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  1. Article ; Online: The role of B cell metabolism in autoimmune diseases.

    Mubariki, Raeda / Vadasz, Zahava

    Autoimmunity reviews

    2022  Volume 21, Issue 7, Page(s) 103116

    Abstract: B cells are major players in immune responses being the source of protective antibodies and antigen presenting cells. When self-tolerance fails, auto reactive B cells produce autoantibodies and pro-inflammatory cytokines leading to the development of ... ...

    Abstract B cells are major players in immune responses being the source of protective antibodies and antigen presenting cells. When self-tolerance fails, auto reactive B cells produce autoantibodies and pro-inflammatory cytokines leading to the development of autoimmune diseases. Many recent studies have assessed importance of metabolic pathways in B cells, demonstrating their role in controlling autoimmunity and maintaining immune homeostasis. Alterations in B cell functions in autoimmune diseases are closely associated with abnormal metabolic shifts, allowing auto reactive B cells to escape tolerogenic checkpoints. Understanding the metabolic changes in B cells, opens up new possibilities for targeting metabolic pathways and manipulating metabolic avenues as a therapeutic strategy for the treatment of autoimmune diseases.
    MeSH term(s) Autoantibodies ; Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; Humans ; Immune Tolerance
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2022-05-17
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2144145-5
    ISSN 1873-0183 ; 1568-9972
    ISSN (online) 1873-0183
    ISSN 1568-9972
    DOI 10.1016/j.autrev.2022.103116
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    Zs.A 5913: Show issues Location:
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  2. Article: Rheumatology and Autoimmunity in The Israel Medical Association Journal (IMAJ): 2017.

    Vadasz, Zahava

    The Israel Medical Association journal : IMAJ

    2017  Volume 19, Issue 12, Page(s) 781–783

    MeSH term(s) Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/psychology ; Arthritis, Rheumatoid/therapy ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; Autoimmunity ; Biological Therapy/methods ; Biological Therapy/trends ; Biomarkers ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Quality of Life ; Rheumatology/trends
    Chemical Substances Biomarkers ; Immunoglobulins, Intravenous
    Language English
    Publishing date 2017-12-08
    Publishing country Israel
    Document type Editorial
    ZDB-ID 2008291-5
    ISSN 1565-1088 ; 0021-2180
    ISSN 1565-1088 ; 0021-2180
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  3. Article ; Online: Predictive features associated with chronic spontaneous urticaria recurrence.

    Toubi, Elias / Vadasz, Zahava

    The Journal of dermatology

    2021  Volume 48, Issue 11, Page(s) 1786–1788

    Abstract: When chronic spontaneous urticaria (CSU) is resolved, patients are often apprehensive about the likelihood of recurrence, and want to know if we can predict this using clinical or laboratory markers. This question is crucial because CSU is frequently ... ...

    Abstract When chronic spontaneous urticaria (CSU) is resolved, patients are often apprehensive about the likelihood of recurrence, and want to know if we can predict this using clinical or laboratory markers. This question is crucial because CSU is frequently accompanied by a high incidence of stressful comorbidities, and the fear of experiencing this again can be devastating to the patient. This study was designed with the aim of focusing on the prevalence and characteristics of the recurrence of CSU. We used our CSU patient registry that includes data on 180 patients who are followed periodically. In 23 (13%) patients, CSU was resolved during the first year. In 47 (26%) patients, CSU lasted more than 5 years. The recurrence of CSU was recorded in 21% of our patients after having experienced a full remission anywhere between 1 to 10 years (mean ± 2.9 years). While investigating predictive clinical or laboratory markers, we noticed that bronchial asthma existed in 10/25 (40%) of patients in whom CSU recurred as compared with 45/180 (25%) in the general CSU population (p = 0.049). In addition, increased levels of total immunoglobulin (Ig)E were found in 10/25 (40%) of the recurrence group as compared with 34/150 (23%) of the general CSU group (p = 0.04). Anti-thyroid peroxidase antibodies were also found in 11/25 (44%) of the recurrence group as compared with 32/160 (20%) of the general group (p = 0.003). The prevalence of CSU recurrence after a full remission is significantly higher among patients with existing bronchial asthma, increased levels of total IgE, and autoimmunity. Further studies are required in order to substantiate this important issue.
    MeSH term(s) Autoimmunity ; Chronic Disease ; Chronic Urticaria ; Comorbidity ; Humans ; Urticaria/diagnosis ; Urticaria/epidemiology
    Language English
    Publishing date 2021-09-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 800103-0
    ISSN 1346-8138 ; 0385-2407
    ISSN (online) 1346-8138
    ISSN 0385-2407
    DOI 10.1111/1346-8138.16119
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  4. Article: The Emerging Role of IL-17 in the Immune-Pathogenesis of Chronic Spontaneous Urticaria.

    Toubi, Elias / Vadasz, Zahava

    ImmunoTargets and therapy

    2020  Volume 9, Page(s) 217–223

    Abstract: Chronic spontaneous urticaria (CSU) is considered to be an autoimmune disorder (type I and type II) in 50% of all cases. However, autoreactive T cells and their proximity with activated mast cells in the skin of CSU patients are believed to be the ... ...

