Search PubMed⌕ Search

Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 919 records · Page 51Linked to original sources
PubMedDate not supplied

A malignancy work-up in patients with cancer-associated (paraneoplastic) autoimmune diseases: pemphigus and myasthenic syndromes as cases in point (review).

Although some autoimmune diseases are known to be associated with a higher incidence of cancers, they are not usually considered as paraneoplastic diseases, but rather as autoimmune diseases that may be neoplasia-associated, since currently it is not known whether the tumor leads to their development, or alternatively another underlying condition turns the patients prone to both cancer and autoimmunity. We review the association of cancer with pemphigus, paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and discuss the importance of looking for an occult malignancy in a patient with a newly-diagnosed autoimmune disease that is known to be associated with cancer.

Humans↗
PubMedDate not supplied

[Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity].

BACKGROUND: There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA) are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. OBJECTIVES: To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. METHODS: Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score < or =3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. RESULTS: Patients had higher intima-media thickness than controls of all the sites evaluated at carotid artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. CONCLUSIONS: Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Valvular deposition of antiphospholipid antibodies in the antiphospholipid syndrome: a clue to the origin of the disease.

In this report we present an unusual case of a 45-year-old female patient with systemic lupus erythematosus (SLE) who was hospitalized for mitral valve replacement. In her childhood she presented with mitral stenosis and chorea on which grounds a preliminary diagnosis of rheumatic fever was established. After a quiescent period lasting two decades her disease erupted with mitral stenosis, thromboembolic phenomena, and nephritis. Due to severe malfunctioning of her mitral valve, the patient eventually underwent mitral valve replacement. The antibodies involved in the pathogenesis of our patient's valvular disease were studied by immunohistochemical analysis, applying rabbit polyclonal anti-human IgG and IgM anti-human C3c and anti-idiotypes to a mouse monoclonal naturally occurring polyspecific human monoclonal anti-cardiolipin antibody termed S2.9, and to the 16/6 Id which defines a common Id on anti-DNA antibodies in patients with SLE. Immunoperoxidase staining using an anti-idiotype mAb to anti-cardiolipin antibodies demonstrated the deposition of these anti-bodies in the subendothelial layer of the valve. We believe that anti-phospholipid syndrome (APS) with SLE was the initial and primary disease in this patient. These findings clearly indicate that APS must be considered in the differential diagnosis of rheumatic fever, particularly in young female patients who present with mitral stenosis and chorea.

Adolescent↗
PubMedDate not supplied

Cytokines in experimental autoimmune vasculitis: evidence for a Th2 type response.

OBJECTIVE: To investigate the pathogenic role of cytokines in the development of experimental autoimmune vasculitis. METHODS: BALB/c mice were immunized with human IgG-ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse IgG-ANCA and other autoantibodies were determined. The mice lungs and kidneys were examined for the development of vasculitis. Levels of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, interferon gamma (IFN gamma) and TNF alpha were determined by ELISA two weeks after immunization of the mice. RESULTS: Mice immunized with human IgG-ANCA developed anti-human IgG-ANCA (= Ab2) and anti-anti-human IgG-ANCA (mouse IgG-ANCA = Ab3), while the controls did not develop these antibodies. The mice that were immunized with human IgG-ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. Levels of IL-4, IL-6 and TNF alpha but not IL-1 beta, IL-2 and IFN gamma were significantly elevated in the mice 2 weeks after immunization with IgG-ANCA. CONCLUSION: Our results suggest a pathogenic role for IL-4, IL-6 and TNF alpha in the initiation phase of autoimmune vasculitis. This suggests that a Th2 type immune response is responsible for the initiation of experimental autoimmune lung vasculitis, similar to Wegener's granulomatosis in humans.

Animals↗
PubMedDate not supplied

Use of intravenous immunoglobulin in livedo vasculitis.

We describe a 36-year-old woman with livedo vasculitis (atrophie blanche) lasting for 15 years. After the failure of numerous therapeutic modalities the patient was treated with intravenous immunoglobulin. Significant resolution of the cutaneous lesions was seen with a concomitant alleviation of pain. To the best of our knowledge this is the first patient with livedo vasculitis described in the medical literature ever to be treated with IVIG and to achieve a successful outcome.

Adult↗
PubMedDate not supplied

Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/beta 2-glycoprotein-I (beta 2GPI) complex and induces APS.

