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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 181 records · Page 10Linked to original sources
PubMed2000

The prediction of coronary atherosclerosis employing artificial neural networks.

BACKGROUND: Atherosclerosis is a complex histopathologic process that is analogous to chronic inflammatory conditions. Several factors have been shown to correlate with the extent of atherosclerosis. Whereas hypertension, obesity, hyperlipidemia, diabetes, smoking, and family history are all well documented, recent literature points to additional associated factors. Thus, antibodies to oxidized low-density lipoprotein (oxLDL), cytomegalovirus (CMV), Chlamydia pneumonia, Helicobacter pylori, as well as homocysteine and C-reactive protein (CRP) levels have all been implicated as independent markers of accelerated atherosclerosis. HYPOTHESIS: In the current study we attempted to formulate a system by which to predict the extent of coronary atherosclerosis as assessed by angiographic vessel occlusion. METHODS: The 81 patients were categorized as having single-, double-, triple-, or no vessel involvement. The clinical data concerning the "classic" risk factors were obtained from clinical records, and sera were drawn from the patients for determination of the various parameters that are thought to be associated with atherosclerosis. RESULTS: Using four artificial neural networks, we have found the most effective parameters predictive of coronary vessel involvement were (in decreasing order of importance) antibodies to oxLDL, to cardiolipin, to CMV, to Chlamydia pneumonia, and to beta 2-glycoprotein I (beta 2GPI). Although important in the prediction of vessel occlusion, hyperlipidemia, hypertension, CRP levels, and diabetes were less accurate. CONCLUSION: The results of the current study, if reproduced in a larger population, may establish an integrated system based on the creation of artificial neural networks by which to predict the extent of atherosclerosis in a given subject fairly and noninvasively.

Aged↗
PubMed2000

Vaccination and autoimmunity-'vaccinosis': a dangerous liaison?

The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this issue (although the temporal relationship (i.e. always 2-3 months following immunization) is impressive).

Animals↗
PubMed2000

Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis.

Heat shock proteins are a family of approximately 25 highly conserved proteins upregulated in response to various forms of stress. They play an active role in the development autoimmune diseases in animals, and have been incriminated in human autoimmune diseases (i.e. rheumatoid arthritis, multiple sclerosis). It has been previously shown, that an induced immune response against Heat shock protein 65 (HSP-65) results in atherosclerotic lesions in normocholesterolemic rabbits. We have supported these findings showing that C57BL/6 mice immunized with HSP-65 and fed a high-fat diet develop enhanced fatty streaks. To create a model that will eliminate the need for exogenous supplementation of a high-fat diet, we have immunized LDL receptor deficient (LDL-RD) mice with HSP-65 or with heat-killed Mycobacterium tuberculosis (Mt). Seven groups of LDL-RD mice (n=10), were immunized subcutaneously with different concentrations of HSP-65, Mt or bovine serum albumin (BSA). All mice were fed a normal chow-diet for 3 months. The mice immunized with the higher doses of Mt developed significantly larger fatty streaks when compared with their BSA immunized littermates. The size of the lesions in the aortic sinus were: 31,562+/-5,994 microm(2)in the 10 microg Mt and 52,777+/-5,245 microm(2)in the 100 microg Mt vs. 11, 500+/-3,750 microm(2)in the BSA group (P<0.05). In the HSP-65-immunized mice, only the group injected with the highest dose (5 microg, twice) developed significantly larger fatty streaks when compared with the BSA-immunized group (28,611+/-4,716 microm(2)vs. 11,500+/-3,750 microm(2)respectively, (P<0.05). The HSP-65-but not the Mt- or BSA-immunized mice developed high titers of anti HSP-65 antibodies, beginning 10 days after the immunization, which persisted until they were killed. Immunohistochemical staining showed CD3-positive lymphocytes in the aortic sinus of mice immunized with Mt or HSP-65, but not in the control group. Thus, we established a mouse model of HSP-65 immune mediated atherosclerosis devoid of high fat diet supplementation. This model will enable us to further study the role of the immune system in atherosclerosis, via HSP-65 and raise novel immunomodulatory therapeutic modalities.

Animals↗
PubMed2000

Heat shock protein 60/65, beta 2-glycoprotein I and oxidized LDL as players in murine atherosclerosis.

