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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 505 records · Page 28Linked to original sources
PubMed1994

Isotypic distribution of anti-pyruvate dehydrogenase antibodies in patients with primary biliary cirrhosis and their family members.

IgG subclasses of anti-pyruvate dehydrogenase (PDH) antibodies were determined in 72 patients with primary biliary cirrhosis. All isotypes were detected, but IgG3, IgG1, and IgG2 predominated independently or in association. An average of 33.3 +/- 19.1% of the anti-PDH IgG was IgG1 (mean optical density, 0.863 +/- 0.783, vs 0.053 +/- 0.038 in the normal controls), 25.0 +/- 17.8 IgG2 (0.652 +/- 0.656 vs 0.062 +/- 0.030), 39.5 +/- 23.4% IgG3 (1.140 +/- 0.917 vs 0.010 +/- 0.023), and 2.4 +/- 7.4% IgG4 (0.060 +/- 0.182 vs 0.012 +/- 0.007). Anti-PDH IgG were restricted to IgG1 in the family members of patients (0.180 +/- 0.403).

Adolescent↗
PubMed1994

Antimitochondrial (pyruvate dehydrogenase) antibodies in leprosy.

Sera from 69 patients with leprosy but without liver involvement were assayed for the presence of mitochondrial pyruvate dehydrogenase (PDH)-specific autoantibodies by enzyme-linked immunoabsorbent assay (ELISA), immunoblotting using PDH as an antigen and by enzymatic inhibition test. Twenty-seven of the leprosy serum samples (39.1%) were found to react with PDH by ELISA. However, unlike sera from primary biliary cirrhosis (PBC) patients, none of these were able to inhibit the PDH enzymatic activity. By immunoblotting, it was found that only 2 of the 27 positive sera recognized the 74-kD protein of the PDH complex, which is recognized by sera of most PBC patients. The antimitochondrial antibodies in lepra most probably recognize different epitopes than those in PBC. These findings may indicate that anti-PDH autoantibodies in patients with leprosy may arise by polyclonal B cell stimulation and may represent natural anti-PDH autoantibodies.

Autoantibodies↗
PubMed1994

Sjogren's syndrome in Israel: primary versus secondary disease.

Sixty Israeli patients, 30 with primary Sjögren's syndrome (SS) and 30 with rheumatoid arthritis (RA) and secondary SS, were evaluated. The Schirmer-1 test and a positive labial salivary gland biopsy were found to be the most helpful tools in assessing the diagnosis of SS. Extraglandular features such as Raynaud's phenomenon, lymphadenopathy and CNS involvement as well as parotid gland enlargement (p < 0.05) were more common in primary SS. Antinuclear antibodies, especially anti-Ro (SSA) and anti-La (SSB) were also more common in primary SS (p < 0.05). Our results are in accord with those of many European centers, despite the different genetic background.

Adult↗
PubMed1994

Autoimmune multiorgan involvement in elderly men is it SLE?

Systemic lupus erythematosus (SLE) in males and especially in the elderly is infrequent. We describe two male patients over 65 years old, who presented with anaemia, cytopenia, nephritis, and serositis, suggesting that they suffered from an autoimmune disease. Following an interval of 6 and 9 years respectively, the diagnosis of SLE was made. In both patients, hypothyroidism, and eye involvement (uveitis and iridocyclitis) were present indicating autoimmune activity or even a new autoimmune syndrome. One patient was treated with corticosteroids and azathioprine upon which he developed many side effects from the steroid therapy. The other patient received treatment with intravenous immunoglobulin (IVIG), and at a follow-up period of 18 months, the patient's condition remained stable. We suggest that in the constellation of clinically multiple organ involvement in the elderly male, the diagnosis of SLE should be considered. IVIG may be a successful alternative therapy in this subset of patients.

Aged↗
PubMed1994

The coexistence of systemic lupus erythematosus with other autoimmune diseases: the kaleidoscope of autoimmunity.