OBJECTIVE: As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through different target epitopes located on the beta-2-glycoprotein-I (beta 2GPI) molecule, the aim of this study is to describe an additional target epitope for anti-cardiolipin binding. METHODS: The binding characteristics of affinity purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy associated with clinically overt APS were studied; inhibition studies were also carried out. These antibodies were used for the active induction of experimental APS. RESULTS: The affinity purified anti-cardiolipin antibodies were found to bind a target epitope created by the complex of cardiolipin/beta 2GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/beta 2GPI), as confirmed by direct binding and competition assays. Immunization of naive mice with this unique affinity purified anti-cardiolipin antibody resulted in the induction of experimental APS (thrombocytopenia, prolonged coagulation timed and fetal resorptions). The anti-cardiolipin/beta 2GPI injected mice developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction. CONCLUSION: APS is a unique syndrome that is characterized by a diversity of pathogenic anti-phospholipid antibodies which may explain the diversity of clinical manifestations reported in patients.

Aged↗
PubMedDate not supplied

Isotretinoin-induced adult onset Still's disease.

We describe a 21-year old man who was diagnosed as having adult onset Still's disease (AOSD) in association with isotretinoin treatment for acne conglobata. The patient was febrile, with a macular salmon pink rash, arthritis, hepatosplenomegaly, and axial lymphadenopathy. Laboratory results showed leukocytosis, mild liver dysfunction and negative rheumatoid factor and antinuclear antibodies. Isotretinoin, an orally active derivative of vitamin A, has been associated with various rheumatologic conditions such as arthralgia, myalgia, vasculitis and arthritis. The etiology of rheumatic disorders associated with retinoids is still obscure; however, it is presumed that immunomodulation by several mechanisms (such as an alteration of the cytokine balance) is probably ascribable to this interesting association.

Adult↗
PubMedDate not supplied

Induction of anti-RA33 hnRNP autoantibodies and transient spread to U1-A snRNP complex of spliceosome by idiotypic manipulation with anti-RA33 antibody preparation in mice.

OBJECTIVE: Anti-RA33 antibodies occur in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD) and target the A2/B1 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex 4 which forms part of the spliceosome. The aim of the present study was to evaluate the immune response and pathological features induced in mice immunized with anti-RA33 antibodies or patient-derived recombinant single-chain variable fragments (scFv) of anti-RA33 antibodies. METHODS: In the first set of the experiment, two strains of mice (C57BL/6J and BALB/c) were immunized with IgG preparations obtained from two patients with RA and one normal donor. One of the patients had high titer anti-RA33 antibodies; the other one showed weak borderline reactivity. In the second set of the experiment three groups of C57BL/6J mice were immunized, respectively, with affinity-purified (AP) anti-RA33 antibodies, scFv of anti-RA33 antibodies and normal human IgG. The immunological response induced in immunized mice was studied by immunoblotting and line immunoassay (LIA). The presence of arthritis, serositis or myositis was assessed six-months following initial immunization. RESULTS: While anti-RA33 antibodies developed in only two of the mice immunized with different human IgG fractions, anti-RA33 antibodies were clearly detected in 7 sera of 13 mice immunized with AP anti-RA33 antibodies three months after the boost immunization and, moreover, also in 2 sera of 13 mice immunized with scFv of anti-RA33 antibodies. In contrast, mice immunized with normal human IgG did not develop anti-RA33 antibodies. Interestingly, transient autoantibody production against another nuclear autoantigen, U1 snRNP, was observed in 3 C57BL/6J mice immunized with scFv and in 1 mouse immunized with AP autoantibodies. However, these immunological responses were not associated with pathological findings. CONCLUSIONS: Active immunization of naive mice with AP anti-RA33 antibodies and scFv of anti-RA33 antibodies resulted on the one hand in the production of murine anti-RA33 antibodies and led, on the other hand, to transient "autoantibody spread" to snRNP component of the spliceosome and other nuclear autoantigens. This "autoantibody spread" probably reflected disregulation of the idiotypic anti-idiotypic cascade.

Animals↗
PubMedDate not supplied

Transverse myelitis associated with chronic hepatitis C.

