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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 541 records · Page 30Linked to original sources
PubMed1993

The complement system and systemic sclerosis.

Serum concentrations of the various complement components including the classical and the alternative pathways were determined in 58 control healthy subjects and 80 patients with systemic sclerosis (SSC). The mean concentrations of C1q, C2, C5, C6, C7, C9, and factor B were significantly increased in the SSC patients in comparison to controls, while the increases were not significant for C3 and C8. C4 was an exception in that the mean levels were found to be decreased, with 18 patients having levels < 65% of the mean normal value. Properdin was also found to be decreased, but not significantly. We found a similarity between the pattern of serum complement component concentrations in SSC patients and patients with primary biliary cirrhosis, two disorders frequently associated in the same patients. The significance of complement component patterns in these diseases is discussed.

Complement Activation↗
PubMed1993

The detection of antithyroglobulin activity in human serum monoclonal immunoglobulins (monoclonal gammopathies).

The sera of 159 patients with monoclonal gammopathies were examined for the presence of anti-thyroglobulin (Tg) activity. An enzyme-linked immunosorbent assay was employed. Thirty-one (19.5%) sera were found to bind Tg. The activity against Tg was further confirmed by using purified immunoglobulins and employing competition assays. The anti-Tg antibodies were found in the sera of patients with IgG, IgM and IgA gammopathies. Anti-Tg antibodies were more frequent among patients with IgG gammopathy. Autoantibodies to Tg are found in patients with Hashimoto's thyroiditis, Graves' disease and occasionally in patients with thyroid carcinoma. Natural autoantibodies directed against human Tg have been detected, as well, in healthy subjects. None of the patients in the present study whose serum was found to contain high titers of anti-Tg human monoclonal antibodies had any clinical or biochemical evidence of thyroid disease. Our results of a high incidence of anti-Tg activity in the sera of patients with monoclonal gammopathies support previous reports of autoantibody properties characteristic of these immunoglobulins.

Autoantibodies↗
PubMed1993

Prevention of fetal loss in experimental antiphospholipid syndrome by low-molecular-weight heparin.

OBJECTIVE: The purpose of this study was to compare the effectiveness of low-molecular-weight heparin with regular heparin in the prevention of fetal resorption in mice with the antiphospholipid syndrome. STUDY DESIGN: Antiphospholipid syndrome was passively induced in ICR mice by injecting them with anticardiolipin antibodies on the first day of pregnancy. Subsequently, these mice were treated with low-molecular-weight heparin in two different doses, with regular heparin, and with a placebo. On gestational day 17 the mice were killed by cervical dislocation, and the pregnancy outcome was evaluated. Statistical analysis was performed by means of a one-way analysis of variance using Bonferroni's t test. RESULTS: Treatment with low-molecular-weight heparin resulted in a resorption rate of 22.4% as opposed to 41.4% in mice with antiphospholipid syndrome that were given regular heparin and 51.7% in nontreated controls. CONCLUSION: We conclude that low-molecular-weight heparin can prevent fetal resorptions in mice with antiphospholipid syndrome.

Animals↗
PubMed1993

Inhibitor(s) of natural anti-cardiolipin autoantibodies.

IgG fractions were purified on Sepharose anti-human IgG column from eight sera of healthy donors, having no anti-cardiolipin (aCL) activity as measured by anti-cardiolipin ELISA assay (aCL-ELISA). All the IgG fractions, after elution with 4.9 M MgCl2, reacted with CL. The antigen-binding characteristics of the IgG fractions purified from normal human serum (NHS) were similar to those of IgG fractions purified from sera of four patients with the anti-phospholipid syndrome (APLS). Competition assay confirmed the specificity of the binding of the purified IgG fractions to CL. The same results have been achieved with IgG fractions purified on Sepharose Protein-A column. The binding to CL was completely inhibited by either whole NHS and sera from various animal species, or by beta 2-glycoprotein I (beta 2-GPI). Our results support the notion of the existence of both natural anti-CL antibodies and serum inhibitor(s) in sera of healthy individuals. It is conceivable that in part the pathogenesis of APLS entails defects in the natural inhibitors of aCL antibodies.

