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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 685 records · Page 38Linked to original sources
PubMed1988

Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer-associated antigens by anti-idiotypic antibodies.

Previously we have reported on the production of two sets of human monoclonal antibodies reacting with mouse mammary tumor virus (MMTV) and human mammary tumor virus (HuMTV) cross-reacting antigens. B11 is a monoclonal IgG generated by the human-human hybridoma technique using axillary lymph node of breast cancer patients. 4.6/6 is a monoclonal IgG established by the mouse-human hybridoma procedure using peripheral blood lymphocytes of a healthy investigator working with the breast cancer cell line T47D which secretes HuMTV antigens. Two anti-idiotypic (Id) antibodies were produced by immunizing rabbits with B11 or 4.6/6. Following exhaustive adsorption on unrelated human-Ig, fetal calf serum and purification on B11 or 4.6/6 affinity columns, the anti-Id antibodies were shown to react specifically with their respective Id. The binding of these anti-Id antibodies to the respective Id was specifically inhibited by prior incubation of the Id with MMTV and/or HuMTV antigens. Rabbit anti-B11 and rabbit anti-4.6/6 anti-Id antibodies were employed to immunize female C3Heb mice. Following immunizations, humoral and cellular immune responses to MMTV-related antigens could be demonstrated. The sera of the mice contained anti-MMTV antibodies and delayed-type hypersensitivity was specifically expressed when irradiated cells of the Mm5MT line (which carry surface MMTV antigens) were injected. Our results support the notion that anti-Id antibodies harboring the internal image can immunize animals against tumor cells bearing on their surface viral-associated antigens.

Animals↗
PubMed1988

In vitro T-cell functions specific to an anti-DNA idiotype and serological markers in patients with systemic lupus erythematosus (SLE).

The human monoclonal autoantibody 16/6 is a common anti-DNA idiotype found to have clinical relevance in patients with systemic lupus erythematosus (SLE). Therefore the ability of peripheral blood T cells of SLE patients and healthy controls to proliferate and to produce helper T-cell factors following stimulation with this idiotype was tested. It was found that T cells of 75% of healthy donors proliferated to the 16/6 idiotype, whereas only 22% of SLE patients responded to this idiotype by proliferation. On the other hand, the capability to produce T-cell helper factors specific to the 16/6 idiotype was found in a higher percentage of SLE patients (48%) as compared to healthy controls (31%). The low frequency of proliferative responses in SLE patients might be due either to the chronic exposure to the 16/6 idiotype or to the production of antiidiotype antibodies against the 16/6 idiotype, which interfere with the response to the latter stimulator.

Adolescent↗
PubMed1988

Autoantibodies and common idiotypes in men and women with sperm antibodies.

Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.

Adult↗
PubMed1988

Autoimmune diseases other than lupus share common anti-DNA idiotypes.

We examined the sera of 170 patients with various autoimmune diseases other than systemic lupus erythematosus (SLE) for the presence of an anti-DNA antibody idiotype termed 16/6 and known to occur with high frequency in sera of patients with SLE. The idiotype was found in 6/15 sera from patients with polymyositis (49%), 3/18 with multiple sclerosis (17%), 3/18 with primary Sjögren's syndrome (18%), 9/40 with autoimmune thyroid diseases (23%), 2/35 with myasthenia gravis (6%), and 3/42 patients with rheumatoid arthritis (7%). The idiotype was not detected among 12 patients with scleroderma or 77 normal controls. The presence of the 16/6 idiotype was associated with the presence of another anti-DNA idiotype termed 134-Id. Serum samples were also tested for activity against DNA, various synthetic polynucleotides, and cardiolipin. The serum activity against these antigens was found to be polyspecific, though overlap in reaction against the various polynucleotides was not absolute. The 16/6 idiotype is thought to be coded by a germline gene. The presence of this idiotype in various autoimmune diseases points to a pathophysiologic link between the diseases.

Autoantibodies↗
PubMed1988

Naturally-occurring tumor-reactive autoantibodies: a monoclonal antibody from normal mice reacts with tumor cells and with DNA.

A natural IgM monoclonal antibody, 1.67, was generated from apparently healthy unstimulated BALB/c mice. This antibody reacted with L5178Y murine T cell lymphoma, with human Raji cells, and with several normal cells. Further analysis of its ligand binding capacity disclosed strong binding to single-stranded DNA (ssDNA). However, this naturally-occurring monoclonal antibody binds to different epitopes on cell membranes and on DNA than another anti-DNA monoclonal antibody (18/103/1) from human origin. This conclusion was based on competition assays. Furthermore, NOA 1.67 lacks the 16/6 idiotype expressed on the 18/103/1 antibody. The 16/6 idiotype is shared by human and mouse lupus monoclonal autoantibodies that bind simultaneously to lymphoid cells and DNA. This is a first report on a natural autoantibody that binds to malignant and to normal cell membrane(s) as well as to ssDNA. It may have regulatory functions controlling malignancy and or autoimmunity.

Animals↗
PubMed1988

A human monoclonal anti-DNA antibody derived from a patient with polymyositis having the common lupus 16/6 idiotype.

A human IgM monoclonal antibody (Pol-1, SA-1) was generated by the human hybridoma technique from the peripheral blood lymphocytes (PBL) of a patient with active polymyositis. The antibody was found to bind to ssDNA, dsDNA, poly(I) and poly(G) and to carry the common lupus anti-DNA antibody idiotype (16/6 Id). Another human IgM monoclonal antibody (Pol-2, SA-2) produced by similar methods from the PBL of the same patient while in remission lacked the ligand-binding capacities of Pol-1 SA-1 and did not have the 16/6 Id. Analyses of 19 sera samples from patients with polymyositis showed no antinuclear antibodies, excluding a 40% prevalence of the 16/6 Id. The serum of the patient whose lymphocytes were employed to generate the hybridoma was negative for anti-DNA activity as well as for the 16/6 Id. This study suggests that the hybridoma technique may enable expression of dormant idiotypic affinities which do not normally appear in sera.

Antibodies, Antinuclear↗
PubMed1988

Immunoglobulin secretion of mononuclear cells induced by various mitogens.

Immunosufficiency can be evaluated by Ig secretion subsequent to mitogenic stimulation of human mononuclear cells (MNC). It seems that there are significant differences in immunoglobulin class secreted by these cells when stimulated with various polyclonal activators. The aim of the current study was to analyse these differences. MNC cells was randomly obtained from nine healthy blood donors and were activated by Epstein-Barr virus (EBV), group-A streptococcus (A-ScM), Staphylococcus aureus (SAC), Klebsiella pneumonia (Kleb-M) and pokeweed mitogen (PWM). Significantly increased levels of IgM were recorded after a 7 day incubation followed by stimulation with Kleb-M (6.2 +/- 2.9) and EBV (5.9 +/- 4.5) compared to inactivated MNC (1.6 +/- 1.4), and following 10 days incubation then stimulation by EBV (13.4 +/- 5.5) and Kleb-M (9.9 +/- 4.2) compared to unstimulated cells (2.9 +/- 1.8). Significantly greater IgG levels were achieved following incubation with EBV (3.0 +/- 4.0) and PWM (2.4 +/- 1.3) after 7 days (vs 0.6 +/- 0.4 in unstimulated cells) and by PWM (11.7 +/- 5.3) and Kleb-M (8.8 +/- 3.9, vs 2.3 +/- 2.2) after 10 days. The present data emphasize the significance of merging both mitogen selection and culture duration for acquiring information and high fidelity results of immunoglobulin secretion by polyclonal activators.

B-Lymphocytes↗
PubMed1988

Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype.

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

Animals↗