[Behcet's disease and associations with HLA-B5 antigen (a review of literature and the authors' findings)].

AIM: To estimate the distribution of HLA Class I (A, B) antigens in patients with Behcet's disease (BD) and the association of HLA-B5 antigen with the clinical manifestations of the disease in different ethnic and population groups in relation to gender. SUBJECTS AND METHODS: The study covered 93 patients (68 males, 25 females) from the representatives of 24 ethnicities with the verified disease. HLA Class I antigens were typed by the microlymphocytotoxic technique, by applying an antileukocytic serum kit (GISANS, Saint Petersburg). RESULTS: In patients with BD, the prevalence of HLA-B5 antigen proved to be significantly higher than that in the controls (72.0 and 21%, respectively) and to be similar in patients of different ethnicities living in the Caucasus and Transcaucasus (80-83%) while the number of HLA-B5 antigen-positive patients with BD was thrice less in the Russian population than in other BD patients (p < 0.01). There was a significant correlation of HLA-B5 antigen with ocular lesion (retinal angiitis) predominantly in male patients with BD. CONCLUSION: The prevalence of HLA-B5 antigen was higher in patients with BD than in the population-based control. The diagnostic value of this antigen is not so great, for example, in the Russian population of patients with BD. The presence of HLA-B5 antigen in the phenotype of male patients with BD may be regarded as a prognostically poor marker of development of eye diseases.

[Allele polymorphism of alkaline phosphatase, acid soluble phosphatase, and vitamin D-binding protein genes in postmenopausal osteoporosis]. / Allel'nyi polimorfizm genov shchelochnoi fosfatazy, kisloi rastvorimoi fosfatazy i belka, sviazyvaiushchego vitamin D, pri postklimaktericheskom osteoporoze.

AIM: To study polymorphism of genes involved in mechanisms regulating metabolism of bone tissue: alkaline (ALPL) and acid (ACP1) phosphatases, vitamin D-binding protein (GC); to ascertain associations of their genotypes and alleles with osteoporosis (OP) and mineral density of spinal and femoral bone tissue (BTMD). MATERIAL AND METHODS: Relevant genetic examination was made in 70 females with OP diagnosed by the WHO criteria (1994) aged 60-79 years (mean age 71.0 +/- 6.2 years) and 51 OP-free females in the same age interval (mean age 69.0 +/- 5.6 years). Polymorphic sites of the genes were examined by polymerase chain reaction. Trinucleotide repeat, ARG105GLN polymorphism of restrictive fragment length (PRFL), [GC, TRH420LYS] PRFL were studied for ALPL gene, ACP1 gene and GC gene, respectively. RESULTS: Association was found between frequencies of genotypes SS, 2F and FS, F allele of GC gene with OP as well as between PRFL of the spine, femur and some GC genotypes in OP women. Genes ALPL and ACP1 were not associated with OP. CONCLUSION: It is suggested that genotypes SS, 2F and FS have marked functional differences in fixation and transport of vitamin D active metabolites involved in metabolism of bone tissue in OP.

[A search for genes of predisposition to rheumatoid arthritis]. / Poisk genov predraspolozhennosti k revmatoidnomu artritu.

Rheumatoid arthritis belongs to the group of autoimmune multifactor diseases with an essential involvement of genetic components in its genesis. The HLA DRB1* polymorphism was studied in 68 RA patients and in their 75 healthy relatives. 135 blood donors, who were tested at the Institute for Immunology of the Ministry of Health, Russian Federation, Moscow, were in the control group. The carrier-state of the HLA DRB1* 04 gene contributes to a higher probability of RA onset by 8.5 times, while the presence, in genotype, of genes HLADRB1* 02, 05, 06 reduces the risk of RA by 2.1, 2.3 and 7.2 times, respectively. Allele *0401 is encountered reliably more often in RA patients versus healthy controls. Within a sample of patients with familial RA, 43.9% turned out to be the carriers with various combinations of two alleles of genes coding the conservative amine acids of sequences QKRAA or QRRAA, which were named "shared epitope" (SE), versus 5.1% among the controls. The presence of homozygous "SE genotypes" among the RA patients contributed to a higher risk of morbidity by 5.8 times, while the carrier state of haplotypes with "duel SE positivity" enhanced the risk of morbidity by 17.8 times mainly due to the 01/0401 halotype. The RA linkage with two intragenic DNA markers, i.e. with the polymorphous micro-satellite replication of gene TCRA (CA)n and with the point-type changeability (localized in the coding area of the second variable region of V2 TCRD gene), was analyzed. The maximal possible value of the lod-point for (CA)n, i.e. replication of TCRA gene, was equal to +1.30 in males under the condition of zero recombination frequency, and to 16% of frequency recombination in females. The maximal possible value of the lod-point for the point-type changeability of gene TCRD was equal to +0.70 in males under the conditions of zero frequency recombination and to 40% of frequency recombination in females. The maximal lod-point value amounting to +1.20 in males and females in an identical frequency recombination of 5% was found on the basis of a three-point analysis of the linkage between RA and two intragenic markers from gene clusters coding the alpha- and beta-chains of T-cellular receptors. Therefore, our familial data are indicative of the opportunity of localizing the gene predisposed to RA is at a distance of 5 cM, in the direction of the telomere, from the locus of the examined (CA)n, i.e. replication of gene TCRA.

