepressants 2 years or a bigger time term was reduced. The saved-up materials on closely related changes at the person indicate that, in addition to the known systems of antigens of erythrocytes and leukocytes, also other insufficiently studied antigenic factors which are also causing development matter And. t. at allotransplantation of bodies and fabrics.
At mice some antigens of a tissue incompatibility were established only by means of MLC. Serol, reactions were unsuitable for identification of these genetic factors. The available literature indicates existence of similar antigens at the person. Two groups of genetically related persons were studied. The first included enzygotic twins at whom all genetic systems matched. In these conditions as Bach showed (F. N of Bach) and soavt. (1970), the stimulation of lymphocytes estimated by quantity absorbed by the sharing cells of thymidine was not observed, marked radioactive hyzone. Other group included 5 brothers and sisters of one parents with the identity established serol, method H LA antigens of two couples. Studying of this group of people in a MLC response (MLC) showed essential distinctions. The expressed stimulation of lymphocytes at joint cultivation of cells of one couple from two inspected is noted. There are instructions on detection in rare instances during the carrying out family researches in MLC of increase in number of triggered cells caused by distinctions of HLA antigens on a sublocus of D.
The question of existence at the person of a locus of incompatibility, in addition to And, In, From the HLA system, does not raise doubts. The possibility of identification of this locus at the person with the help serol, reactions (limfotsitotoksichesky test) is essentially proved, but remains insufficiently fulfilled.
Selection of the donor in the light of told consists in the choice of the person having distinctions on the smallest number of antigens. The analysis of materials about phenotypical distinctions of individuals and value at allotransplantation led them to emergence of some other receptions. It is, in addition to MLC, about assessment of similarity of antigens of the donor and recipient on the basis of reaction of incompatibility at transplantation of pieces of skin of several donors to one previously sensibilized recipient (the third partner) with the help a transfer test — immunol, reactions of the lymphocytes of the recipient entered vnutrikozhno to the alleged donor and also serotypings. These receptions, except serotyping, did not receive use. Serotyping allows to define on what H LA antigens of subloci And, In, With the donor differs from the recipient, nevertheless serol, the method remains still insufficiently developed in the direction of identification of the graft-specific antigens relating to D and other subloci of the HLA system.
The destiny of the replaced fabric is defined not only antigenic distinction between a transplant and the owner, but also nek-ry other reasons, in particular the previous sensitization of the recipient as at transplantation in these conditions there is his accelerated rejection. In reaction of the sensibilized recipient to the replaced fabric humoral factors, and in particular anti-HLA - antibodies are of great importance.
Existence of HLA antibodies to HLA-An-tngenam before transplantation indicates the possible unsuccessful result of engraftment of a transplanted organ or fabric. The greatest value in formation of anti-HLA - antibodies before transplantation belongs, apparently, to the previous pregnancies; to a lesser extent hemotransfusions since at repeated hemotransfusions antibodies against antigens of the granulocytes which are available only in polymorphonuclear leukocytes and cells of marrow are formed can play a role.
Development transplantologies (see) in the future in many respects depends on further studying of antigenic structure of cells and tissues of the person and mechanisms of immune responses of a tissue incompatibility (see. Nesovmestimost immunological ). Knowledge of the endogenous inhibitors of immunity responsible to a great extent for maintenance immunol is represented especially important. homeostasis (see) an organism.
See also Organ and tissue transplantation .
From additional materials
Histocompatibility antigens — allogenic options of glycoproteins of cells, mainly their membranes, defining individual antigenic marking of cells of an organism.
At hit of histocompatibility antigens in genetically unrelated organism of the same biol, a look (by allotransplantation of fabrics and bodies, at hemotransfusion or its components, at pregnancy) there are various forms immunol, reactions of an organism — hypersensitivity of the slowed-down type (see. Allergy ), antibodies (see), unresponsiveness (see. unresponsiveness ). The most studied system of histocompatibility antigens at the person is HLA (Human Leucocyte Antigens) similar to system of N-2 antigens of mice. Most HLA are expressed in membranes of yadrosoderzhashchy cells — lymphocytes, polymorphonuclear leukocytes, the fixed cells of bodies and fabrics (see. Blood groups, leukocytic ). In a smaller measure they are expressed in thrombocytes, erythrocytes, and also in a blood plasma. Studying of histocompatibility antigens opens new opportunities for a systematics of diseases, their diagnosis and forecasting of a current.
Studying of histocompatibility antigens began in the late fifties 20 century when the French researcher Zh. Dosse (1958) revealed the first serum having ability to stick together leukocytes of 58% of almost healthy people. In 1980 for researches on immunology and genetics of histocompatibility antigens Zh. Dosse, J. Snell and Benaserraf (V. of Benacerraf) got the Nobel Prize.
