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Biomedical subjects

Yaniv Sherer

Publications and source records attributed to Yaniv Sherer.

At least 19 recordsLinked to original sources
PubMed2006

Matrix metalloproteinase-9 and autoimmune diseases.

Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.

Autoimmune Diseases↗
PubMed2006

Pathogenic role and clinical relevance of antineutrophil cytoplasmic antibodies in vasculitides.

Within the last year, a growing body of evidence for a distinct role of antineutrophil cytoplasmic antibodies (ANCA) in the pathogenesis of ANCA-associated vasculitides (AAV) has developed. An experimental model of myeloperoxidase (MPO)-ANCA-associated vasculitis provided direct and convincing in vivo evidence that MPO-ANCA are primary pathogenic factors in small-vessel vasculitis by augmenting of leukocyte-vessel wall interaction and leukocyte-mediated vascular injury. Determination of bacterial lipopolysaccharide (LPS) effects on disease severity in a mouse model of anti-MPO-induced glomerulonephritis showed that ANCA and other proinflammatory stimuli of infectious origin acted in synergism in the development of destructive inflammation.

Animals↗
PubMed2006

Mechanisms of disease: atherosclerosis in autoimmune diseases.

Atherosclerosis is a pathologic process affecting blood vessels, which leads to the development of cardiovascular disease. The immune system is involved in atherogenesis and in the pathogenesis of atherosclerosis. Several autoimmune rheumatic conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterized by enhanced atherosclerosis and consequently higher cardiovascular morbidity and mortality rates. Enhanced atherosclerosis, in these diseases, can manifest as overt cardiovascular diseases, but could be detected at an earlier stage by identification of abnormal endothelial function and arterial intima-media thickening. Both classical and nonclassical risk factors are presumed to contribute to atherosclerosis progression in rheumatic diseases. As atherosclerosis can be considered to be an immune-mediated process, several experimental strategies exist for its immunomodulation, including induction of immune tolerance. In this article, we briefly review the contribution of autoimmune elements, such as autoreactive lymphocytes and autoantibodies to atherosclerosis and discuss the nature of atherosclerosis in autoimmune rheumatic diseases.

Animals↗
PubMed2005

The infectious etiology of the antiphospholipid syndrome: links between infection and autoimmunity.

Like many other autoimmune diseases, the antiphospholipid syndrome (APS) is considered as of a multifactorial etiology, mainly genetic susceptibility coinciding with environmental triggers, of which infectious agents are considered most prominent. Different clinical and experimental studies of the beta2 glycoprotein I (beta 2 GPI) molecule, one of the target autoantigens in APS, have linked infection to the development of APS. Using a peptide phage library, it has been shown that target epitopes of beta 2 GPI share similarities with common infectious pathogens. Also, circulating anti-beta 2 GPI antibodies have been identified in the sera of patients with different infectious conditions, and have been associated with various clinical APS manifestations. Molecular mimicry as a key mechanism linking infection and APS has been demonstrated in experimental models. In these studies, APS was induced by immunization of mice to various microbial pathogens. Anti-beta 2 GPI titers were found to be especially high following immunization with Haemophilus influenzae, Neisseria gonorrheae or tetanus toxoid. These findings contribute greatly to the understanding of APS pathogenesis, as well as create new directions for therapy modalities, namely specific peptide toleragens and antimicrobial treatment.

Animals↗
PubMed2005

Intravenous immunoglobulin for immunomodulation of systemic lupus erythematosus.

Intravenous immunoglobulin (IVIg) is used for replacement therapy in immunodeficiency states and for immunomodulation of various autoimmune diseases. Several case reports and series support a beneficial role of IVIg in systemic lupus erythematosus (SLE), both as salvage immunotherapy and in control of disease activity in general and amelioration of classical disease manifestations. Further, lupus nephritis can also be treated usually successfully with IVIg. A few questions remain unanswered as to the appropriate therapeutic dosage and the clinical manifestations that can be best treated with IVIg.

Glomerulonephritis↗
PubMed2005

Inflammation and accelerated atherosclerosis: basic mechanisms.

This article summarizes knowledge of the pathogenic mechanisms in autoimmune rheumatic diseases as risk factors for accelerated atherosclerosis. The studies described support a role for immunologic-inflammatory mechanisms in the pathogenesis of atherosclerosis. This immunologic-inflammatory state is evident in many autoimmune diseases, but also in the general population lacking an overt autoimmune disease. The ability to immunomodulate atherosclerosis (currently only experimental) should lead to future research into the mechanisms and treatment of atherosclerosis, the leading cause of death in the Western world.

Arteriosclerosis↗
PubMed2005

Early atherosclerosis in rheumatoid arthritis: effects of smoking on thickness of the carotid artery intima media.