We have made consecutive studies to prove that autoimmune factors can influence the progression of atherosclerosis in inbred and transgenic mice. C57BL/6 as well as LDL-receptor deficient mice were immunized with heat shock protein 65. LDL-RD and apolipoprotein E knockout (apoE KO) mice were immunized with human B-glycoprotein I. ApoE KO mice were immunized with oxidized LDL. In all immunized mice, a sustained humoral response to the provided antigen was elicited evident by high titers of antibodies by ELISA. A primary cellular immune response was also shown by thymidine incorporation studies employing the antigens in vitro. Immunization with hsp-65 and with beta 2-GPI served to enhance the progression atherosclerosis and led to an increase in the infiltration of CD3 in the subendothelial regions of the early plaques. Transfer of hsp-65 and beta 2-GPI reactive lymphocytes to syngenic mice led to enhancement of fatty streak formation. However, immunization with homologous oxLDL in apoE KO mice led to attenuation of lesion progression concomitant with the production of anti-oxLDL antibodies. Thus, autoimmune factors appear to influence early artherosclerosis progression in mice. If proven in humans these antigen specific responses may be harnessed for selective immunomodulation of the atherosclerotic plaque.

Animals↗
PubMed2000

Linseed oil suppresses the anti-beta-2-glycoprotein-I in experimental antiphospholipid syndrome.

The immunomodulatory potential of a diet enriched with n-3 polyunsaturated fatty acids was analysed in naïve mice with experimental antiphospholipid syndrome (APS) induced by active immunization with H-3, a human anti-beta-2-glycoprotein-I (anti-betaGPI) monoclonal antibody (mAb). Fetal loss and other clinical manifestations of APS were prevented in the group of APS mice upon exposure to the enriched n-3 diet compared to the control group. The titers of anti-betaGPI were significantly lower (in O.D. at 405 nm, 1.387+/-0.232 in comparison to non-treated mice 0.637+/-0. 111, P< 0.05). The reduced titer of anti-betaGPI antibodies in the sera of the treated mice was associated with a reduced number of anti-betaGPI forming cells in cultured splenocytes (84+/-14, antibody-forming cells (AFC)/10(5)cells in comparison to 37+/-4 AFC/10(5)cells (P< 0.02).In addition to the suppression of the humoral response in mice with experimental APS fed with linseed oil, we also observed an inhibitory effect on the cellular response. The T-cell response to anti-betaGPI was lower in comparison to mice immunized with H-3 anti-betaGPI mAB, which were kept on a normal diet. These results indicate that polyunsaturated fatty acids may improve clinical and laboratory parameters of APS. The beneficial effects of diets enriched with n-3 should be further examined as a potential mode of therapy for patients with APS.

Animals↗
PubMed2000

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

Adult↗
PubMed2000

Skin score decrease in systemic sclerosis patients treated with intravenous immunoglobulin--a preliminary report.

The aim of the study was to determine for the first time the response of systemic sclerosis (SSc) patients to treatment with intravenous immunoglobulin (IVIg). Three patients with progressive and rapidly deteriorating disease (mainly affecting the skin) were planned to receive six monthly courses of high-dose IVIg (2 g/kg). All had a thorough physical examination, clinical evaluation by the modified Rodnan total skin thickness score, and measurement of the titres of PM-Scl antibodies before and after the treatment, and before and after each treatment course. Two of the three patients received six IVIg courses as planned and no adverse effects or disease progression occurred during the therapy. The third patient received three courses, after which he developed renal failure and later died of sepsis. All three patients had a large decrease in their skin score after the treatment compared to that before the treatment. No modification of PM-Scl antibody titres was noted in any patient. Intravenous immunoglobulin (IVIg) may have a role in the treatment of SSc patients with rapidly deteriorating skin disease. The specific indications, as well as the safety of this treatment, should be further researched.

Adult↗
PubMed2000

Intravenous immunoglobulin treatment of lupus nephritis.

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.

Adolescent↗
PubMed2000

Serum autoantibodies in patients with primary sclerosing cholangitis.

BACKGROUND/AIM: Primary sclerosing cholangitis is a chronic cholestatic syndrome with a presumed autoimmune basis frequently associated with inflammatory bowel disease. The aim of this study was to determine the profile and significance of serum autoantibodies in patients with primary sclerosing cholangitis. METHODS: Serum samples taken from 73 untreated patients (32 female and 41 male, median age 45 years) with well-defined primary sclerosing cholangitis, and from 75 healthy age- and sex-matched controls were assayed for 20 different autoantibodies. RESULTS: Of 73 patients, 71 (97%) were positive for at least 1 autoantibody; whereas 59/73 patients (81%) were positive for > or =3 antibodies. Patients with primary sclerosing cholangitis had a significantly greater rate of positivity than controls for antinuclear, anticardiolipin, antineutrophil cytoplasmic, and antithyroperoxidase antibodies as well as rheumatoid factor. The rate of positivity and serum levels of any of these 20 autoantibodies were not significantly different between patients with primary sclerosing cholangitis and inflammatory bowel disease and those without inflammatory bowel disease. Anticardiolipins were the single group of antibodies that had a significant correlation with the Mayo risk score (r=0.49, p<0.001) and histologic stage of disease (r=0.30, p<0.01). CONCLUSIONS: Primary sclerosing cholangitis is associated with a high proportion of non-organ specific autoantibodies. Anticardiolipin antibodies appear to be related to the severity of primary sclerosing cholangitis and may be a useful prognostic marker.