An infectious etiology is one of the postulated mechanisms for autoimmune diseases. An emergence of autoimmune phenomena associated with hepatitis C virus (HCV) infection has been reported. Transverse myelitis is an inflammatory disease of the spinal vasculature attributed to viral infections and to autoimmune diseases including systemic lupus erythematosus and the antiphospholipid syndrome. A 34-year-old male was admitted for the rapid onset of numbness of the lower extremities and urinary retention. His past history included hepatitis C infection. The neurological examination and MRI of the thoracic spine confirmed the diagnosis of transverse myelitis. Abnormal laboratory results were hyperglobulinemia, abnormal liver function tests, and positive ANF, anti-dsDNA antibodies, and p and c-ANCA. The patient was treated with high dose prednisone, then tapered to a low dose, but regained only partial neurological function after 15 months of prednisone therapy. Persistent neurological deficits and elevated ANF and ANCA were present at a follow-up of 30 months. We describe the first reported case of a patient with chronic HCV who developed transverse myelitis.

Adult↗
PubMedDate not supplied

Successful treatment of psychosis secondary to SLE with high dose intravenous immunoglobulin.

A 23-year-old woman with SLE was admitted because of severe psychosis manifested by depression, delusions and the inability to perform minimal daily activities. The patient refused treatment with steroids, but was later convinced to try treatment with intravenous immunoglobulin (IVIG). Following treatment with IVIG a marked improvement was noted in her mental status and she was discharged. During a follow-up period of 18 months she resumed normal life; she does not receive any drugs currently and no psychiatric abnormalities have been noted. It is suggested that IVIG may be considered in the treatment of lupus cerebritis, especially when serious complications develop and other treatment modalities are ineffective.

Adult↗
PubMedDate not supplied

The beta-2-glycoprotein I and antiphospholipid antibodies.

Beta 2-GPI is a single chain, 50 kd glycoprotein made up of 326 amino-acids, present in human plasma at concentrations of about 200 micrograms/ml. It has been shown to represent the "serum cofactor" important in determining the binding of aCL to phospholipids both in fluid and in solid phase assays. Its cofactor activity is demonstrable for aPL antibodies from patients with autoimmune but not with infectious diseases. It is immunogenic in heterospecific models, and immunization with beta 2-GPI seems to be able to induce the production not only of anti-beta 2-GPI but also of aPL antibodies. Most probably its binding to CL changes the configuration of phospholipids to a more immunogenic one. The various characteristics of beta 2-GPI are summarized in Table I. beta 2-GPI has been recognized as a natural anticoagulant protein, but its possible role in the pathogenesis of the APLS remains to be determined.

Antiphospholipid Syndrome↗
PubMedDate not supplied

Guillain-Barré syndrome following hepatitis B vaccination.

A 52-year-old woman developed Guillain-Barré syndrome 10 weeks after immunization with recombinant hepatitis B vaccine. Common infectious causes of GBS were ruled out. The temporal relationship between GBS and hepatitis B virus (HBV) vaccination was suggestive of a vaccine-induced cause. The possible mechanisms of this very, rare complication are discussed.

Female↗
PubMedDate not supplied

Livedo reticularis is a marker for predicting multi-system thrombosis in antiphospholipid syndrome.

OBJECTIVE: Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome). METHODS: In a cohort of APS patients we investigated the possible association of LR with various clinical aspects of APS such as pregnancy morbidity, central nervous system (CNS) and cardiac manifestations. RESULTS: Livedo reticularis was found in 50/308 (16%) of APS patients, and there was a significant association with cerebrovascular accidents (CVA), migraines and epilepsy (p = 0.01, 0.002, and 0.02 respectively). A similar association was also detected between LR, and the presence of cardiac valve thickening and vegetations (p = 0.001). No association with venous thrombosis, recurrent fetal loss, IUGR or toxemia was found. CONCLUSION: Livedo reticularis is a frequent cutaneous manifestation in patients with APS. Its high association with cardiac and CNS thrombosis may suggest that LR-APS patients compose a subset at higher risk for thrombosis, and thus may require a closer follow-up and a more aggressive anticoagulation.

Adult↗
PubMedDate not supplied

New insights into the autoantibody-mediated mechanisms of autoimmune bullous diseases and urticaria.

The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.

Autoantibodies↗
PubMedDate not supplied

New aspects in the treatment of immunomediated diseases.

The following constitutes a summary of lectures delivered during the session "New aspects in the treatment of immunomediated diseases" which was held during the 25th Annual Scientific Meeting of the European Society for Clinical Investigation in Pisa, Italy on 6th April 1991. The aim of this session was to present and discuss some of the novel therapeutic modalities currently being employed either in experimental models or in phase I clinical studies.

Adjuvants, Immunologic↗