Patients with systemic lupus erythematosis (SLE) often manifest features of other autoimmune diseases. In this review, we provide a detailed compendium of features of SLE that overlap with other conditions. This compendium is important because a critical feature in our understanding of autoimmunity has been the clustering of coexisting/different autoimmune diseases both within an affected patient and within a pedigree. Indeed, autoimmune disorders share a variety of similar clinical and serological defects. For example, all autoimmune disorders are associated with the elaboration of autoantibodies and/or the production of self-reactive mononuclear cell populations; many have high levels of immune complexes and defects in cell-mediated immunity. Several diseases share similar genetic backgrounds, as reflected by study of loci within the major histocompatibility complex. In part the coassociation is due to common genetic tendencies with different environmental precipitating agents (trigger mechanisms). It is likely that many factors can modulate the immune system to autoimmunity in the presence of an appropriate genetic background, eg, drugs, viral infections, UV irradiation, and toxins, ie, toxic oil syndrome and L-tryptophan-induced eosinophilic myalgia. The coexistence of SLE with other autoimmune diseases is an excellent venue to understand these events, and we believe that the presence of other autoimmune diseases in patients with SLE can be called the kaleidoscope of autoimmunity.

Autoimmune Diseases↗
PubMed1994

Idiotypic induction of autoimmunity: a new aspect of the idiotypic network.

Three different experimental models of autoimmune diseases were induced in naive mice after idiotypic immunization. 1) systemic lupus erythematosus (SLE) after injection of anti-DNA antibodies carrying the pathogenic Id-16/6; 2) anti-phospholipid syndrome (APLS) after immunization with anti-cardiolipin antibodies (having the pathogenic H-3 and MIV-7 Ids); and 3) Wegener's granulomatosis (WG) induced with anti-neutrophile cytoplasmic antibodies (ANCA). In all three experiments the mice developed the respective anti-Id antibodies (Ab2), and, after a follow-up period of 4-8 months anti-anti-Id (Ab3) were generated by the immunized mice. The latter antibodies (Ab3) had the binding characteristics of the respective autoantibodies (Ab1) used in the first immunization. The appearance of auto-antibodies in the sera of the mice was associated with emergence of all the typical clinical and laboratory findings seen in patients with SLE, APLS, and WG, respectively. We suggest that in some autoimmune diseases, especially in those in which the presumed autoantigen is not immunogenic (e.g., DNA, cardiolipin), the disease may follow a common infection: The antibodies against the infecting agent may carry a pathogenic idiotype of a specific autoantibody. In a subject prone to autoimmunity (genetic, hormonal, immunologic factors), the pathogenic idiotype will progress in dysregulating the immune system to evolve into a clinical overt autoimmune disease.

Animals↗
PubMed1994

Suppression of experimental systemic lupus erythematosus (SLE) with specific anti-idiotypic antibody-saporin conjugate.

The importance of the idiotypic network is represented in experimental SLE induced by active immunization of naive mice with an anti-DNA idiotype (Ab1) emulsified in adjuvant. The mice after 4 months of incubation generate Ab3 having anti-DNA activity. In addition, the mice develop other serological markers for SLE associated with clinical and histopathological manifestations characteristic of the disease. To confirm further the etiological role of the idiotype in this experimental model, the mice were treated with specific anti-idiotypic antibodies (anti-Id) which were also conjugated to a toxin-saporin (Immunotoxin (IT)). Pretreatment of hybridoma cell line producing the anti-anti-Id (anti-DNA = (Ab3)) for 48 h with the anti-Id MoAb (Ab2) reduced the production of anti-DNA by 58%, while pretreatment with the IT resulted in 86% decrease in anti-DNA secretion (saporin alone had only 12% effect). The anti-Id MoAb had no effect on the production of immunoglobulin by an unrelated cell line. In vivo treatment of mice with experimental SLE led to a significant decrease in titres of serum autoantibodies, with diminished clinical manifestations. The results were more remarkable when the IT was employed. These suppressive effects were specific, since an anti-Id treatment of experimental anti-phospholipid syndrome was of no avail. The anti-Id effect was mediated via a reduction in specific anti-DNA antibody-forming cells, and lasted only while anti-Id injections were given. Discontinuation of the anti-Id injection was followed by a rise in titres of anti-DNA antibodies. No immunological escape of new anti-DNA Ids was noted. Our results point to the importance of pathogenic idiotypes in SLE and to the specific potential of implementing anti-idiotypic therapy, enhanced by the conjugation of the anti-Id to an immunotoxin, in particular one with low spontaneous toxicity.

Animals↗
PubMed1994

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy.

