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Biomedical subjects

N I Abdou

Publications and source records attributed to N I Abdou.

At least 73 records · Page 4Linked to original sources
PubMed1981

Cold dependent activation of complement in systemic lupus erythematosus. A unique cause for a discrepancy between clinical and laboratory parameters.

A 31-year-old woman with systemic lupus erythematosus (SLE) was studied because she developed markedly reduced total hemolytic complement activity at a time when her disease was clinically inactive. Functional assays demonstrated reduced activities of C1, C4, and C2, but normal concentrations of C3 and the terminal (C5-9) components were present. Antigenic concentrations of C1, C4, and C2 were normal. Plasma or serum obtained from blood allowed to clot at 37 degrees C had normal complement activity. Complement activity was depleted when the patient's serum was incubated in the cold. At reduced temperatures, the patient's serum (or purified IgG) depleted complement activity of normal human sera. A second patient with SLE was also demonstrated to have this same phenomenon. Cryoglobulins were not detectable in these patients. These data indicate that in vivo the patients' complement was normal and that the observed in vitro reduction was caused by cold dependent activation of the classical pathway.

Adolescent↗
PubMed1981

Immunoregulatory T-cell dysfunction in polyclonal gammopathy.

The mechanisms responsible for the increased serum immunoglobulines in polyclonal gammopathy states are unknown. We have studied the regulation of peripheral blood B-cell immunoglobulin synthesis and secretion, by T cells of either blood or bone marrow compartments, in 20 patients with polyclonal gammopathy and 27 controls with normal serum immunoglobulin levels. When compared to B-T-cell cocultures of normals, cocultures of polyclonal gammopathy patients had significantly higher levels of immunoglobulin secretion (P less than 0.01). Normal T cells but not T cells from patients with polyclonal gammopathy suppressed B-cell immunoglobulin secretion (P less than 0.01) and not the number of cytoplasmic immunoglobulin-positive cells of the polyclonal gammopathy patients. T cells from patients with polyclonal gammopathy enhanced normal B-cell immunoglobulin secretion (P less than 0.05) but not the number of cytoplasmic immunoglobulin-positive cells. Controls' bone marrow T cells were more efficient than blood T cells in suppressing polyclonal gammopathy B cells (P less than 0.02). T cells in polyclonal gammopathy are predominantly helper cells and could play a role in the enhanced immunoglobulin secretion of B cells. Bone marrow T cells are more efficient than blood T cells in regulating B cells. It seems that T cells predominantly regulate B-cell immunoglobulin secretion and not the number of B cells with cytoplasmic Ig.

B-Lymphocytes↗
PubMed1981

Modulation of the in vitro lymphocyte response by rabbit blastocysts.

Modulation by preimplantation (day 6 post coitum) rabbit blastocysts or by blastocoel fluid of the phytohemagglutinin (PHA)-stimulated autologous splenocytes as well as mixed leukocyte cultures (MLC) of rabbit allogenic splenocytes in vitro was studied. Results showed that in the absence of the blastocyst or blastocoel fluid, specific incorporation (S.I.) of PHA activated cultures was 7.11 +/- 1.19 (mean +/- S.E., n = 11), whereas the addition of 1 (n = 9), 2 (n = 8) or 3 (n = 7) blastocysts significantly (P less than 0.001) reduced the S.I. (0.56 +/- 0.09, 0.47 +/- 0.09 and 0.27 +/- 0.05, respectively). In the absence of the blastocysts or blastocoel fluid, 3057 +/- 1763 cpm were recorded as MLC response; the addition of 1 or 3 blastocysts showed 83 and 87% suppression, respectively (n = 11, P less than 0.001). The addition of blastocoel fluid also suppressed PHA or MLC responses (P less than 0.05). The effect was not due to the crowding or cytotoxic effects induced by the blastocysts in the cocultures, since spleen cell viability was greater than 89%. Rabbit blastocysts around the time of implantation have a great capacity of modulating PHA-induced splenocyte proliferative as well as allogenic recognition in vitro.

Animals↗
PubMed1981

Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus.