This study was designed to compare intima media thickness (IMT) of the carotid arteries among rheumatoid arthritis (RA) patients and controls and to determine whether disease-associated characteristics, smoking, and other classic risk factors for atherosclerosis are associated with IMT values. IMT was measured in the carotid arteries of 101 RA patients and 75 control subjects. The IMT was evaluated in the common carotid (CC), carotid bifurcation (BI), and internal carotid (IC). Eight IMT values were calculated including four mean and four maximal values of CC, BI, IC, and carotid artery (C). The following data were obtained for every patient: age, sex, body mass index (BMI), presence of erosions, extra-articular manifestations, rheumatoid factor, medications, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, daily number of cigarettes, number of smoking years, family history of cardiovascular diseases (CVD), and erythrocyte sedimentation rate (ESR) levels. RA patients had significantly higher mean-BI IMT than controls (1.02 mm vs. 0.89 mm; P < 0.01), higher incidence of increased mean-BI IMT and max-BI IMT, but lower incidence of increased max-IC IMT than controls. Factors significantly associated with IMT in the controls were age, BMI, and hypertension, whereas factors significantly associated with IMT in RA patients were age and smoking status. Mean carotid IMT was associated with all characteristics related to smoking in RA patients. Current smokers had higher mean carotid IMT and internal carotid artery IMT than former smokers. RA is associated with higher carotid artery bifurcation IMT. The profile of factors associated with IMT values is different between RA patients and controls. Smoking is an important factor augmenting early atherosclerosis in RA patients.

Adult↗
PubMed2005

Prevalence of antiphospholipid and antioxidized low-density lipoprotein antibodies in rheumatoid arthritis.

Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.

Antibodies, Anticardiolipin↗
PubMed2005

Response of vasculitic peripheral neuropathy to intravenous immunoglobulin.

Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it responds to corticosteroids therapy, but in certain cases it may resist corticosteroid or immunosuppressive treatment, or both. The objective of this study is to present case reports of patients who exhibited various inflammatory diseases, accompanied with vasculitic peripheral neuropathies, for which intravenous immunoglobulin (IVIg) was used for treatment. The study included 10 patients with the following: Sjögren's syndrome (1), systemic lupus erythematosus (2), vaccination-induced vasculitis (1), Churg-Strauss vasculitis (1), mixed cryoglobulinemia (2), polyarteritis nodosa (1), sarcoidosis (1), and scleroderma (1). All developed vasculitic peripheral neuropathy and were treated with 1-13 cycles of high-dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. Results showed that in all but two patients (mixed cryoglobulinemia associated with hepatitis C and sarcoidosis), neuropathy improved or completely resolved after IVIg treatment. In conclusion, IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment in patients for whom conventional treatment is contraindicated, or for patients in whom conventional treatment has failed.

Child↗
PubMed2005

Intravenous immunoglobulin: adverse effects and safe administration.

Intravenous immunoglobulin (IVIg) is administered for various indications and generally considered a safe therapy. Most of the adverse effects (AEs) associated with IVIg administration are mild and transient. The immediate AEs include headache, flushing, malaise, chest tightness, fever, chills, myalgia, fatigue, dyspnea, back pain, nausea, vomiting, diarrhea, blood pressure changes, tachycardia, and anaphylactic reactions, especially in IgA-deficient patients. Late AEs are rare and include acute renal failure, thromboembolic events, aseptic meningitis, neutropenia, and autoimmune hemolytic anemia, skin reactions, and rare events of arthritis. Pseudohyponatremia following IVIg is important to be recognized. Renal failure, usually oliguric and transient, occurs mostly on using sucrose-containing products owing to osmotic injury. Among high-risk patients who have a previous renal disease, dehydration, diabetes mellitus, advanced age, hypertension, hyperviscosity, or are treated by other nephrotoxic medications, administration of a non-sucrose-containing IVIg product after accomplishing hydration, in a low concentration and a slow infusion rate while supervising urine output and kidney function, is recommended. Thromboembolic complications occur because of hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic diseases, being bedridden, diabetes mellitus, hypertension, dyslipidemia, or those receiving high-dose IVIg in a rapid infusion rate. Immediate AEs can be treated by the slowing or temporary discontinuation of the infusion and symptomatic therapy with analgesics, nonsteroidal anti-inflammatory drugs, antihistamines, and glucocorticoids in more severe reactions. Slow infusion rate of low concentration of IVIg products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis.

Acute Kidney Injury↗
PubMed2005

Laparoscopic inguinal hernioplasty in aviators.

Repair of inguinal hernias may be performed using either open surgery or laparoscopic techniques. Following surgery, a 6-wk waiting period is generally recommended before a pilot returns to active duty, including flight in high-performance aircraft. A shorter waiting period would be operationally useful and may be possible following either a trans-abdominal preperitoneal (TAPP) laparoscopic technique or a totally extra-peritoneal (TEP) approach. In this manuscript we present the cases of four aviators who underwent inguinal hernia repair via the TEP approach and were returned to the cockpit 21 d later with no evident complications. Although this sample is small, it emphasizes the potential benefit of the TEP approach in aviators.