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from patients with monoclonal gammopathies (MG). ACA were purified from the sera of patients with MG. One of the IgG-ACA was found to be monospecific with high affinity for cardiolipin, and to carry a pathogenic ACA Id (1.10). Active immunization of naive BALB/c mice with the purified IgG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin time (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468,000 +/- 224,000/mm3 versus 994,000 +/- 92,000/mm3 in controls; P < 0.001). The titres of other autoantibodies (e.g. anti-DNA, anti-histones), although being high after immunization, decreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundity (36% of mice became pregnant versus 62% observed in the group immunized with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/- 4% in the control group). The mean (+/- s.d.) embryo and placental weights in mice with anti-phospholipid syndrome (APLS) were significantly lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respectively; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.

Adult↗
PubMed1994

Antigens and antibodies in malignant melanoma.

Antigens, antibodies and immune complexes seem to play a major role in the course of malignant melanoma, in detection of the disease progression, in treatment planning and monitoring. Of particular interest are cell and matrix adhesion molecules, growth factors and cytokines, proteases, gangliosides and major histocompatibility complex class I and II molecules. Antigens expressed on melanoma cells, but not on mature melanocytes, may be used as markers for the degree of the differentiation of the melanoma cells. The more the melanoma cells are dedifferentiated, the smaller is the antigenic similarity to normal melanocytes. Also, different antigens may be identified in various stages of the disease and may be used as tumor markers for disease recurrence or progression. Certain melanoma-associated antigens (MAA) such as epidermal growth factor receptor and adhesium molecules can be modulated by cytokines. Early melanoma evokes an antigen-derived T cell response, which becomes attenuated with the progression of the disease. A variety of cell adhesion molecules present on melanoma cell surfaces may play a role in regulation of cellular cytotoxicity. Free antimelanoma antibodies are usually not detectable in the sera of patients with melanoma, possibly due to their binding to shed antigens and formation of immune complexes or to tissue antigens. When bound to normal melanocytes, they cause the appearance of associated hypopigmentation. The identification of melanoma surface antigens led to generation of monoclonal antimelanoma antibodies (MAb) by laboratories. Strategies utilizing MAb based on immunologic approaches have been developed. MAb to tumor-associated antigens of melanoma cells may be used for therapeutic purposes in man. Sera of patients with vitiligo were capable of causing regression of melanoma metastases in mice due to the presence of a high titer of naturally occurring antimelanoma antibodies. Immunization of melanoma patients with vaccines containing treated melanoma cells or specific melanoma antigens or anti-idiotypic antibodies resulted in an increasing titer of antimelanoma antibodies and regression of the tumor to some extent. The appearance of hypopigmentation in patients with melanoma serves as proof for the activity of antimelanoma antibodies, although its association with the prognosis is still not clear. The thorough investigation in the field of MAA and related antibodies is aimed at improving specific antimelanoma immunotherapy, such as antigenic targeting or enhancement of production of autoantibodies, as well as better understanding of the process of metastasis and the melanoma-immune system interaction.

Animals↗
PubMed1994

Anti-idiotypes and their application under autoimmune, neoplastic, and infectious conditions.

Idiotypes and anti-idiotypes are becoming widely used in various experimental applications in multiple fields of research. Administration of anti-idiotypes has been attempted in order to manipulate immune reactions affecting autoimmune, neoplastic, and infectious processes. Immunization with anti-idiotypes and idiotypes may change the autoantibody expression in autoimmune diseases. In certain experimental models administration of anti-idiotypes and idiotypes may even propagate the induction of autoimmune-like disorders. Internal image bearing anti-idiotypes may provide an effective tool in the combat of neoplastic and infectious diseases. Such anti-idiotypes may resemble the structure of neoplastic cell antigen or mimic the composition of a contagious viral antigen. This review will deal in detail with the various aspects of idiotype and anti-idiotype immunomanipulation.

AIDS Vaccines↗
PubMed1994

Anti-endothelial cell antibodies: a need for standardization.

Twenty years have passed since the original description of the anti-endothelial cell antibodies (AECA). It is widely acknowledged that the presence of circulating autoantibodies against endothelial cells surface antigens, found in a number of patients with connective tissue disease and vasculitis, is one of the driving mechanisms for the observed vascular injury and might be an important factor in initiating the pathogenesis of vascular abnormalities. AECA data regarding the prevalence, technical problems, presence with other autoantibodies, antigen distribution and immune endothelial cell injury associated with these autoantibodies, requires standardization for determining the precise pathophysiologic and immunologic role of anti-endothelial cell antibodies.

