[The specific features of the immunophenotype of blast cells in patients with de novo normal karyotype acute myeloid leukemia and FLT3-ITD mutation].

AIM: To study the specific features of de novo acute myeloid leukemia (AML) with FLT3-ITD mutation. SUBJECTS AND METHODS: The results of examination were analyzed in 101 patients. Bone marrow morphological specimens were stained with Pappenheim stain. The karyotype was investigated using the standard GTG-banding method. Blast cells were immunotyped in a five-color analysis on a Cytomics FC 500 laser flow cytofluorometer. RESULTS: FLT3-ITD mutation was identified in 21 patients who had a varying morphological nature of blasts, different karyotype variants, and frequently additional NPM1 gene mutation. The distinctive property of 10 patients with normal karyotype and FLT3-ITD mutation (without NPM1 gene mutation) was the larger number of cases with high expression of HLA-DR and CD7 than in the control group that included 18 patients with normal karyotype AML without FLT3-ITD nutation: 50% versus 6.2% (p = 0.007) and 100% versus 55.6% (p = 0.014), respectively. CONCLUSION: Normal karyotype AML with FLT3-ITD mutation is a group that is homogeneous in the biological phenotype of leukemia cells.

16(th) IHIW: population global distribution of killer immunoglobulin-like receptor (KIR) and ligands.

In the last fifteen years, published reports have described KIR gene-content frequency distributions in more than 120 populations worldwide. However, there have been limited studies examining these data in aggregate to detect overall patterns of variation at regional and global levels. Here, we present a summary of the collection of KIR gene-content data for 105 worldwide populations collected as part of the 15th and 16th International Histocompatibility and Immunogenetics Workshops, and preliminary results for data analysis.

[Clinical significance of lymphocyte subpopulations and cytokine-producing activity of blood cells in patients with primary myelodysplastic syndrome].

Lymphocyte subpopulation composition and spontaneous production of tumor necrosis factor-alpha (TNF-alpha) by blood cells were studied in 22 and 15 patients with myelodysplastic syndrome (MDS), respectively, who were under immunosuppressive therapy (IST). Patients with hematological response revealed a significantly increased cytotoxic CD8+ lymphocyte concentration and TNF-alpha production. A direct correlation between TNF-alpha production rate and CD8+ lymphocyte level was established. Maximum cytokine-producing activity of blood cells was identified in MDS patients with enhanced erythroid response. The study established a great diversity of MDS, its hypoplastic variants and the prognostic value of spontaneous production of tumor necrosis factor-alpha (TNF-alpha) by blood cells as marker of IST efficacy.

[Immunomodulator Cycloferon in the comprehensive treatment of patients with acute non-lymphoblastic leukemia]. / Immunomoduliator tsikloferon v kompleksnom lechenii bol'nykh ostrimy nelimfoblastichnymi leikozami.

The therapeutic benefit and action of the immunomodulator Cycloferon were evaluated in patients with acute non-lymphoblastic leukemia. When administered in conjunction with chemotherapy during first complete remission, it reduced both early-onset relapse frequency and degree of cytostatic-induced immune deficiency. The drug's action is mediated by changes taking place in cytokine and interferon synthesis.

[Prognostic value of some biochemical and immunologic factors in the management of multiple myeloma]. / Prognosticheskaia tsennost' nekotorykh biokhimicheskikh i immunologicheskikh faktorov pri mnozhestvennoi mielome.

The results of examination of 58 patients in the course of multiple myeloma (MM) are discussed. Prognosis for LDH, beta2-m and FNO-alpha administration was evaluated versus immunochemical pattern, tumor mass and response to different chemotherapeutic regimens. High prognostic value of serum levels of LDH, beta2 and FNO-alpha in MM patients was observed. The method may be useful in carrying out chemotherapy and detecting recurrences and chemoresistance.

[The results of a hematological examination of the population living in an area of intense radiological control in Bryansk Province]. / Rezul'taty gematologicheskogo obsledovaniia naseleniia, prozhivaiushchego v zone usilennogo radiatsionnogo kontrolia Brianskoi oblasti.

As many as 1492 residents of populated areas in Zlynka District of Bryansk Province were studied. There were 628 children and 864 adults in the series. Contamination with radionuclides in the territory of residence was of the order of 40/km2 and above; the level of cesium deposition in the body of the examinees ranged between 0.4 to 3.4. Deviations from the norm in the peripheral blood were detected in 15% of adults and 36% of children. These were manifest by hypochromic anemia, by eosinophil- and lymphoid-type leukemoid reactions, and by other disorders that resulted from nutritional imbalance, deficiency of iron of varying genesis, helminthic invasion, allergic states. Concurrent cellular and humoral immunity shifts coupled with the deviations from the norm in the indices for the thioldisulphide system attest to the need for designing of measures to secure long term observation over health state of the population residing in the contaminated territories.

[The HLA phenotype and duodenal ulcers in patients following kidney transplantation]. / HLA-fenotip i duodenal'nye iazvy u bol'nykh posle transplantatsii pochki.