Antibodies, Anticardiolipin↗
PubMed1993

The effect of aspirin on recurrent fetal loss in experimental antiphospholipid syndrome.

PURPOSE: To evaluate the effect of aspirin treatment upon fetal loss in mice with experimental antiphospholipid syndrome (APLS). MATERIALS AND METHODS: Experimental APLS was induced in pregnant mice by passive transfer of mouse monoclonal anticardiolipin antibody. The mice were treated with high (100 micrograms/d) or low (10 micrograms/d) dose of aspirin, using vitamin C (100 micrograms/d or 10 micrograms/d) as a control. The mice were assessed for the presence of lupus anticoagulants (prolonged aPTT), thrombocytopenia, degree of fetal resorption rate and mean embryo and placental weights. RESULTS: The mice with APLS had a higher fetal resorption rate (45.7 +/- 12.2% vs 2.5 +/- 0.4%, P < 0.001), reduced placenta mean weight (104 +/- 8 mg vs 169 +/- 7 mg, P < 0.001), prolonged aPTT (94 +/- 14 sec vs 39 +/- 4 sec, P < 0.001), and reduced mean platelet count (597 +/- 186 x 10(3)/mm3 vs 847 +/- 51 x 10(3)/mm3, P < 0.001). The group of mice with APLS, who were treated with low-dose aspirin, had a lower resorption rate (11.1 +/- 9.3% vs 45.7 +/- 12.2%, P < 0.001), a higher placenta mean weight (178 +/- 8 mg vs 104 +/- 8 mg, P < 0.001), a higher mean embryo weight (1042 +/- 134 mg vs 721 +/- 91 mg, P < 0.001), and a lower aPTT (58 +/- 15 sec vs 94 +/- 14 sec, P < 0.001). Mice who were treated with high-dose aspirin also had a lower resorption rate, although not as much as in the low-dose aspirin group (34.2 +/- 12.7% vs 45.7 +/- 12.2%, P < 0.001). CONCLUSION: Aspirin, especially in low dose, has a protective effect against obstetrical complications associated with experimental APLS.

Animals↗
PubMed1993

In vitro effect of anticardiolipin autoantibodies upon total and pulsatile placental hCG secretion during early pregnancy.

BACKGROUND: The anticardiolipin syndrome is characterized among other features by recurrent thromboembolic events, thrombocytopenia, and recurrent fetal loss associated with high IgG titers of anticardiolipin antibodies and/or the presence of lupus anticoagulant. AIMS: The mechanisms for the fetal loss in this syndrome have not yet been clearly elucidated, although several hypothesis based on experimental data have been put forward. We wanted to evaluated the effect in vitro of anticardiolipin antibodies on the secretion of human chorionic gonadotropin. METHODS: Employing our previous experience with placental explants, we studied the effect of several mouse monoclonal and human polyclonal purified anticardiolipin antibodies (ACA), which were shown by us to induce experimental antiphospholipid syndrome (APLS), to affect the pulsatile secretion of beta human choriogonadotropin. RESULTS: The mouse monoclonal ACA antibodies caused an increase in the pulsatility of beta human choriogonadotropin, while human polyclonal ACA derived from patients with ACA had an inhibitory effect. CONCLUSIONS: These studies with placental explants show that ACA may have an additional effect on placental hormone secretion and thus affect the fate of the embryo.

Abortion, Habitual↗
PubMed1993

Pathogenic serum IgG anticardiolipin antibodies and the idiotypic network.