Regulation of serum anti-DNA antibody in systemic lupus erythematosus (SLE) by an antiidiotypic antibody was evaluated. Various sera from SLE patients in active and inactive states of their disease, as well as sera from normal individuals, were first completely depleted of anti-DNA and of DNA by affinity chromatography. The suppressive capacity of equimolar concentrations of the various depleted sera (blocking sera) on target lupus sera were determined. The target sera were from lupus patients with known DNA-binding capacity. Blocking sera from inactive SLE suppressed the binding of autologous anti-DNA antibody to [(3)H]DNA (n = 19,P < 0.01). Blocking sera from active SLE (n = 19), as well as human serum albumin, did not suppress. Sera from normal donors who had no contact with lupus patients or with lupus sera did not suppress (n = 14, P > 0.5), whereas those from normal donors who had contact with lupus patients or sera did suppress the binding (n = 5,P < 0.02). The anti-anti-DNA antibody suppressive activity in the inactive lupus serum was shown to be localized within the F(ab')(2) portion of immunoglobulin (Ig)G and could not be removed upon adsorption by normal human gammaglobulin. Furthermore, immune complexes could be detected by a Clq binding assay when the inactive lupus blocking sera were incubated with the anti-DNA antibody containing target sera. The specificity of the suppressive serum factor was shown by its inability to block the binding of tetanus toxoid to antitetanus antibody and its ability to block the binding of DNA to F(ab')(2) fragments of active lupus IgG. Regulation of serum anti-DNA antibody levels by anti-antibodies could induce and maintain disease remission in lupus patients and prevent disease expression in normals.

Antibodies, Antinuclear↗
PubMed1981

Heterogeneity of pathogenetic mechanisms in aplastic anemia. Efficacy of therapy based on in-vitro results.

The mechanisms responsible for the bone marrow failure in 21 aplastic anemia patients were studied by the colony-forming units in culture assay (CFU-C). Twelve patients had no detectable in-vitro defect that could be responsible for the low CFU-C numbers. Three patients had suppressor T cells that inhibited CFU-C (p less than 0.001); one of two patients responded to antithymocyte globulin therapy and the third recovered spontaneously. Three patients had serum inhibitory immunoglobulins directed against their marrow CFU-C; plasmapheresis resulted in recovery of bone marrow function. Three patients had abnormalities at the colony-stimulating factor level: Two had inhibitors of colony-stimulating factor, corrected in vitro and in vivo by indomethacin and cholinergic agonists (p less than 0.01); and the third had colony-stimulating factor generation defect, corrected in vitro and in vivo by lithium. Testing for cellular or humoral suppressor factors directed against precursor cells or for abnormalities at the colony-stimulating factor level gives helpful guidelines to therapy in aplastic anemia.

Adolescent↗
PubMed1980

Suppressor T cells in tolerance to deaggregated horse anti-human thymocyte globulin in man.

To understand the mechanism by which deaggregated horse anti-human thymocyte globulin (dATG) fails to induce untoward immunological reactions in man, three patients who received ATG and two patients who received dATG were studied for evidence of sensitization or tolerance to the foreign globulin. The ATG but not the dATG recipients developed allergic or serum sickness reactions; antihorse serum antibody could be detected in their serum and their blood cells proliferated in vitro in the presence of horse serum and secreted antihorse serum antibodies (P less than 0.001). Tolerance of the dATG recipients was shown to be mediated by specific T suppressor cells that carry receptors for horse serum and could be detected in the blood of one patient, whom we have studied serially, 13 weeks after therapy. Deaggregated ATG does not induce allergic or serum sickness reactions. It induces tolerance to the foreign protein via the generation of specific short-lived suppressor cells.

Agglutination↗
PubMed1980

Immunoregulation abnormalities in familial Addison's disease.