[The prevalence of rheumatoid arthritis and the rheumatoid factor in the native inhabitants of northeastern Siberia]. / Rasprostranennost' revmatoidnogo artrita i revmatoidnogo faktora u korennykh zhitelei Severo-Vostochnoi Sibiri.

AIM: The study of rheumatoid arthritis (RA) and rheumatoid factor (RF) prevalence among residents of eastern Chukotka--Eskimos and Chukchi. MATERIALS AND METHODS: Simultaneous total survey covered 974 of 1176(83.3%) residents of 4 villages in the eastern Chukotka. RESULTS: RA was diagnosed in 7(0.7%) examines. Clinical picture of the disease was characterized by for the most part symmetric affection of hand and feet joints, absence of systemic manifestations, favourable course and frequent absence of RF. RF positive titers (1:160 and higher) occurred in 23 of 804 examinees (2.9%), among Eskimos--6%. This was significantly higher than in Chukchi (2.0%) and in subjects of mixed nationality (1.3%). CONCLUSION: Prevalence and clinical picture of RA in residents of northeast Siberia were comparable with such observed in other epidemiological surveys in Russia and Alaska.

[An analysis of the linkage of hypertrophic cardiomyopathy and the delta locus of the T-cell receptor (TCRD) chain in the family of P]. / Analiz stsepleniia gipertroficheskoi kardiomiopatii i lokusa del'ta tsepi T-kletochnogo retseptora (TCRD) v sem'e P.

AIM: To estimate probability of location of the gene determining family hypertrophic cardiomyopathy (HCMP) in family P. on the 14th chromosome in segment 14q11 using parametric method "lod score". MATERIALS AND METHODS: The family of proband P. had multiple cases of HCMP. Dinucleotide GT repeat and NT 256 point variation located in the cluster of genes coding synthesis of TCRD (14q11 chromosome segment) were used as markers of HCMP gene (FHC-1 gene 14q1 chromosome segment). Allele polymorphism of the two markers was defined at polymerase chain reaction, restriction of the amplificate by restrictase BamHI (for NT 256 point variation) and vertical electrophoresis in polyacrylamide and agar gels. RESULTS: Basing on the distribution of the above markers in P. family, lod score estimates in all the standard values of recombination frequency were determined (0-0,45, step 0.05). The maximal estimate corresponded to zero recombination frequency and was equal to 1.17 (this was below the critical value 3). However, the obtained lod score value satisfied the chance ratio 15:1 in favor of the link presence. CONCLUSION: The data obtained evidence for the presence of the link of HCMP gene with marker locus TCRD which is nearby the identified locus of the disease (FHC-1-14q11.2 segment). This suggests that HCMP in family P may be due to mutant allele of the gene coding synthesis of beta-polypeptide chains of cardial myosin.

[Distribution of HLA class I antigen in Finno-Ugrian populations of Russia (Mordovians and Maris)]. / Raspredelenie HLA antigenov klassa I v finno-ugorskikh populiatsiiakh Rossii (mordva i mari)]

Distributions and gametic associations of HLA I antigens were studied in two Finno-Ugrian populations of Russia: Mordovians (300 subjects, including 148 Erzyas and 152 Mokshas) and Maris (137 subjects). Regarding the Mordovian population, Erzya and Moksh subpopulations significantly differed from each other only in the frequency of the A9 antigen. However, the Mari and Mordovian populations differed from each other considerably. Maris exhibited higher frequencies of antigens A9, B27, and B40 and lower frequencies of B5, B8, and B16 compared to Erzyas, as well as higher frequencies of A3, A28, B27, and B40 and lower frequencies of A10, B5, B8, B16, and B18 compared to Moksha. In addition, Erzyas, Mokshas, and Maris differed from one another in the gametic associations revealed. In general, our data indicated that the three populations, which display characteristic features of both Caucasoid and Mongoloid races, differ from one another with respect to the HLA genetic polymorphism. In all of the three populations, a positive association of the B27 antigen with spondylarthropathies (SAPs) was revealed. This confirms the hypothesis that B27 is involved in the pathogenesis of some rheumatoid diseases.