HLA represent polyallelic system and are coded by five loci — A, B, C, D, DR, each of to-rykh combines the allelic genes holding symmetric position on a pair chromosome. It is known apprx. 100 HLA. According to the nomenclature of WHO of 1977 — 1980 during the writing of histocompatibility antigens after symbols of HLA through a hyphen give alphabetic reference of a locus and sequence number of allelic antigen. For designation of recently discovered antigens, presence to-rykh demands further confirmation, use an alphabetic symbol w (Workshop), to-ry have between designation of a locus and sequence number of allelic antigen. HLA of four loci (And, B, C, DR) designate SD (Serologically Determined — defined serological) as they are revealed serol, way, generally by means of isoimmune (alloimmune) serums in limfotsitotoksichesky test. Unlike them the locus of HLA-D received the designation LD (Lymphocyte Determined — - determined by lymphocytes) as antigens of this locus establish by means of the mixed culture based on short-term cultivation of lymphocytes of two genotypes.
The locus of HLA-A codes 20 allelic antigens. Less than 3% of antigens of a locus of H LA-A are unknown. This conclusion is based that the sum of gene frequencies of allelic antigens equal to unit is already close to this size. Three antigens — HLA-A9, HLA-A10, HLA-A19 — were complex. HLA-A9 includes two antigens — HLA-Aw23 and HLA-Aw24, HLA-A10 consists of two antigens — HLA-A25 and HLA-A26. H LA-Awl 9 include five antigens: HLA-A29, HLA-Aw30, HLA-Aw31, HLA-Aw32, HLA-Aw33.
The locus of HLA-B codes 42 allelic antigens. Discovery of new antigens in this locus happens preferential by division of one antigen into slightly new. HLA-B5 antigen includes HLA-Bw51 and HLA-Bw52, HLA-B12 antigen — HLA-Bw44 and HLA-Bw45, HLA-Bwl6 antigen — HLA-Bw38 and HLA-Bw39, HLA-Bw21 — HLA-Bw49 and HLA-Bw50 etc.
The locus of HLA-G is open relatively recently and remains insufficiently studied. It contains 8 allelic antigens: HLA-Cwl, HLA-Cw2, HLA-Cw3 etc.
The locus of HLA-D controls synthesis of 12 allelic antigens: HLA-Dwl, HLA-Dw2, HLA-Dw3 etc. Opening of HLA-D - antigens is connected using the MLC method (Mixed Lymphocyte Culture — the mixed culture of lymphocytes). Consider that antigens of this locus can Oyt are typed also serol, method.
A locus of HLA-DR otvetstven for formation of 10 allelic antigens: HLA-DRwl, HLA-DRw2, HLA-DRw3, HLA-D R w4, etc. The locus received the designation (DR-D related) because of the expressed similarity of antigens of this locus to HLA-O antigens. The yvorotok indicates ability of anti-HLA-D R-с it, in particular, to inhibit blast transformation of the mixed culture of lymphocytes. Feature of antigens of this locus is their expressed fabric specificity. Antigens of a locus HLA-DR find preferential in population of V-lymphocytes. Besides, they are found in monocytes, epithelial cells and spermatozoa.
Structurally the molecule HLA includes a heavy polypeptide chain with a molecular weight (weighing) 39 000 — 44 000 and the light chain presented P2-mikroglobulinom with a molecular weight of 12 000, to-rye are attached one to another by noncovalent bonds. Creation of HLA reminds a molecule of monomer of immunoglobulin of a class G. The tail of HLA polypeptides similar to a Fc-fragment of immunoglobulins is shipped in thickness of a lipidic cell membrane and is in strong connection with it. The ends of heavy and light polypeptide chains are outside turned, to-rye and cause specific reaction with anti-HLA-syvorotkami. On such type antigens of loci And, In, Page are constructed. Distinctiveness of antigens of a HLA-DR-locus is that they do not contain light chains — r2-mikroglo-bulina. The strong likeness in creation of HLA and immunoglobulins (existence at HLA of analogs of constant and variable parts and other features of a structure) is allowed to believe that HLA carry out similar with immunoglobulins (see) function. In this regard it is considered to be that histocompatibility antigens, having the receptor device, can take part in processes of cellular interactions at an immune response, formoobrazovatelny and differentsirovochny processes, perhaps, as mediators or humoral signals of activity of cells.