Three brothers, two with Addison's disease and a monozygous twin discordant for adrenal insufficiency, presented an unique opportunity to evaluate the endocrine and immunological abnormalities associated with this disorder. None of the brothers had clinical evidence of other autoimmune disease. However, each of the twins had elevated titers of antihydroglobulin and antiparietal cell antibodies, and both Addisonian siblings had cytoplasmic islet cell antibodies. We evaluated the ability of nonspecific Concanavalin A-activated suppressor cells from all three siblings to inhibit immunoglobulin biosynthesis by pokeweed mitogen-stimulated B cells, cell proliferation by phytohemagglutinin-stimulated T cells, and the proliferative response of an allogenic mixed lymphocyte culture. In comparison to normal controls, suppressor cells from the Addisonian siblings were less efficient in inhibiting both B and T cell activities. The nonAddisoninan twin had a lesser degree of impaired suppressor cell function to the B and T cell targets. Suppressor cell activity, as measured by the ability to inhibit proliferation within the mixed lymphocyte culture, was normal in all three siblings. The relationship of suppressor cell dysfunction, genetic predisposition, and the expression of the autoimmune state are discussed.

Addison Disease↗
PubMed1979

Nonspecific suppressor cell function in atopic subjects.

The status of concanavalin A (Con A)--nonspecific suppressor cell function and histamine-receptor--carrying mononuclear cells in 19 allergic and 27 nonallergic individuals was investigated. No differences were detected between the two groups with respect to suppression by Con A--activated suppressor cells of polyvalent Ig biosynthesis, IgG secretion, or mitogen-induced proliferative responses. Histamine-receptor--carrying cells of the allergic subjects were numerically equal to those of the nonallergic subjects. Mononuclear cells from the allergic group, however, required a higher dose of histamine than did those for the nonallergic group to induce suppression in vitro (p less than 0.02 for 10(-4) M histamine and p less than 0.05 for 10(-3) M histamine). Plasma from the allergic group contained higher levels of histamine activity (p less than 0.05). Plasma from either allergic or normal groups did not affect histamine activity in vitro. There are no apparent functional abnormalities of antigen-nonspecific mononuclear cells in the allergic patients with respect to non--IgE-mediated in vitro parameters. The demonstrated dysfunction of histamine-receptor--carrying cells could be attributed to high levels of circulating histamine that could result in receptor modulation in vivo. More work is needed to clarify the status of antigen-nonspecific and antigen-specific suppressor cells that regulate IgE biosynthesis in allergic states.

Adolescent↗
PubMed1979

Suppressor-cell antibody in systemic lupus erythematosus. Possible mechanism for suppressor-cell dysfunction.

Circulating antibodies that could be responsible for the suppressor thymus-derived (T)-cell dysfunction in active systemic lupus erythematosus (SLE) were investigated. Sera from 14 active and inactive SLE patients were compared with a pool of 22 normal sera. All sera were adsorbed with a pool of normal platelets to exclude antihistocompatibility leukocyte antigen antibodies; with AB erythrocytes to exclude isohemagglutinins; and with a pool of normal bone marrow-derived (B) lymphocytes, monocytes, and neutrophils to deplete anti-B-cell antibodies, Fc-receptor antibodies, and antibodies directed against neutrophils or monocytes. Sera from active SLE patients were capable of inhibiting the activation of normal, blood lymphocytes by concanavalin A to become suppressor cells. The latter were assayed by coculturing the concanavalin A-activated cells with autologous lymphocytes, which were then activated with either phytohemagglutinin for proliferative response or with pokeweed mitogen for B-cell immunoglobulin (Ig) synthesis and secretion. Specific incorporation of cultures with phytohemagglutinin showed a value of 67+/-13 (mean+/-SD) for suppressor cells treated with adsorbed, active SLE sera. This value was significantly different (P < 0.001) from that of cells treated with the inactive SLE sera or with the pool of normal sera. Similar findings were seen with respect to the B-cell target parameters. Cytoplasmic Ig and IgG in supernates of cultures with pokeweed mitogen showed values of 17+/-5% and 717+/-134 ng/culture, respectively, for suppressor cells treated with the adsorbed, active SLE sera. This was significantly different from those treated with the inactive SLE sera or with the pool of normal sera. The antisuppressor-cell factor was shown to be IgG, complement independent, not cytotoxic, active at 37 degrees C and at room temperature, but not at 4 degrees C, and adsorbable with T cells. Suppressor T-cell antibody in sera of active SLE patients could be responsible for the observed suppressor T-cell dysfunction seen in active SLE. The mechanisms responsible for the induction of the antisuppressor-cell antibody are unknown.

