Rheumatoid Arthritis: Ehrenfeld M

Ehrenfeld M, Abu-Shakra M, Buskila D, Shoenfeld Y. · Research Centre for Autoimmune Diseases, Sheba Medical Centre, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Israel. · Blood Cells Mol Dis. · Pubmed #11778659 No free full text.

Abstract: Autoimmune rheumatic diseases and lymphocytic malignancies are related and this association is bidirectional. Lymphomas occur more frequently in the course of autoimmune disease and autoimmune rheumatic manifestations occur in the course of lymphocytic malignancies. An increased incidence of malignant lymphocytic diseases is present in patients with rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and autoimmune thyroid disease. Descriptions of lymphocytic malignancies among other autoimmune rheumatic disease have been published. In some patients, the malignant disease is diagnosed months or years before the appearance of the rheumatic disease.

Ehrenfeld M, Langevitz P, Shoenfeld Y. · No affiliation provided · Harefuah. · Pubmed #10959300 No free full text.

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Herman S, Zurgil N, Langevitz P, Ehrenfeld M, Deutsch M. · The Biophysical Interdisciplinary Schottenstein Center for the Research and the Technology of the Cellome, Bar-Ilan University, Israel. · Clin Exp Rheumatol. · Pubmed #18565255 No free full text.

Abstract: OBJECTIVE: The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement. METHODS: In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients. RESULTS: Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients. CONCLUSION: Our data suggest that, in active RA patients, apoptosis induction by MTX may be primarily due to IL-10 production via modulation of oxidative stress, which may restore the critically important immune balance. These findings may contribute to determining which group of RA patients may better respond to MTX therapy.

Bálint G, Apáthy A, Gaál M, Telekes A, Resetár A, Blazsó G, Falkay G, Szende B, Paksy A, Ehrenfeld M, Shoenfeld Y, Hidvégi M. · Fourth Department of Rheumatology, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary. · Clin Exp Rheumatol. · Pubmed #16870104 No free full text.

Abstract: OBJECTIVE: To investigate the effect of the fermented wheat germ extract (Avemar)in patients with severe rheumatoid arthritis (RA). METHODS: Fifteen female RA (Steinbrocker II-III) patients, who had unsuccessfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used.RESULTS: At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar were observed.CONCLUSION:Supplementation of standard therapies with a continuous administration of Avemar is beneficial for RA patients.

Herman S, Zurgil N, Langevitz P, Ehrenfeld M, Deutsch M. · Physics Department, The Biophysical Interdisciplinary Jerome Schottenstein Center for the Research and the Technology of the Cellome, Bar-Ilan University, Ramat-Gan, Israel. · Immunol Invest. · Pubmed #15495793 No free full text.

Abstract: This cytometric study assesses the effects of methotrexate (MTX) on the expanded CD4+ lymphocyte population in active and nonactive rheumatoid arthritis (RA) patients. In the active patients, MTX was found to reduce the predominant CD4+ CD28+ subpopulation (by 30%), and the minor subpopulation of CD4+ CD28- (by 34%). The incidence of CD25 phenotype was downregulated by 15%. These reductions can be attributed to immunosuppression through apoptosis, which was demonstrated by MTX-induced fluorescein diacetate (FDA) hyperpolarization (an established indicator of early apoptosis). In contrast, in nonactive RA patients, the major CD4+ CD28+ subpopulation of small lymphocytes appeared to be activated by MTX, subsequently transforming into a major hyperblast population, whereas the minor CD4+ CD28- subpopulation was not affected by MTX treatment. The activation by MTX in this group of patients is evidenced by MTX-induced FDA depolarization (an indicator of early activation). Thus, MTX immunosuppressive effect on CD4+ subsets was found in active patients, whereas immunostimulation by MTX was shown in nonactive patients. The found discriminative effect of MTX may suggest a higher effectiveness of low-dose MTX therapy in active RA patients.