HLA are controlled by the genes located on the sixth couple of chromosomes — C6. Near a locus of HLA-B on its one side the gene of HLA-C and further a gene of H LA-A, on other side — a gene of a locus of HLA-O is located. Genes of loci will defend from each other at distance In and With, equal 0,2; With and And, equal 0,6; In and D, equal 0,7 santimorganid (a morganida — unit of relative distance between genes determined by the frequency of a crossing-over: 1 morganid corresponds to the frequency of a crossing-over in 1%). Near genes of HLA genes of recently discovered antigens of a blood plasma Rg, Ch representing allogenic options of a complement, immune response genes of 1 g, and also the pro-activator of a complement S2, SZ, S4 and a number of enzymes are located (an isoenzyme of erythrocytes fosfoglyukomu-Tazy — Z-PGMg, glyoxalases — GLO, a pepsinogen — PG5).
HLA antigens are of great importance at allogenic transplantations. Most accurately it is shown at closely related transplantations of kidneys at siblin-g (brothers or sisters of one parents). At renal transplantation from HLA identical brothers and sisters in 3 years of 91% of allotransplants of kidneys remained viable. Transplantation of kidneys among the same group of the brothers and sisters who do not have identical HLA showed what through the same span viable remained apprx. 40% of transplanted organs.
Obviously, the person in addition to HLA has also other systems of histocompatibility antigens, is chromosomal not linked to them. The main argument in favor of it is development of a secondary disease almost at 50% of patients at transplantation of the allogenic marrow received from donors of sibling with identical HLA antigens.
Extensive data confirm a certain communication of histocompatibility antigens with a number of diseases. There is a strong opinion that the expressed communication of histocompatibility antigens with diseases takes place at patients with changed immunol, the reactivity which is combined about a wedge, signs of damage of bones, mucous both choroids and growth of connecting fabric in places of defeat. The most significant connection of a disease is established with availability of HLA-B27 antigen. This antigen meets in population of healthy people frequency apprx. 6%. At the same time the frequency of antigen considerably increases at having Bekhterev's disease (see. Bekhtereva disease ). Men are ill preferential. Frequency of occurrence of HLA-B27 antigen at patients reaches 96%. Probability to ache with a chronic ankylosing spondylitis at the carrier of HLA-B27 antigen almost by 100 times big in comparison with the person which does not have this factor of histocompatability. At this disease there is a damage of small joints and the copular device of a rachis, and also lumbosacral joint. Diagnosis, osooyenno at early stages of a disease, is complicated. Therefore the research of patients on availability of HLA-B27 antigen is quite justified for specification of the diagnosis of this disease. Increase in frequency of availability of HLA-B27 antigen (to 76%) is noted also at a syndrome of Reuters (see. Reuters disease ), shown an acute inflammation of the forefront of a choroid of an eye (uveitis), the urinary channel (urethritis) and synovial membranes of joints (synovitis). To a lesser extent (to 35 — 30%) increase in frequency of occurrence of HLA-B27 antigen at juvenile (juvenile) arthritis is noted (see. Pseudorheumatism ), and also at the arthritis connected with psoriasis (see. Arthritises ), at patients multiple myeloma (see).
Correlation also between the frequency of occurrence of antigens of a locus of HLA-B, in particular HLA-B8, and autoimmune diseases is established. Diseases of closed glands concern to them, went. - kish. path, liver, nervous system, skin. Frequency of occurrence of HLA-B8 antigen averages at healthy faces 16%, at damage of adrenal glands — addisonovy disease (see) — reaches 80%, at a teenage (juvenile) diabetes mellitus — 30%, at herpetiform dermatitis (see) — 60%, at hron. forms hepatitis (see) — 40%, at hron, forms colitis (see) — 55%, at myasthenias (see) — 45%, at immunodeficiency (see. Immunological insufficiency ) — 50%. Increase of frequency of occurrence of this antigen is noted also at patients system lupus erythematosus (see) and at bronchial asthma at children (see. Bronchial asthma ). At patients with multiple sclerosis (see) increase in frequency of occurrence of the haplotype including HLA-A3 and HLA-B7 antigens is observed. NEA-B7-antigen has looking alike HLA-B8 antigen and quite often enters cross-reactions.
There is no accurate interpretation of distinctions in distribution of HLA antigens among healthy and sick yet. Polymorphism of HLA antigens, obviously, is result of the mutations in human genome fixed naturally as the useful sign facilitating immunol, recognition by the lymphoid device of the from the stranger and providing maintenance of a genetic homeostasis of an organism. The most reasonable the point of view about associations of histocompatibility antigens with general diseases on the basis of possible communication nek-ry of HLA antigens with an immune response gene of 1 g in view of their close arrangement on is represented one (Ss) to a chromosome (see also Immunohematology , Immunogenetics ).
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