Adult↗
PubMed2000

Treatment of hematologic disorders other than immune thrombocytopenic purpura with intravenous immunoglobulin (IVIg) - report of seven cases and review of the literature.

Background: Intravenous immunoglobulin (IVIg) is a standard therapeutic modality for a few autoimmune diseases, such as immune thrombocytopenic purpura. However, in other hematologic autoimmune conditions its role is still controversial. Methods: Seven patients with either autoimmune hemolytic anemia, Evans' syndrome, aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, or acquired factor VIII inhibitors were treated with a single course of high-dose (2 g/kg) IVIg. Results: A good response was observed in all seven patients, except the one with thrombotic thrombocytopenic purpura, and there were no adverse effects related to IVIg use. The literature reports on IVIg therapy in these conditions and the mechanisms of action of IVIg in autoimmune diseases are discussed. Conclusions: IVIg might be a useful agent in the treatment of several hematologic disorders other than immune thrombocytopenic purpura. Future aims of clinical research in this respect would be to identify the patient subgroups that might benefit more from IVIg in these conditions.

Journal Article↗
PubMed2000

Novel approaches to therapy for systemic lupus erythematosus.

Current therapies for systemic lupus erythematosus (SLE) are targeted at immunosuppression and at reducing inflammation. The current therapies are broad-spectrum and include steroids and cytotoxic agents that are counterbalanced by toxicity and side effects of the medications. Methotrexate can be utilized to reduce steroid requirements in mild to moderate SLE. Manipulation of the hormonal axis includes DHEA and bromocriptine. Mycophenolate mofetil is an immunosuppressive agent that is being investigated for SLE renal disease. Autologous stem cell transplantation or high-dose cyclophosphamide may be an option for severe refractory SLE. The aim of the future is to target therapies by altering specific known mechanisms of inflammation and autoimmunity. Although the inciting antigen is still unknown in SLE, it may be possible to alter the regulation of the immune response by targeted molecular therapy. Methods to do so would include manipulation of idiotypes, manipulation of second signal stimulation of the immune response, manipulation of cytokines, and the induction of tolerance by administration of blocking peptides. IVIg is an immunomodulator that has been successful in the treatment of SLE. Targeted molecular therapy is undergoing phase I trials with monoclonal anti-CD40L, a signaling inhibitor. Anti-CTLA4Ig, another signaling blocker, is presently being investigated for psoriasis, but may be a potential therapy for SLE. Finally, therapies may include the administration of peptides to induce tolerance.

Journal Article↗
PubMed2000

Is cancer an autoimmune process dependent on anti-apoptotic autoantibodies?

Dysregulated apoptosis is a potentially important mechanism in the pathogenesis of cancer. Autoantibodies, which inhibit apoptosis, have recently been identified in patients with malignant diseases. We suggest that such inhibitory autoantibodies participate in tumorigenesis. These views may provide a basis for the increased incidence of cancer in patients with autoimmune diseases and have novel therapeutic implications for cancer.

Apoptosis↗
PubMed2000

Anti-cardiolipin antibodies in fetal blood and amniotic fluid derived from patients with the anti-phospholipid syndrome.

The aim of this study was to investigate whether, in patients with antiphospholipid syndrome, anticardiolipin antibodies pass from mother to offspring sera and amniotic fluid. Eleven patients with antiphospholipid syndrome (study group) and 11 healthy controls, matched by maternal and gestational age (control group) were prospectively examined for the presence of anticardiolipin antibodies in the cord blood during labour, and amniotic fluid during vaginal or Caesarean delivery. Three neonates (27.3%) in the study group had anticardiolipin antibodies in the cord blood, while none had them in the control group. Anticardiolipin antibodies were detected in the amniotic fluid in six (54.5%) of the study group pregnancies, compared with none in the control group. No adverse neonatal outcome was noted except for significantly lower (P < 0.0006) mean birth weight in the study group. Anticardiolipin antibodies can pass the placenta and be detected in fetal cord blood and amniotic fluid. This finding might be used in the future for the assessment of pregnancies with antiphospholipid syndrome.

Amniotic Fluid↗
PubMed2000

Intravenous immunoglobulin therapy of antiphospholipid syndrome.