The authors have performed an investigation of the association between ulcer disease of the duodenum and bleedings from the ulcers in 204 patients after transplantations of the kidney with the antigen of HLA system histocompatibility. Duodenal ulcers were found in 25 patients (12.9%), in 11 of them the ulcers were complicated by bleedings which was 5.4% of the total number of the patients with the transplanted kidney. The evaluation of the HLA antigen distribution has revealed an association of duodenal ulcers with A2 and B13 antigens which took place significantly more often than in a group of practically healthy people (RR = 1.85 and 1.9 correspondingly). In patients with the transplanted kidney and following ulcerous bleedings this association was more obvious (RR = 2.32 and 3.74 correspondingly). According to the calculated etiological fraction 40% of the patients can be supposed to have the etiological association of the disease with A2 antigen and 20% of the patients with B13 antigen. A typical feature was the presence of possible "protective" A9 antigen which was found in the group under study two times more seldom than in the control group (RR = 0.25). A comparison of the distribution of HLA antigens in the patients in whom there developed bleeding duodenal ulcers with those who had no such complications has also established the association of the disease with HLA A2 and B13 antigens. The probable "protective" A9 antigen was also found. Since the kidney transplantation is preceded by determination of the recipient's HLA phenotype, these data can be used as prognostic criteria as well as the indications to performing preventive antiulcerous therapy in patients with high risk of the development of ulcerous lesions of the gastrointestinal tract.

[Immunologic monitoring and immune reconstitution in recipients of allogeneic bone marrow]. / [Immunomonitoring i immunorekonstitutsiia retsipientov allogennogo kostnogo mozga]

The dynamics of different peripheral blood lymphocyte subpopulations (CD3+, CD4+, CD8+, CD22+, DR+, CD25+ and CD16+) and levels of serum cytokines TNFa and IL1 beta were evaluated in 10 patients with allogeneic bone marrow transplantation (BMT). It was established that initially low levels of practically all the lymphoid subsets studied came back to normal in patients with favorable post-BMT course, while, in unfavorable post-BMT course (GVHD or relapse), the levels of said lymphoid subsets remained unchanged or even dropped. Post-BMT increase in serum TN alpha level can be of prognostic value for GVHD development whereas serum IL1 beta level does not correlate with post-BMT course.

[Development of a method of obtaining lyophilized antileukocyte histotyping sera intended for long-term storage]. / Razrabotka metoda polucheniia sukhikh antileikotsitarnykh gistotipiruiushchikh syvorotok s tsel'iu ikh dolgosrochnogo khraneniia.

An optimal scheme for sublimation of anti-HLA-sera of locuses A, B, C, and DR has been developed, consisting of freezing at 60 degrees C and lyophilization to 29-30 degrees C, this permitting the preparation of initially active antileukocytic sera. The activity and specificity of defrosted native and lyophilized anti-HLA-sera were assessed in the complement-dependent cytotoxicity test. Four-year follow-up of the activity of dried anti-HLA-sera showed that the stabilizer was not needed, for the activities of the sera lyophilized with and without it was virtually equally high. The optimal storage temperature for dry anti-HLA-sera is 4 degrees C.

[A granulopoiesis inhibitor. Synthesis and biological activity]. / Ingibitor granulopoéza. Sintez i biologicheskaia aktivnost'.

Three schemes of synthesis for pentapeptide Glp-Glu-Asp-Cys-Lys-OH were compared was carried out. Acetamidomethyl protection was used for the mercapto group of cysteine. For the same purpose, cystine was used as the starting compound for synthesis. The optimal method was shown to be the solid phase method with S-acetamidomethyl cysteine protection that can be removed by mercuric acetate before the cleavage of a peptide from a polymer. The stabilized peptide inhibits proliferation of bone marrow cells of patients with chronic myeloleukemia 5- to 20-fold and has a less pronounced effect (up to 2-fold inhibition) on peripheral blood cells. Thus, its application for the therapy of hemoblastoses is promising.

[Optimized recording of results of the lymphocytotoxicity test using a luminescent attachment to Biolam-P-I microscope]. / Optimiziirovannyi uchet rezul'tatov limfotsitotoksicheskogo testa s pomoshch'iu liuminestsentnoi nasadki k mikroskopu "Biolam-P-I".

The fluorescent attachment appreciably simplifies the procedure of recording the results of the lymphocytotoxic test, is compact, economic, and easily inserted in the Biolam-P-I inverted microscope. Use of fluorescent stains helps selectively stain viable and intoxicated cells, thus simplifying their estimation. The said modification may be used in HLA typing and assessment of the principal lymphocyte subpopulations in the peripheral blood.

[Class I histocompatibility antigens as markers of human susceptibility to influenza A viruses]. / Antigeny gistosovmestimosti klassa I kak markery vospriimchivosti chelovecheskogo organizma k virusam grippa A.

The results of many years' studies of HLA-phenotypes in human beings with various susceptibility to influenza infection are presented. Some histocompatibility class I antigens are revealed to correlate moderately with the risk of reinfection and the recurrent course of influenza, as well as with the severity of pulmonary complications and with the inclination of a macroorganism to the latent carriage of viral proteins. The specific features of a humoral immune response to vaccination with attenuated influenza viruses in human beings with HLA-B8 are demonstrated. The authors indicate that there is a trend towards less pronounced manifestations of influenza infection in individuals with antigen-markers A9, B40, characteristic of a Mongoloid population, which might be related to the origin of influenza viruses.