Adult↗
PubMed2005

[Accelerated atherosclerosis in rheumatoid arthritis].

Cardiovascular manifestations are frequent in rheumatoid arthritis (RA) and significantly contribute to morbidity and mortality in this disorder. Premature atherosclerosis is responsible for these complications, as supported by autopsy studies. Moreover, a high prevalence of sub-clinical atherosclerosis--evaluated by imaging and instrumental parameters--has been reported. Traditional risk factors cannot completely account for accelerated atherosclerosis in RA. The presence of RA by itself and the immunosuppressive therapy (especially corticosteroids) represent non-traditional risk factors for premature atherosclerosis. Additional factors playing a synergistic role in the atherosclerotic process are systemic chronic inflammation frequently associated with RA and both humoral and cellular specific autoimmune responses. Herein we review and discuss atherosclerosis in rheumatoid arthritis, with special emphasis on clinical presentations, pathogenesis and therapy.

Arteriosclerosis↗
PubMed2005

[Dermatological manifestations in the antiphospholipid syndrome].

Antiphospholipid syndrome is regarded as a systemic disease. A total of 41% of the patients are presented with one form of the diverse skin findings at diagnosis. Due to the high prevalence of skin affliction it was recently suggested to include this syndrome in the diagnostic criteria of APS. The importance of these findings also entails the fact that in 25% of the patients the skin manifestations precede thromboembolic phenomena. The findings entail livedo reticularis, anetoderma, skin necrosis and others. This article discusses their prevalence and their relationships to other clinical manifestations in APS and how to approach them therapeutically.

Antiphospholipid Syndrome↗
PubMed2005

Low levels of heat shock proteins-60 and -65 autoantibodies in Sjögren's syndrome.

BACKGROUND: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65 and human HSP60 have been established in a number of human autoimmune diseases. OBJECTIVE: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjögren's syndrome as compared to normal subjects. METHODS: Thirty-seven patients with SS were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens. RESULTS: The levels of both anti-HSP60 and -HSP65 were lower in patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 +/- 55.1 ng/ml in controls versus 112.3 +/- 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among the SS patients: 111.6 +/- 33.4 U/ml versus 96.1 +/- 8.9 U/ml (P= 0.01). CONCLUSIONS: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies in larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

Autoantibodies↗
PubMed2004

Aortic valve calcification in hypertensive patients: prevalence, risk factors and association with transvalvular flow velocity.

BACKGROUND: The important role of the "nonobstructive" aortic valve calcification (AVC) in cardiovascular morbidity and mortality has recently been emphasized. The present work had two goals: (1) to analyze the prevalence and factors determining the extent of AVC in hypertensive patients; (2) to investigate a possible association between the extent of AVC and flow velocity across the aortic valve. METHODS: This was a prospective study performed in a university hospital. The sample included 263 consecutive patients (139 men and 124 women), mean age 65+/-6, who underwent echo-Doppler. The upper quartile of peak flow velocity across the aortic valve (>130 mm/s in our population) was defined as augmented flow velocity. RESULTS: There were 31 (12%) patients in the advanced AVC group and 122 (46%) without any calcified deposits (the no AVC group). The remaining 110 (42%), who did not meet criteria for advanced AVC, comprised the trivial AVC group. Peak flow velocity was significantly higher in patients with advanced vs. trivial AVC and no AVC groups: 135+/-45, 116+/-23 and 113+/-23 cm/s, respectively; p=0.0002. Prevalence of augmented transvalvular aortic flow was significantly higher (p=0.01) among patients with advanced AVC (41.9%) vs. trivial (20.9%) and no AVC (20.5%). Multivariate analyses identified age as the only independent variable associated with advanced AVC [OR 1.6 (CI 1.2-2.3), 5 years increment]. Advanced AVC and female gender were identified as independent variables for augmented transvalvular aortic flow with OR 2.9 (CI 1.3-6.4) and 2.5 (CI 1.4-4.6), respectively. CONCLUSIONS: Prevalence of AVC among hypertensive patients is high and clearly age-related. Female gender and advanced (but not trivial) AVC are associated with augmented aortic transvalvular peak flow. Our results stress the role of protruding calcium deposits in augmentation of rest flow velocity across the aortic valve regardless of visible restriction of leaflet opening.

Age Factors↗
PubMed2004

Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients.

OBJECTIVE: Description of the various autoantibodies that can be detected in patients with systemic lupus erythematosus (SLE). METHODS: A literature review, using the terms "autoantibody" and "systemic lupus erythematosus", was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity, or other clinical associations. RESULTS: One hundred sixteen autoantibodies were described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 116 autoantibodies. CONCLUSIONS: SLE is the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of polyclonal B cell activation, impaired apoptotic pathways, or the outcome of idiotypic network dysregulation.

Autoantibodies↗
PubMed2004

Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.

BACKGROUND: No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD. DESIGN: Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events. METHODS: The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl). RESULTS: Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29). CONCLUSIONS: Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.

Aged↗