OBJECTIVE: To review the role of intravenous immunoglobulin (IVIg) in antiphospholipid syndrome (APS). METHODS: A literature search was carried out for the immunopathogenesis of APS, laboratory evidence for the beneficial effect of IVIg in APS, and the clinical use of IVIg in APS. RESULTS: There is both laboratory and clinical evidence for the beneficial role of IVIg in APS. IVIg succeeded in in vitro inhibition of anticardiolipin antibodies and lupus anticoagulant, and in the amelioration of experimental APS. Although there are few case reports about IVIg therapy in the haematological manifestations of APS, most of the reports focus on the use of IVIg in the obstetric complications of APS. Hence, in several patient series the use of IVIg either solely or in combination with aspirin/heparin resulted in successful pregnancy outcome in the vast majority of APS patients with recurrent abortions. In addition, IVIg was also beneficial in antiphospholipid antibody-positive patients undergoing in vitro fertilization. CONCLUSION: APS, an autoimmune disease whose main features are vascular thrombosis and pregnancy morbidity, is a good candidate for immunotherapy with IVIg that contains anti-idiotypes directed towards patients' pathogenic antiphospholipid antibodies. Future research should determine when to use anticoagulation, IVIg or both in the treatment of APS.

Adult↗
PubMed2000

Antiphospholipid syndrome: insights from animal models.

Animal models of the relatively new antiphospholipid syndrome (APS) enabled researchers to understand disease pathogenesis and to test novel experimental therapeutic modalities. Animal models of APS include spontaneous genetic models and experimental induced models. The latter test more reliably the pathogenicity of antiphospholipid antibodies because the syndrome is induced in normal mice rather than being secondary to a preexisting autoimmune disease. Reports about animal models of APS in the recent year provide new insights into the pathogenesis of antiphospholipid antibodies and beta2-glycoprotein-I in reproductive failure, neurologic manifestations, thrombosis, and atherosclerosis. In addition, novel therapies that were successful in experimental APS included anti-idiotypes, oral tolerance, and specific peptides that bind to beta2-glycoprotein-I. Animal models provide the first step in development of novel therapies for patients with APS.

Animals↗
PubMed2000

Ciprofloxacin affects pregnancy loss in CBA/JxDBA/2J mice possibly via elevation of interleukin-3 and granulocyte macrophage-colony stimulating factor production.

PROBLEM: The mechanisms mediating pregnancy loss are far from being understood, but it is believed that modulation of the maternal immune system, that is known to support pregnancy, might serve as a means for the treatment of habitual abortions. Thus, we examined the effect of the anti bacterial agent ciprofloxacin, which was shown to affect maternal immunoreactivity, on pregnancy loss in the resorption-prone CBA/JxDBA/2J mouse combination as well as associated changes in Interleukin (IL)-3 and Granulocyte macrophage-colony stimulating factor (GM-CSF) production. METHOD OF STUDY: CBA/J females mated to DBA/2J males were treated with ciprofloxacin for 5 consecutive days. On day 15 of pregnancy, the number of resorbed embryos was recorded and IL-3 mRNA expression as well as IL-3 and GM-CSF protein production by splenocytes were assayed by northern blotting and ELISA, respectively. RESULTS: Ciprofloxacin treatment resulted in a significant reduction in the resorption rate as compared to the effect of the control antibiotic ceftazidime or PBS only, while not affecting the number of implantation sites/mouse. Also, splenocytes from ciprofloxacin-treated CBA/J mice exhibited an increased level of IL-3 mRNA transcripts as well as an elevation in IL-3 and GM-CSF protein production. CONCLUSIONS: Our data demonstrate the ability of ciprofloxacin to reduce pregnancy loss in the CBA/JxDBA/2J mouse model, possibly via elevation of IL-3 and GM-CSF production.

Abortion, Veterinary↗
PubMed2000

The idiotypic network in antinuclear-antibody-associated diseases.

Antinuclear antibodies (ANA) entail a large group of autoantibodies (Abs) that bind certain nuclear antigens. The ANA test is a useful screening test for many autoimmune diseases and the presence of a specific binding pattern directs secondary testing for specific Abs associated with the suspected disease. Idiotypes (Ids) are the antigenic constitution of the variable region of an Ab, and they are recognized by anti-Ids Abs. The Id network is composed of interacting Abs in which the Id determinants of each Ab are complemented by those of another. It has a role in both physiologic and pathologic conditions. In this communication, we review the induction of autoimmune diseases via Id manipulation, the Ids of some ANA-associated Abs (DNA, SS-A, SS- B, Sm Abs), the pathogenic role of Abs carrying Ids, and the clinical implications of the Id network in autoimmunity.

Animals↗