[Some features of immunological status in young peoples irradiated in utero or in age up to 4 years as result of Chernobyl accident].

Some characteristics of immune system, namely quantities of serum immunoglobulins A, G, M and activity of free and hidden autoantibodies to DNA, cardiolipin and microsomal thyroid antigen were studied in young people irradiated in utero or in age up to 4 years through Chernobyl accident. The hallmarker of observed immunological changes is low content of immunoglobulin A. Degree of reduction was in back proportion with level 137Cs contamination inhabit territory. A lowering of the content of IgA in persons irradiated in utero depends on period of pregnancy at a moment of the accident: the most reduction was observed in young people irradiated in the first trimester of gestation. It was shown elevation of activity autoantibodies to cardiolipin. Both deficit of IgA and elevation activity the autoantibodies were observed only in proportion of young people irradiated in utero or in early period of life.

Natural hidden autoantibodies react with negatively charged carbohydrates and xenoantigen Bdi.

Immunoglobulin preparations from sera of healthy donors contain polyspecific autoantibodies interacting with DNA and other charged antigens. These antibodies belong to the IgG class and can exist in the free or hidden state. The hidden antibody activity can be revealed after ion-exchange chromatography on QAE-Sephadex A-50. Immunoenzyme assay was used to assess the interactions of both free and hidden antibodies with different carbohydrates. The hidden antibodies were only able to interact with different polyanionic carbohydrates and neutral xenoantigen Bdi.

Effect of natural antiphospholipid antibodies on antithrombotic activity of vascular wall.

Natural latent human antibodies cross-reacting with DNA and cardiolipin, interact with human endothelial cells, decrease antiaggregation activity of rat aortic wall, and increase fibrinolytic activity of the wall of the inferior vena cava. It is assumed that natural antiphospholipid antibodies present in immunoglobulin preparations in a latent state modify antithrombogenic activity of the vascular wall and are a potential cause of antiphospholipid syndrome.

Natural hidden antibodies reacting with DNA or cardiolipin bind to thymocytes and evoke their death.

Both free and hidden natural antibodies to DNA or cardiolipin were obtained from immunoglobulins of a normal donor. The free antibodies reacting with DNA or cardiolipin were isolated by means of affinity chromatography. Antibodies occurring in an hidden state were disengaged from the depleted immunoglobulins by ion-exchange chromatography and were then affinity-isolated on DNA or cardiolipin sorbents. We used flow cytometry to study the ability of free and hidden antibodies to bind to rat thymocytes. Simultaneously, plasma membrane integrity was tested by propidium iodide (PI) exclusion. The hidden antibodies reacted with 65.2 +/- 10.9% of the thymocytes and caused a fast plasma membrane disruption. Cells (28.7 +/- 7.1%) were stained with PI after incubation with the hidden antibodies for 1 h. The free antibodies bound to a very small fraction of the thymocytes and did not evoke death as compared to control without antibodies. The possible reason for the observed effects is difference in reactivity of the free and hidden antibodies to phospholipids. While free antibodies reacted preferentially with phosphotidylcholine, hidden antibodies reacted with cardiolipin and phosphotidylserine.

[Heterogeneity and avidity of autoantibodies reacting with DNA]. / Geterogennost' i avidnost' autoantitel, reagiruiushchikh s DNK.

Subpopulations of auto-antibodies to DNA were isolated by affinity procedures from sera of two patients with SLE and from IgG of healthy donors after ion-exchange chromatography ("hidden" auto-antibodies). It was found that two subpopulations of auto-antibodies are present in SLE sera just as fractions of "hidden" auto-antibodies consist of three subpopulations. The dissociation constants were measured by ELISA for the interaction of all subpopulations of auto-antibodies to DNA. It is shown that KD are very high and identical no matter of whether they were prepared from SLE sera of from IgG of healthy donors. The analogy of two types of auto-antibodies (SLE auto-antibodies and "hidden" auto-antibodies) is discussed in this paper.

["Masked" autoantibodies from the serum of healthy blood donors cross-reacting with DNA and bacterial lipopolysaccharides]. / "Skrytye" autoantitela iz syvorotki krovi zdorovykh donorov, perekrestno reagiruiushchie s DNK i bakterial'nymi lipopolisakharidami.