OBJECTIVES: To determine whether active immunisation of mice with pathogenic anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient with the antiphospholipid syndrome, could dysregulate the idiotypic cascade and induce the production of anti-anti-anti-cardiolipin (Ab3) with anticardiolipin activity by the mice with the association of overt antiphospholipid syndrome. METHODS: Anticardiolipin antibodies were purified from the serum of a patient with the antiphospholipid syndrome. The purified anticardiolipin antibodies were used to immunise mice at the footpads and the mice were then followed up for serological and clinical manifestations of the antiphospholipid syndrome. RESULTS: The IgG anticardiolipin antibody was found to be monospecific and to bind cardiolipin with high affinity. Immunisation of naive BALB/c mice with the purified IgG anticardiolipin antibody was followed by production in the mice of sustained high titres of IgG anticardiolipin antibody, associated with a prolonged activated partial thromboplastin time (64.5 (9.7) v 30.1 (1.7) seconds in control mice) and thrombocytopenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/l platelets in controls). The titres of other autoantibodies (for example, antibodies to DNA, histone), though high after the immunisation, decreased rapidly and were almost undetected one month after the boost injection. The mice immunised with the IgG anticardiolipin antibody showed low fecundity (36% of mice became pregnant v 62% in the group immunised with control IgG). The pregnant mice had an increased resorption rate (the equivalent of fetal loss in the human) of 61 (9)% v 5 (4)% in the control group. The mean (SD) embryo and placental weights in mice with the antiphospholipid syndrome were significantly lower than in the mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145 (8) mg respectively. The IgM anticardiolipin antibodies purified from the same patient were found to be polyspecific, binding with low affinity to anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA idiotype 16/6. Mice immunised with the purified IgM anticardiolipin antibodies, though showing reduced fecundity (30%), had only a slightly increased resorption rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non-significant decrease in mean (SD) embryo and placental weights (1134 (188) and 136 (11) mg respectively). CONCLUSIONS: The results confirm the induction of pathogenic anticardiolipin antibodies by immunisation with serum anticardiolipin, dysregulating the idiotypic network, and point to the higher pathogenic potential of serum IgG v IgM anticardiolipin antibodies.

Adult↗
PubMed1993

Interleukin-3 immunoassay in systemic lupus erythematosus patients: preliminary data.

Systemic lupus erythematosus (SLE) may be associated with thrombocytopenia on one hand and lymphoma on the other. Interleukin-3 (IL-3) may contribute to both conditions. IL-3 is a pleotrophic growth factor affecting the proliferation and differentiation of stem cells to committed progenitors of several hematopoietic lineages including megakaryocytes and lymphocytes. The serum level of IL-3 determined by ELISA was found to be higher in a cohort of 16 patients with SLE in comparison to health controls. The IL-3 levels were highest in 2 patients with SLE and lymphoma. Interestingly, low serum levels were detected in SLE patients with thrombocytopenia. Our preliminary results may point to the role of IL-3 in the hematopoietic changes observed in SLE.

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

Pathogenic significance and diagnostic value of lupus autoantibodies.

Systemic lupus erythematosus (SLE) is characterized by a panoply of autoantibodies (more than 50). Some of them are more prevalent (anti-ds DNA > 80%) while others are less frequently detected, but highly specific for SLE (anti-Sm, 20%). In this review we will discuss the clinical significance of anti-RNP, anti-Ro, anti-La and anti-phospholipid antibodies. We will also summarize the clinical and experimental evidence for the pathogenic role attributed to each one of these antibodies.

Antibodies, Antinuclear↗
PubMed1993

Antinuclear antibody profile in UCD line 200 chickens: a model for progressive systemic sclerosis.

The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are fully established, only scarce data are available on the dynamics and clinical significance of autoantibodies in the very early stages of this systemic fibrotic disease. The University of California at Davis line 200 (UCD 200) of chickens spontaneously develop a PSS-like disorder with an acute inflammatory stage around 60 days after hatching, leading to fibrosis with fast progression. In order to address a possible correlation between the occurrence and titer of autoantibodies and the initial disease activity, we have chronologically investigated the presence and titer of autoantibodies directed against several human nuclear antigens in this animal strain. In UCD-200 chickens, we found a progressive increase in autoantibodies to histones, to ssDNA and--to a lesser degree--dsDNA with peaks at the age of 60 and 120 days, to poly(I) and poly(G) with a peak at 120 days and an elevation in anti-cardiolipin antibodies. Total immunoglobulin concentrations, anti-Ro, anti-La and anti-Sm showed no significant differences as compared to negative results in healthy normal controls. Our data reveal parallels in the antinuclear antibody (ANA) spectrum between UCD-200 chickens and human autoimmune collagen diseases, but do not reflect the typical ANA spectrum found in the foudroyant form of diffuse scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.