Autoantibodies↗
PubMed1994

Role of IL-3 in the antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is characterized by recurrent thromboembolic phenomena, thrombocytopenia and fetal loss. We describe various methods of induction of experimental APLS. These models were employed to study a variety of therapeutic agents including low dose aspirin, low molecular weight heparin, IVIG and thromboxane receptor antagonist. Because interleukin-3 (IL-3) is a multilineage cytokine affecting also megakaryocytes, is regarded as a 'good' cytokine in various stages of pregnancy and as low levels of IL-3 were recorded in APLS, it was logical to employ IL-3 as a therapy for APLS. Indeed, this treatment completely abrogated all the manifestations of experimental APLS. Furthermore, it was found that low dose aspirin most probably affect positively APLS via inducing an increased production of IL-3 by monocytes.

Animals↗
PubMed1994

Effect of long-acting thromboxane receptor antagonist (BMS 180,291) on experimental antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent thromboembolic phenomena, recurrent fetal loss and thrombocytopenia associated with high titers of IgG anticardiolipin antibodies and/or lupus anticoagulant. There is an increased platelet aggregation in these patients and thus aspirin was found to be effective in abrogating some of the clinical findings. The purpose of this study was to employ the experimentally induced APS in mice infused with anticardiolipin antibodies, to study the effect of a thromboxane receptor antagonist (BMS, 180, 291) on the various overt manifestations of APS. Experimental APS was induced in pregnant female mice by iv infusion of a pathogenic anticardiolipin antibody (CAM). The mice were then treated daily with 300 micrograms/mouse of BMS. The study group and the untreated group were killed on day 17 of pregnancy. Live and absorbed fetuses and the mean weight of the placentae, fetuses and platelet counts were recorded. BMS treated mice had a significant reduction in fetal resorption rate from 45% to 19.8% and an increase in mean placental and embryo weights (182 vs 104, 1043 vs 721 mg, respectively). In parallel, an increase in platelet count (from 597,100 to 1075,000 platelets/mm3) and decrease in activated thromboplastin time (95 to 44s) was seen. It seems that thromboxane receptor antagonist may be effective in abrogating the diverse manifestations seen in APLS. Increased platelet aggregation may be one of the pathogenetic mechanisms in APS.

Animals↗
PubMed1994

Anticardiolipin antibodies in infections are heterogenous in their dependency on beta 2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy.

We studied the effect of beta 2-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine beta 2-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without beta 2-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of beta 2-GPI on the leprosy and APS sera binding to CL was confirmed using purified human beta 2-GPI. Enhanced binding was seen if beta 2-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against beta 2-GPI were found by ELISA. Leprosy anti-beta 2-GPI antibodies appear to be a separate antibody population recognizing only beta 2-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their beta 2-GPI requirement for binding to CL.

Antibodies, Anticardiolipin↗
PubMed1994

Anti-nuclear antibodies associated with schistosomiasis and anti-schistosomal antibodies associated with SLE.

Various autoantibodies to nuclear antigens were detected by ELISA in pooled sera of 15 ICR mice 9 weeks after infection with schistosoma. The binding of this serum with acute infection to cercarial extract was inhibited by prior incubation of the sera with DNA, polynucleotides and cercarial extract. Sera from 9 BALB/c mice with experimentally induced lupus, reacted with cercarial extract. No binding was noted with normal mouse sera (NMS). Similarly, sera of SLE patients (N = 113) reacted with the parasite extracts in a higher incidence (14.2%) compared to NHS (3.7%) (P < 0.05). Immunoblot analysis showed common features to SLE sera reacting with two antigenic "groups". The first are antigens that also were recognized by sera of mice infected with schistosomiasis (60, 85, and 94 kDa cercarial proteins). The second group entailed proteins that bound with SLE sera only (10-18 kDa, 29 kDa and 52 kDa). It can be concluded that antinuclear autoantibodies can be found in sera of acute infected mice with schistosomiasis, while SLE sera may react with 3 schistosomal extracts in a higher incidence than NHS (P < 0.05). These results suggest an autoimmune response in schistosomiasis. It is possible that a parasite infection (as bilharzia) may be one of the "trigger" mechanisms for SLE in a subject with the suitable immunogenetic and hormonal background.

Animals↗