[Spondyloarthropathies and HLA-B27 subtypes in the populations of the Russian North]. / Spondiloartropatii i subtipy HLA-B27 v nekotorykh populiatsiiakh Severa Rossii.

The aim of the study was to investigate the role of HLA-B27 subtypes in development of ankylosing spondylitis and other seronegative spondylarthropathies. Using oligotyping techniques we studied native DNA of 219 HLA-B27 positive natives: 88 Chukotka residents and 131 Mordovians (Russian Ugro-Finnish population). Only subtypes HLA-B*2705 and B*2702 were revealed. A dominant subtype of HLA-B27 among the natives was HLA-B*2705: 99% among residents of Chukotka and 86% among Mordovians. It was established that among spondylarthropathic patients the frequency of B*2705 does not differ from its incidence in the studied populations. The data support the suggestion that several B27 subtypes and common genetic determinant of B27 gene may be involved in pathogenesis of spondylarthropathy.

[DNA typing of HLA class II genes among the aboriginal inhabitants of Chukotka]. / DNK tipirovanie HLA-genov II klassa sredi korennogo naseleniia Chukotki

Polymorphism of class II HLA genes was studied in native Chukotka inhabitants with the use of DNA oligotyping. The characteristics of the distribution of allelic variants of the loci HLA-DRB1, -DQA1, -DQB1, and -DPB1 were revealed; they were similar to those of other Subarctic Mongoloid populations and different from those for comparable populations of other climatic and geographic zones. Our data suggest that the specific features found for the distributions of some alleles of the loci examined are related to the geographic variation in the HLA gene system studied.

[DNA typing of allelic variants of HLA-B27: HLA-B*2705 is the predominant allele of the aboriginal population of the Chukot peninsula (Eskimos and Chukchi)]. / DNK-tipirovanie allel'nykh variantov HLA-B27: HLA-B*2705 iavliaetsia preobladaiushchim allelem sredi korennogo naseleniia chukotki (éskimosov i chukchei).

The purpose of the study was to estimate the relative frequency of the known HLA-B27 subtypes among HLA-B27 positive Chukot natives. Using oligotyping of the polymerase chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-27 positive individuals were success-fully typed. All had HLA-B*2705, including nine patients with ankylosing spondylitis and Reiter's syndrome, except for one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. Considering the HLA-B27 subtypes, the Chukot population groups are genetically more closely related to Caucasians than to Orientals.

[The epidemiology of spondyloarthropathies among the native inhabitants of Chukotka. 2. The prevalence of HLA-B27 in the population and among spondyloarthropathy patients]. / Epidemiologiia spondiloartropatii sredi korennykh zhitelei Chukotki. Soobshchenie 2. Raspredelenie HLA-B27 v populiatsii i sredi bol'nykh spondiloartropatiiami.

To establish the incidence of HLA-B27 among the indigenous population of Chukot Peninsula, a one-stage cross-sectional study was made of all the natives of the two settlements of eastern Chukot Peninsula (Sireniki and Novo-Chaplino). At the moment of examination altogether 640 natives lived in both settlements. Of these, 464 persons (72.5%) could be examined clinically; HLA typing could be performed in 439 persons (68.6%). Among the 439 natives examined, antigen B27 was identified in 141 cases (32.1%). Among Eskimos, the number of HLA-B27-positive individuals amounted to 39.7%, among Chukchi to 18.9% (p = 0.0005). Half-breeds occupied an intermediate position between the two groups. The frequency of NLA-B27-positive cases was 29.7% among them. 7 patients were diagnosed to have diseases belonging to the group of spondyloarthropathies. 2 persons presented with ankylosing spondyloarthritis, 2 with Reiter's syndrome, 2 with undifferentiated spondyloarthropathies and 1 with juvenile chronic arthritis. All the patients with ankylosing spondyloarthritis and Reiter's syndrome appeared HLA-B27-positive.

[Genetic determination of rheumatoid arthritis. Distribution of certain Mendelian markers in the light of correspondence of the disease heritability to the model of single autosomal two-allele locus with incomplete penetrance]. / Issledovanie geneticheskoi determinatsii revmatoidnogo artrita. Raspredelenie nekotopykh Mendelipuiushchikh markerov v srete sootvetstviia nasledovaniia zabolevaniia modeli odnogo autosomnogo dvukhallel'nogo lokusa s nepol'noi penetpantnost'iu.