Ben-Horin S, Goldstein I, Koltakov A, Langevitz P, Ehrenfeld M, Rosenthal E, Gur H, Bank I. · Chaim Sheba Medical Center, Tel Hashomer, Israel. · J Clin Immunol. · Pubmed #17891451 No free full text.

Abstract: The alpha1beta1 integrin, very late antigen (VLA)-1, characterizes collagen adherent interferon (IFN) gamma producing memory T cells in inflamed synovium. We now report that the mean percentage of VLA-1+ T cells is significantly lower among peripheral blood mononuclear cells of rheumatoid patients responsive to antitumor necrosis factor (TNF) alpha therapy than of those with active disease not receiving therapy. Neutralization of TNFalpha during in vitro polyclonal activation of VLA-1- T cells reduced differentiation to expression of VLA-1 and inhibited secretion of IFNgamma, but did not affect integrin expression on in vivo differentiated VLA-1+ T cells. Moreover, synovial fluids of patients relapsing during and after therapy were enriched in VLA-1+ T cells and lines derived from VLA-1+ T cells in peripheral blood of treated patients retained collagen binding and secreted IFN gamma. Thus, whereas therapy decreases VLA-1+ T cells in rheumatoid arthritis patients, a subset is resistant and contributes to residual and recurring inflammation.

Hassin-Baer S, Levy Y, Langevitz P, Nakar S, Ehrenfeld M. · Department of Neurology, Sackler Faculty of Medicine, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer 52621, Tel-Aviv, Israel. · Clin Rheumatol. · Pubmed #17057945 No free full text.

Abstract: The nervous system may be involved in up to 30% of patients with Sjogren's syndrome (SS). We describe three patients with Sjogren's syndrome and a concomitant parkinsonian syndrome. Elevated titers of anti-beta2-glycoprotein I IgG were found in the serum of all three patients. This autoantibody is strongly associated with anticardiolipin (aCL) antibodies, antiphospholipid syndrome (APS), and thromboembolic phenomena, but its role in the pathogenesis of the parkinsonian disorder in SS is unclear. These patients may present a subtype of SS patients in which the presence of aCL antibodies is associated with central nervous system involvement predominantly in the basal ganglia.

Herman S, Zurgil N, Langevitz P, Ehrenfeld M, Deutsch M. · The Biophysical Interdisciplinary Schottenstein Center for the Research and the Technology of the Cellome, Physics Department, Bar-Ilan University, Ramat-Gan 52900, Israel. · Cell Struct Funct. · Pubmed #12808231 links to  free full text

Abstract: The objectives of this study were to test the in vitro response of healthy non-activated, activated, and rheumatoid arthritis (RA) lymphocytes to methotrexate (MTX), and design an in vitro model for predicting the efficiency of MTX treatment for RA patients. Considering the RA profile of clonal-expanded CD4(+) T cells, phytohemagglutinin-activated mononuclear cells taken from healthy donors were incubated with different concentrations of MTX. The MTX-immunosuppressive effect was tested by fluorescence intensity measurements, including PI assay and annexin V assay. For simple detection, we used the Individual Cell Scanner (IC-S), which enables the measurement of early events in individual cells. Healthy mononuclear cells (MNC), and MNC derived from RA patients, were tested by the IC-S while utilizing fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) as an established marker of activation or suppression. In healthy activated MNC, we found that MTX, through its early incubation period, interferes with the activation signal obtained by PHA and exerts an apoptotic signal, which is noted by increases in the FP. Comparing our model to six long-standing RA patients and five newly-diagnosed patients revealed significant differences in the FP measurements, including fluorescence depolarization as an early established measurement of lymphocyte activation, and hyperpolarization as a measurement of an early immunosuppressive effect. We conclude that MTX, an effective therapy for RA patients, could easily be tested by fluorescence polarization measurements of FDA before (or during) clinical use in order to predict its efficiency on a specific RA patient. Moreover, the FP measurements can be used for the diagnosis, and making timing and dosage decisions.