Antibodies↗
PubMed1978

Aplastic anemia associated with bone marrow suppressor T-cell hyperactivity: successful treatment with antithymocyte globulin.

In five patients with idiopathic aplastic anemia, the colony-forming unit (CFU-c) assay was used to quantitate stem cells and test the possible presence of suppressor cells inhibiting bone marrow differentiation. All five marrows failed to form CFU-c. In one out of the five cases tested, coculture of the patient's marrow with normal marrow suppressed the latter to form CFU-c. Removal of T-cells from the patient's bone marrow freed the aplastic marrow to produce more colonies and, in the coculture study, abrogated its inhibitory activity on the normal bone marrow. Treatment of the patient with horse antihuman thymocyte globulin (ATG), improved the peripheral blood count and myelopoiesis. Furthermore, the aplastic marrow increased its colony forming capacity from less than 1% pre-ATG to 46% post-ATG of the normal control, and its inhibitory activity on the normal marrow was ablated. In selected cases of aplastic anemia, with evidence of T-suppressor cell hyperactivity, treatment with ATG may offer an alternative approach to bone-marrow transplantation.

Anemia, Aplastic↗
PubMed1978

Suppressor cell-mediated neutropenia in Felty's syndrome.

The mechanism of neutropenia in Felty's Syndrome (FS) was tested. The suppressor capacity of mononuclear cells from patients with FS on normal bone marrow granulopoiesis was tested by the in vitro colony forming unit in culture assay. Peripheral blood, bone marrow, and spleen cells from FS patients with marked neutropenia (less than 1,000 neutrophils/mm3) suppressed the colony forming unit in culture of normal bone marrow. Cells from rheumatoid arthritis patients without neutropenia, cells from patients with drug-induced neutropenia without rheumatoid arthritis, or plasma from FS patients failed to suppress the colony forming unit in culture. Though suppressor cells were predominantly thymus-derived (T) cells, monocytes were also effective in suppression. The suppressor efficiency of cells from the various compartments were spleen greater than bone marrow greater than peripheral blood. Splenectomy in FS transiently corrected the neutropenia and eliminated suppressor cell activity. Hyperactive suppressor cells may be responsible for the neutropenia in some patients with FS. Correction of neutropenia in these patients should be directed at modulating the suppressor cell subpopulation.

Adult↗
PubMed1978

Suppressor-cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction.

To characterize the cell(s) responsible for the suppressor-cell dysfunction in active systemic lupus erythematosus (SLE), we fractionated blood mononuclear cells into thymus-derived (T), bone marrow-derived (B), and monocyte-depleted populations. Various cell populations from active SLE, inactive SLE, or normals, were activated with Concanavalin A, washed, and then co-cultured with active SLE cells. Soluble immune response suppressor (SIRS) from culture supernates of the activated cells was also used for the possible correction of the suppressor-cell dysfunction. Suppression was tested by enumerating DNA-binding cells by radioautography and by quantitating anti-DNA antibody in culture supernates by radioimmunoassay; and immunoglobulin was tested in cells and supernates by the immunofluorescence and the immunofluor techniques, respectively. Except for the numbers of DNA-binding cells, which were not suppressed, all the other three parameters in co-cultures with cells from active SLE patients were suppressed by Concanavalin A-activated cells (P < 0.001), or by SIRS (P < 0.05) from normals or inactive SLE patients. Concanavalin A-activated autologous or allogeneic active SLE cells and nonactivated cells from active or inactive SLE failed to suppress the various B-cell functions. Nonactivated normal cells suppressed levels of anti-DNA and immunoglobulin in supernates (P < 0.05). In characterizing the cells responsible for the suppressor dysfunction, it was clear from the results that T cells responsive to Concanavalin A activation are deficient in active SLE and fail to generate SIRS. On the other hand, monocytes from active SLE patients are responsive to signals from the activated T cells of normals or inactive SLE donors. Because SIRS suppresses active SLE cells in vitro, it might be considered therapeutically for the in vivo modulation of SLE.

Concanavalin A↗