[An analysis of DNA reparative synthesis in the lymphocytes of bronchial asthma patients]. / Analiz reparativnogo sinteza DNK v limfotsitakh bol'nykh bronkhial'noi astmoi.

Spontaneous and UV-stimulated unschedule syntheses (US) of DNA in the peripheral blood lymphocytes and HLA antigens were investigated for asthmatic patients. The index of stimulation (IS) of DNA repair was determined as the ratio of the values of UV-stimulated US to spontaneous US. In the patients, a significant elevation of the intensity of spontaneous DNA US and the decrease in IS values were revealed as compared with the healthy controls. At the same time the intensity of UV-stimulated IS did not differ in patients and the control subjects. The values of IS appeared to be significantly higher in those patients who had the HLA-Al antigen in their phenotype compared to those who had not. Possible mechanisms for the alteration of the DNA repair capacity of lymphocytes and for the relationship between cytogenetic damages and immunogenetic features in asthmatic patients are discussed.

[Morphological and pathogenetic aspects of aplastic anemia]. / Morfologicheskie i patogeneticheskie aspekty aplasticheskoi anemii.

A complex study of colony-stimulating properties of cells-precursors of granulomonocytopoiesis, morphological parameters of the marrow histological structures and immunological parameters was carried out in 90 patients to specify pathogenic mechanisms of aplastic anemia (AA) development. 95% of patients appeared to have sharp decrease of the marrow colony-stimulating properties and only 5% had normal initial indexes. In most patients endostal cell number increased, while the content of reticulocytes grew higher in more than 30% of patients. Defect of the marrow stroma functioning was registered in 23% of patients. Increase of the osseous tissue volume and osteocyte number was found. Dysbalance in cellular link of immunity was demonstrated. Only temporal increase of the marrow colony-stimulating properties was marked in some patients on the background of treatment with antilymphocyte globulin, despite the clinic-hematological improvement. Multifactor pathophysiological mechanisms, the main of which is the stem cell defect lies in the base of AA pathogenesis. Hemopoietic microenvironment pathology is not the leading reason of the hemopoiesis depression but it contributes greatly in its development. Immunological alterations in patients with AA are secondary and can be partly corrected with treatment with ALG.

[The association of HLA antigens with gastric and duodenal peptic ulcer]. / Assotsiatsiia antigenov sistemy HLA s iazvennoi bolezn'iu zheludka i dvenadtsatiperstnoi kishki.

The association of duodenal ulcers with antigens AIO and combinations of antigens B18B40, B35B40, A10B5, A10B40 and others and the association of gastric ulcer with antigens A3B7, A3B40, B14B15 were revealed by an investigation of HLA antigens in 46 patients with ulcer disease of the duodenum and 25 patients with ulcer disease of the stomach. It was concluded that the ulcer disease had a hereditary predisposition characterized by genetic heterogeneity with different etiopathogenetic mechanisms of the development of ulcers of different localizations. The HLA antigens may be used as immunogenic markers of ulcer disease if observing the population method in the investigations.

[Distribution of alleles of DRB, DQB and DQA loci of major histocompatibility complex in healthy donors of Saint Peterburg]. / Osobennosti raspredeleniia allelei lokusov DRB, DQB i DQA glavnogo kompleksa gistosovmestimosti u zdorovykh donorov Sankt-Peterburga.

The distribution of alleles of DRB, DQB and DQA loci was investigated in 118 healthy donors from St. Petersburg. Said alleles were identified by the restriction fragment length polymorphism method using DRB, DQB and DQA probes after TaqI digestion and Southern blotting. The frequencies of said alleles were compared with those of a cohort of healthy donors living in Germany. A significantly higher frequency of DRB-17-2 was identified in the Russian donors, as compared with the German counterparts. Also, the Russian donors revealed a decrease in the frequency of DQB-1 (P = 0.01) and an increase in that of DQB-X allele (P = 0.05). An analysis of DRB, DQB and DQA locus a alleles adhesion in a sample of donors from St. Petersburg showed it to agree, in a large proportion of cases, with the literature data. A parallel study of immunological specificity of DR antigen was undertaken to compare the results of genetic and serologic typing; errors in DR specificity identification were found to have been made in 17.0%.

HLA antigens in borderline and essential hypertension.

The subject of investigation was the comparison of HLA antigen distribution in people with borderline hypertension (BH) and essential hypertension (EH). One hundred twenty-one men with BH and 60 men with EH were studied. The HLA frequency was compared with that in 858 healthy men, who were blood donors. In BH the increase of B16, B18, and Cw4 and the decrease of A11 and B5 antigen frequency were found. In comparison with St. Petersburg's healthy population, patients with EH were characterized by increasing antigens B18, B41, Cw2, and Cw4 frequency. The coincidence of increased antigen B18 and Cw4 representation in BH and EH allows us to consider them to be immunogenetic markers or predictors of development of EH.