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Biomedical subjects

A Ruíz-Argüelles

Publications and source records attributed to A Ruíz-Argüelles.

11 recordsLinked to original sources
PubMed1998

Penetration of anti-DNA antibodies into immature live cells.

Several data suggest that immature lymphoid cells are more prone to penetration and therefore are affected more by antibodies than their mature counterparts. In this study, we examined the penetration of monoclonal anti-DNA antibodies in several models of immature cells. Results confirm that most anti-DNA antibodies penetrate larger proportions of immature cells than normal adult cells. It was also proven that anti-DNA antibodies induce larger fractions of immature cells to undergo apoptosis than mature cells; however, there is not a numerical association between penetration and apoptosis. Additionally, the penetration and induction of apoptosis of several anti-DNA monoclonal antibodies into U937 and NIH-3T3 cells followed a rather heterogeneous pattern. When mature and immature cells were stimulated polyclonally, it was shown that polyreactive antibodies might act as an accessory signal to induce apoptosis in immature cells. This process could contribute to the edition of the immune repertoire. We propose that naturally occurring polyreactive antinuclear antibodies, through penetration and deletion of self-reacting cells, could participate, either as a unique or secondary signal, in the mechanism of self tolerance. If these polyreactive antibodies undergo affinity maturation, it is possible they may develop into pathogenic antibodies.

3T3 Cells↗
PubMed1998

Penetrating anti-DNA monoclonal antibodies induce activation of human peripheral blood mononuclear cells.

Different studies have shown that some autoantibodies are able to penetrate into living cells and that this phenomenon has functional consequences, including apoptosis. We have explored the effect of anti-DNA antibodies (Ab) on the in vitro activation of peripheral blood mononuclear cells (PBMNC) and found that a human polyclonal anti-DNA, IgG, which efficiently penetrated living cells, was able to induce the expression of different cell activation antigens in vitro such as CD69, CD71 or CD98 by PBMNC from normal individuals. However, the cell activation phenotype induced by anti-DNA Ab was considered anomalous since the expression of some activation antigens was not up-regulated, and others showed aberrant behaviour (such as down-regulation of ICAM-1 expression). Similar results were obtained using different murine anti-DNA monoclonal antibodies (mAb). In addition, mAb that showed an efficient ability to penetrate living cells tended to have a greater effect on PBMNC activation. Anti-DNA Ab were also able to induce a noticeable expression of CD95/Fas. These data indicate that penetrating anti-DNA Ab are able to induce an anomalous activation state in vitro in a significant fraction of PBMNC. We believe this effect may occur in vivoand could have an important function in the pathogenesis of the immune dysregulation seen in SLE.

Animals↗
PubMed1996

The penetration of autoantibodies into cells may induce tolerance to self by apoptosis of autoreactive lymphocytes and cause autoimmune disease by dysregulation and/or cell damage.

Autoantibodies to intracellular constituents often occur naturally. This would be difficult to understand were they unable to penetrate live cells, as was once generally accepted; however, they can and in so doing may alter cell functions, cause damage and even kill cells by apoptosis. Different autoantibodies have different effects and in this paper, further to our previous report on the penetration of anti-DNA, the penetration of anti-RNP, which may be a possible cause of apoptosis, is demonstrated. Penetration of lymphocytes by autoantibodies may play a role in the causation of autoimmune disease, influencing immune regulation and causing cell damage either directly or through nucleosomal DNA release as a result of apoptosis. This, in turn, could also further promote antigen-driven production of anti-DNA. In addition, by causing apoptosis of autoreactive cell clones, natural autoantibodies could influence tolerance during development and also later in life, thus, paradoxically, helping prevent autoimmune disease.

Apoptosis↗
PubMed1991

Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome.

The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Antibody penetration into living cells. V. Interference between two fc gamma receptor-mediated functions: antibody penetration and antibody-dependent cellular cytotoxicity.

The same Fc gamma receptor appears to be shared for two important phenomena: antibody-dependent cellular cytotoxicity (ADCC) and antibody penetration into living cells. ADCC is inhibited through interaction with the Fc gamma receptor during the antibody penetration process, indicating that both mechanisms may modulate each other in vitro.

Adult↗
PubMed1979

PHA-induced cellular cytotoxicity. Inhibition by a nonimmunoglobulin factor present in sera from patients with active systemic lupus erythematosus.

Phytohemagglutinin-induced cellular cytotoxicity by normal mononuclear cells (MNC) is inhibited by serum of patients with active untreated systemic lupus erythematosus (SLE) but not by that of patients with untreated inactive SLE or rheumatoid arthritis. Three-hour preincubation of normal MNC with SLE sera suffices to inhibit throughout the assay. Preincubation with phytohemagglutinin (PHA) before addition of sera does not prevent the inhibition. DEAE-cellulose chromatography, Sephadex G-200 fractionation and immunoelectrophoretic analysis have shown the nonimmunoglobulin nature of this factor. It is thermostable and not affected by deoxyribonuclease or ribonuclease treatment. The mitogen-induced cellular cytotoxicity-inhibiting factor seems to be independent of other serum factors capable of blocking PHA-induced blastogenic transformation.

Arthritis, Rheumatoid↗
PubMed1979

Antibody penetration into living cells. I. Intranuclear immunoglobulin in peripheral blood mononuclear cells in mixed connective tissue disease and systemic lupus erythematosus.

We have shown recently (Alarcón-Segovia, Ruíz-Argüelles & Fishbein, 1978) that an IgG anti-RNP antibody obtained from a patient with mixed connective tissue disease (MCTD) can penetrate viable mononuclear cells (MNC) from normal donors via their Fc receptors. Live MNC from twelve MCTD patients incubated with goat anti-Ig antibody had intranuclear antibody with a speckled pattern in a mean of 5.5% of all MNC and 57.3% of all Fc receptor-bearing MNC. We found intranuclear immunoglobulins in all twelve patients with MCTD which were present only in cells with Fc receptors. Only three out of twenty-one patients with systemic lupus erythematosus (SLE) were found to have intranuclear antibody in a mean of 17.2% of their Fc receptor-bearing cells. Further experiments with MNC from SLE patients revealed a partial blocking of penetration of antibody via Fc receptors. MNC from ten scleroderma, ten rheumatoid arthritis patients and eleven normal controls did not have intranuclear immunoglobulin. In vivo penetration of autoantibodies into Fc receptor-bearing cells in MCTD, and probably in SLE as well, may represent an important pathogenetic mechanism.

Arthritis, Rheumatoid↗
PubMed1978

Decreased circulating thymus-derived cells with receptors for the Fc portion of immunoglobulin G in systemic lupus erythematosus.

Thymus-derived cells with receptors for the Fc portion of immunoglobulin G (Fcgamma+ T cells) have recently been found to have a suppressor function, a function that is decreased in systemic lupus erythematosus (SLE). Fcgamma+ T cells were found significantly diminished in 21 untreated SLE patients, particularly in the 7 patients who had active disease. Most Fcgamma+ T cells were separated with a subpopulation of T cells with low affinity for sheep erythrocytes. Decrease of this subpopulation was dependent on the decrease in Fcgamma+ T cells. Non-T cells with Fcgamma receptors were also diminished in SLE patients, but their decrease did not correlate with disease activity. The decrease in suppressor-cell function in SLE may be a result of loss, rather than of dysfunction, of the suppressor Fcgamma+ T cells.

Antibodies↗