Animals↗
PubMed1993

Detection of anti-phospholipid and anti-DNA antibodies and their idiotypes in newborns of mothers with anti-phospholipid syndrome and SLE.

The titers, isotypes and idiotypes of antiphospholipid and anti-dsDNA antibodies were determined in seven pairs of mothers with antiphospholipid syndrome (APLS) and their offspring, in 11 pairs of SLE mothers and their matched infants and in seven respective pairs of healthy subjects. In addition, maternal as well as fetal sera were evaluated for the presence of anti-SSA (Ro), anti-SSB (La) and anti-70 kd RNP autoantibodies. In the sera from APLS patients, as well as in the sera from their offspring, the mean antibody titer of IgG aCL was found to be significantly higher then the corresponding value in the control group (P < 0.01). Highly significant increased titers of IgG anti-DNA antibodies were found in the sera of SLE mothers and their matched offspring (P < 0.0008). The prevalence of anti-SSA, anti-SSA, and anti-70Kd RNP antibodies was lower then that of antiphospholipid and anti-dsDNA antibodies. Only one of the respective offspring had increased levels of these antibodies. The quantity of maternal antibodies transferred to the fetus was depended on their concentration in the maternal circulation, as well as on their type and specificity. Follow-up of newborn sera showed a progressive decrease in the antiphospholipid antibody titers during 3 months. After 6 months it was undetected. Our results point to a transplacental transfer of aCL and anti-DNA antibodies, a phenomenon which is not necessarily associated with respective clinical manifestations, in contrast to the classical humoral mediated autoimmune diseases (e.g. myasthenia gravis).

Adult↗
PubMed1993

Autoantibodies to phospholipids and brain extract in patients with the Guillain-Barre syndrome: cross-reactive or pathogenic?

Guillain-Barre syndrome (GBS) is a transient neurological disorder characterized by an inflammatory demyelination of peripheral nerves. Although the pathogenesis of GBS has not been elucidated, there is increasing evidence pointing to an autoimmune etiology. We have studied the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoantigens in other autoimmune conditions. Sixteen Guillain-Barre syndrome (GBS) sera were studied for the presence of autoantibodies to ssDNA, dsDNA, cardiolipin (CL), phosphatidyl-ethanolamine (PE), phosphatidyl-choline (PC), phosphatidyl-serine (PS), and brain extract. Six of the 16 GBS sera had autoantibodies to one or more of the antigens studied. Three of the sera contained autoantibodies to brain extract (p < 0.05), two of the sera had autoantibodies to dsDNA, ssDNA, CL and PE, and one serum had autoantibodies to PC, and PS. As expected a significant proportion of the lupus sera contained autoantibodies to ssDNA and dsDNA, while the frequency of autoantibodies to different phospholipids was significantly high in sera of patients with systemic lupus erythematosus (SLE) and cerebritis. Absorption of GBS sera with cardiolipin, phosphatidyl-choline, or brain extract inhibited the binding of the sera to cardiolipin. Our results demonstrate that some GBS patients produce autoantibodies to various phospholipid and nuclear antigens. However, these autoantibodies are probably produced as a result of the myelin damage rather than cause the demyelination.

Adolescent↗
PubMed1993

Autoimmunity and schizophrenia: an epiphenomenon or an etiology?

During the last 20 years considerable data have accumulated indicating that schizophrenia may have an autoimmune immunology. Patients with schizophrenia may have autoantibodies; in addition, cellular changes may occur that are compatible with autoimmunity, e.g., an increased number of CD5+ cells. If, indeed, schizophrenia does have an autoimmune pathogenesis, we should consider an alternative therapy based on immune system-manipulating drugs in addition to antipsychotic compounds.

Autoantibodies↗