The "masked" autoantibodies with polyspecific activity were found in the serum of healthy donors. It is shown that these antibodies are able to react with antigens after the ion exchange chromatography with QAE-sephadex. It was found that these "masked" antibodies are able to cross-react with DNA and lipopolysaccharides of wide-spread species of bacteria. The possible role of these antibodies as in protection of organism from the external antigens as in the origin of autoimmune diseases is discussed.

[Interaction of immunoglobulins with charged biopolymers: significance in the regulation of humoral immunity]. / Vzaimodeistvie immunoglobulinov s zariazhennymi biopolimerami: znachenie v reguliatsii gumoral'nogo immuniteta.

When subjected to ion exchange chromatography on QAE-Sephadex A-50 or gel filtration of Sephadex G-200 under conditions that cause the dissociation of immune complexes at pH 4.05, immunoglobulins both from serum and its immunoglobulin fraction increase their interaction with charged antigens as native DNA and cardiolipin. Ion exchange chromatography also leads to the deaggregation of complexes. It was demonstrated that immunoglobulins bind DNA molecule through its F(ab)2 fragments. Based on data obtained, the suggestion was made that interaction between immunoglobulins and charged serum biopolymers is an important factor in humoral immunity regulation. Namely, high specificity of immunological reactions may be supported by elimination of non-specific binding provided electrostatic interactions from all the potential spectrum of antigen-antibody reactions.

[Effect of treatment with high doses of 6-methylprednisolone on the activity of anti-DNA antibodies and antiidiotypic activity in the sera of patients with systemic lupus erythematosus]. / Vliianie terapii udarnymi dozami 6-metilprednizolona na aktivnost' anti-DNK antitel i antiidiotipicheskuiu aktivnost' v syvorotkakh bol'nykh sistemnoi krasnoi volchankoi.

The effect of 6-methylprednisolone therapy at high doses on the time course of autoantibodies to DNA and anti-idiopathic (inhibitory) serum activity was studied in 22 patients suffering from SLE with a high clinicolaboratory activity. Pulse-therapy led to the improved status in 70% of the patients and rapid reduction of clinical and laboratory manifestations of disease (cerebrovasculitis, nephritis, skin involvement, etc.). Changes in clinicolaboratory findings well correlated with the time course of antibodies to DNA and the level of anti-idiopathic activity. This type of therapy was shown to result in a sharp reduction of antibodies to DNA and a parallel increase in idiopathic serum activity. Defining changes in idiopathic serum activity it is possible to determine therapeutic efficacy and to predict a further course of disease.

[Immunoglobulins acquire the ability to interact with DNA after chromatography on QAE-Sephadex]. / Immunoglobuliny priobretaiut sposobnost' vzaimodeistvovat' s DNK posle khromatografirovaniia na QAE-sefadekse.

The composition of IgG isolated from normal human serum includes a significant amount of antibodies interacting with native DNA. This ability of antibodies is revealed only after anion-exchange chromatography, resulting in the division of IgG into two fractions, i.e., acid and alkaline immunoglobulins. The peculiarities of interaction of the both fractions with DNA and the specificity of this reaction were investigated. The IgG tested were shown to interact with native and denaturated DNA, dextran sulfate, poly-G and poly-I. The possibility of interaction of antibodies with the charged structures of the cell and their significance under normal and pathological conditions are discussed.

[Immunological aspects of pulse therapy in systemic lupus erythematosus]. / Immunologicheskie aspekty pul's-terapii pri sistemnoi krasnoi volchanke.

Twenty SLE patients were examined against a background of pulse-therapy with methylprednisolone. The analysis showed that there was a decrease in the CIC concentration, antibodies to native DNA and an increase in the level of C3c and C4 components of the complement against a background of pulse-therapy. A more rapid time course of the CIC level was noted shortly after pulse-therapy as compared to changes in other immunological indices. A dynamic study of immunological indices in SLE against a background of pulse-therapy was appropriate for a clinical assessment and a study of the mechanisms responsible for the therapeutic efficacy of this method.

Biosynthesis and cytoplasmic distribution of small poly(A)-containing B2 RNA.