The study on the nature of distribution of certain mendelian markers aimed at specifying their role in determination of rheumatoid arthritis disease was carried out, based on the material from the Family Data Bank of the Department of Epidemiology and Genetics of the rheumatic diseases in this institute comprising data on 200 families of patients with definite rheumatoid arthritis (RA). Antigens of HLA-system (the loci A, B, DR), ABO blood groups, Rh, MN and P, phenotypes of acid erythrocyte phosphatase and the types of haptoglobin were studied. Based on the data from this and the previous studies, it is established that the steadiest deviations of the RA patients groups from the general population concerned the frequency of HLA A11, B12, B27 and DR4, blood group P and phenotypes of the acid erythrocyte phosphatase. When using additional controls--a group of healthy mothers of women-probands from the families with the type of marriage "healthy x healthy", and analysing some pair combinations of the HLA system antigens, it was demonstrated that the most clearly their role in formation of the disease display the antigens DR4, and in their absence--DR3, and B12, whereas accumulation of A11 and B27 depended on the presence of other antigens of HLA loci--A and B. Taken together, these data may imply that genetic markers under study serve, when in certain combinations, as "modifiers" of the major gene, or, in a general case, of major genes of multifactorial disease affecting its appearance and clinical manifestations.

[Genetic variants of acid erythrocytic phosphatase as a risk factor of rheumatic fever]. / Geneticheskie varianty kisloi éritrotsitarnoi fosfatazy kak faktor riska revmatizma.

A study was made of the genetic variants (isoenzymes, phenotypes) of acid erythrocytic phosphatase (AcP) in 120 patients with rheumatic fever. There were 78 women and 42 men aged 16 to 57 years. The population data concerned with distribution of the AcP variants among the population of Moscow were used as control. As compared with control, the patients suffering from rheumatic fever demonstrated the accumulation of the rarely occurring variants of AcP (AC, BC and CC, in particular). A significant direct correlation was established between the activity of isoenzymes and relative risk of rheumatic fever incidence. The definite regularities in the distribution of AcP variants were found to depend on the disease clinical patterns (the articular syndrome, the times of the formation of heart diseases, the character of recurrent rheumocarditis). The data obtained can used for distinguishing the rheumatic fever risk groups and forecasting the rheumatic process (to a certain degree of probability).

[Participation of rat immunoglobulin light chains of the kappa and lambda type in formation of antibodies to the polysaccharide of group A streptococcus]. / Uchastie legkikh tsepei immunoglobulinov krysy kappa i lambda-tipa v obrazovanii antitel k polisakharidu streptokokka gruppa A.

The role of light kappa and lambda chains and also allelic variants of kappa chains of rat immunoglobins in the formation of antibodies to beta-N-acetyl-glucosamine polysaccharides of streptococcus group A of inbred rat strains MSU, WAG, August and hybrids of the first generation (MUS X WAG)F1 and (MSU X August)F1 was studied. From individual sera of immune rats fractions of specific antibodies to beta-N-acetyl-glucosamine were isolated. These antibodies differ in their affinity to antigenes. The retio of molecules with kappa and lambda light chain types was determined for the fraction of specific antibodies. The ratio of molecules kappa and lambda depends on the affinity of antibodies to beta-N-acetyl-glucosamine and on the genotype of the animals studied. Data obtained allow to conclude that differences in the functional activity of lambda chains between strains WAG and August, on one hand, and strain MSU, on the other, do exist. Functional differences releaved between these rat strains were confirmed by analyzing corresponding antibody fractions to beta-N-acetylglucosamine in F1 hybrids. Differences between allelic variants of kappa chains in the formation of antibodies to beta-N-acetylglucosamine of polysaccharides were not found.

[Immune response of rats of inbred strains to the polysaccharide of group A streptococci]. / Immunnyi otvet krys inbrednykh linii na polisakharid streptokokka gruppy A

Immune response to polysaccharide of group A streptococcus was studied in rats of inbred strains MCY, VAG and August. Pure antibodies to beta-N-acetylglucosamine were isolated; their chromatography (by affinity) was conducted, and the content of the molecules of the IgG and IgM classes was established in each antibody fraction. Interlinear differences were revealed by each of the signs under study, this pointing to the role of genetic factors in the formation of antibodies to polysaccharide of group A streptococcus.