Previously, we described a small polyadenylated RNA predominantly located in cytoplasm and hybridizing with the ubiquitous B2 sequence of the mouse genome (Kramerov, D.A., Lekakh, I.V., Samarina, O.P. and Ryskov, A.P. (1982) Nucleic Acids Res. 10, 7477-7491). This 180-300 nucleotide long RNA was designated B2 RNA. Here, we demonstrate that B2 RNA is complementary to just one of the strands of cloned B2 sequence. The synthesis of B2 is rather resistant to ultraviolet irradiation of Ehrlich ascites carcinoma cells. The treatment of the cells with alpha-amanitin at a concentration completely blocking the formation of small nuclear RNAs U1, U2 and U3 does not interfere with the B2 RNA synthesis. These results suggest that B2 RNA formation is directly transcribed with the aid of RNA polymerase III, rather than being formed in the course of the processing of large RNA molecules which are known to contain a lot of B2 sequences. We also surprisingly found that the synthesis of up to 50% of long poly(A) +RNA in Ehrlich carcinoma cells is rather resistant to alpha-amanitin. The possible role of genetic elements including B2 sequences able to promote large RNA-polymerase III transcripts is discussed. B2 RNA in the cytoplasm is incorporated into the ribonucleoprotein particles, both small (12-18 S) and heavy. The latter probably correspond to informosomes. After deproteinization of heavy particles, a major part of B2 RNA still cosediments with mRNA and is split from it only after denaturation. We suggest that the B2 RNA of heavy ribonucleoproteins is associated with mRNA by short complementary stretches. About half of the B2 RNA is recovered in the cytoskeletal fraction. The possible role of B2 RNA in mRNA transport or in translation regulation is discussed.

[Clinico-immunological characteristics of systemic lupus erythematosus with Raynaud and Sjögren's syndromes (report I)]. / Kliniko-immunologicheskaia kharakteristika sistemnoi krasnoi volchanki s sindromami Reino i Shergena (soobshchenie I).

Forty-one patients suffering from chronic systemic lupus erythematosus with Raynaud and Sjögren's syndromes and 18 patients with an acute and subacute disease course were examined. It was established that chronic SLE was marked by a high frequency of antibodies to ribonucleoprotein, an increase in the concentration of IgA, the presence of rheumatoid factor. Although the decrease in the concentration of C3c and C4 components of complement was more demonstrable in patients with an acute or subacute course of SLE, the rate of demonstration of circulating immune complexes in the patients' groups under comparison was approximately the same. Involvement of immune complexes in the development of the pathological process in different versions of SLE is discussed.

[Nuclear and cytoplasmic RNA showing hybridization with repetitive sequences B1 and B2 of the mouse genome]. / Iadernye i tsitoplazmaticheskie RNK, gibridiziruiushchiesia s povtoriaiushchimisia posledovatel'nostiami B1 i B2 genoma myshi.

Heavy nuclear RNA contains high amounts of transcripts from repetitive sequences B1 and B2. Cytoplasmic poly(A+)RNA and in particular, polysomal poly(A)+RNA (mRNA) also contain these sequences though their content is much lower. An abundant 2 kb mRNA of mouse liver was found to contain B2 sequence. A novel class of RNA is described namely as low molecular weight heterogeneous (200-400 nucleotide long) poly(A)+RNA. These RNAs contain B1 and B2 sequences and are located mostly in the cytoplasm but not in polysomes. Tumor cells contain high amounts of small B2+RNAs. The content of B1+ small cytoplasmic RNA is much lower. The hybridization tests confirm the existence of extended homology between B1 sequence and 4.5 S small nuclear RNA which has been earlier deduced from comparison of their base sequences. Homology of B1 and small cytoplasmic 7S RNA was also detected. No hybridization of B2 to small nuclear or small cytoplasmic RNAs could be detected.

The sequences homologous to major interspersed repeats B1 and B2 of mouse genome are present in mRNA and small cytoplasmic poly(A) + RNA.

Heavy nuclear RNA contains high amounts of transcripts from repetitive sequences B1 and B2. Cytoplasmic poly(A)+RNA and, particularly, polysomal poly(A)+RNA (mRNA) also include these sequences but in smaller amounts. The abundant 2 kb mRNA of mouse liver are found to have a B2 sequence. These sequences are also found in a new class of low-molecular-weight heterogeneous (200-400 nucleotide long) poly(A)+RNAs. These RNAs are located mostly in cytoplasm rather than in polysomes. The amount of small B2+ RNAs is noticeable larger than that of small B1+ RNAs. Tumour cells seem to contain more small B2 RNA than normal cells. The hybridization tests show that extended homology exists between the B1 sequence and 4.5S small nuclear RNA, which is predicted from comparison of their base sequences. Also, we have found homology between B1 and small cytoplasmic 7S RNA. Hybridization of B2 to sn or sc RNAs has not been observed, although the sequencing reveals partial homology between B2 and 4.5S sn RNAI /1/.