    Abstract Chronic spontaneous urticaria (CSU) is considered to be an autoimmune disorder (type I and type II) in 50% of all cases. However, autoreactive T cells and their proximity with activated mast cells in the skin of CSU patients are believed to be the primary event in mast cell degranulation. The finding of anti-FcɛRIα on mast cells or IgE autoantibodies against thyroid antigens should be considered to be a consequence of the auto-reactive T cells' recognition of the above-mentioned antigens. Our recent finding of increased Th17 and IL-17 expression in both CD4+ T cells and mast cells in the skin of severe CSU patients is supportive for the major role that T cells perform in the pathogenesis of CSU. Supporting this are numerous previous reports in which increased serum IL-17 was found to be in association with CSU disease severity. The beneficial effect of anti-IL-17A (secukinumab) in CSU patients in whom high dose anti-histamines, recurrent course of steroids and omalizumab fail to achieve a reasonable response should be investigated as a new therapeutic strategy in future studies with a large cohort of patients.
    Language English
    Publishing date 2020-10-22
    Publishing country New Zealand
    Document type Journal Article ; Review
    ISSN 2253-1556
    ISSN 2253-1556
    DOI 10.2147/ITT.S266410
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  5. Article: Truncated-semaphorin3A is a potential regulatory molecule to restore immune homeostasis in immune-mediated diseases.

    Eiza, Nasren / Kessler, Ofra / Sabag, Adi / Neufeld, Gera / Jones, E Yvonne / Vadasz, Zahava

    Frontiers in pharmacology

    2023  Volume 13, Page(s) 1085892

    Abstract: Regulatory molecules have recently been recognized for their beneficial effects in the treatment of immune-mediated diseases, rather than using cytotoxic immune-suppressing drugs, which are associated with many unwanted side effects. Semaphorin3A (sema3A) ...

    Abstract Regulatory molecules have recently been recognized for their beneficial effects in the treatment of immune-mediated diseases, rather than using cytotoxic immune-suppressing drugs, which are associated with many unwanted side effects. Semaphorin3A (sema3A), a unique regulatory master of the immune system, was shown to be decreased in the serum of systemic lupus erythematosus (SLE) patients, in association with disease severity. Later, we were able to show its extremely beneficial effect in treating lupus nephritis in the NZB/W mice model. The mechanisms by which sema3A maintains its regulatory effect is by binding the regulatory receptor CD72 on B cells, thereby reducing the threshold of BCR signaling on B cells and reducing the production of pro-inflammatory cytokines. The aim of this study was to generate a stable sema3A molecule, easy to produce with a higher binding capacity to CD72 receptor rather than to Neuropilin-1 (NRP-1) receptor, which is expressed in many cell types. Using the crystallographic structure of parental sema3A, we synthesized a new secreted (shorter) sema3A derivative, which we called truncated sema3A (T-sema3A). The new molecule lacked the NRP-1 binding domain (the C-terminal site) and has an artificial dimerization site at position 257 (serine residue was exchanged with a cysteine residue). To facilitate the purification of this molecule we added Histidine epitope tag in frame upstream to a stop codon. This construct was transfected using a viral vector to 293HEK cells to generate cells stably expressing T-sema3A. T-sema3A is shown to be with a higher binding ability to CD72 than to NRP-1 as demonstrated by a homemade ELISA. In addition, T-sema3A was shown to be a regulatory agent which can induce the expression of IL-10 and TGF-β and reduce the secretion of pro-inflammatory cytokines such as IL-6, IFN-γ, and IL-17A from human T and B-lymphocytes. Keeping this in mind, T-sema3A is highly effective in maintaining immune homeostasis, therefore, becoming a potential agent in restoring the regulatory status of the immune system in immune-mediated diseases.
    Language English
    Publishing date 2023-01-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.1085892
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  6. Article ; Online: Think autoimmunity, breath autoimmunity, and learn autoimmunity.

    Toubi, Elias / Vadasz, Zahava

    Clinical rheumatology

    2019  Volume 38, Issue 5, Page(s) 1227–1230

    MeSH term(s) Arthritis, Rheumatoid/therapy ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/etiology ; Autoimmune Diseases/immunology ; Autoimmunity ; Humans
    Language English
    Publishing date 2019-04-12
    Publishing country Germany
    Document type Editorial
    ZDB-ID 604755-5
    ISSN 1434-9949 ; 0770-3198
    ISSN (online) 1434-9949
    ISSN 0770-3198
    DOI 10.1007/s10067-019-04540-2
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    Zs.A 1740: Show issues Location:
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  7. Article ; Online: Semaphorin3A is a promising therapeutic tool for bronchial asthma.

    Toubi, Elias / Vadasz, Zahava

    Allergy

    2019  Volume 75, Issue 2, Page(s) 481–483

    MeSH term(s) Animals ; Asthma/blood ; Asthma/drug therapy ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Eosinophils/immunology ; Humans ; Lung/immunology ; Lung/pathology ; Mice ; Mice, Inbred BALB C ; Neovascularization, Physiologic/drug effects ; Neutrophils/immunology ; Recombinant Proteins/blood ; Recombinant Proteins/therapeutic use ; Semaphorin-3A/administration & dosage ; Semaphorin-3A/blood ; Semaphorin-3A/pharmacology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors
    Chemical Substances Recombinant Proteins ; SEMA3A protein, human ; Semaphorin-3A ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse
    Language English
    Publishing date 2019-10-20
    Publishing country Denmark
    Document type News
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14026
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    Uh III Zs.150: Show issues Location:
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  8. Article ; Online: Innate immune-responses and their role in driving autoimmunity.

    Toubi, Elias / Vadasz, Zahava

    Autoimmunity reviews

    2019  Volume 18, Issue 3, Page(s) 306–311

    Abstract: Autoimmunity and autoimmune diseases were always considered to be driven mainly by adaptive immune responses, namely by auto-reactive B and T cell over-activity. The continuous stimulation of dendritic cells by autoantigens increases B cell activity, ... ...

    Abstract Autoimmunity and autoimmune diseases were always considered to be driven mainly by adaptive immune responses, namely by auto-reactive B and T cell over-activity. The continuous stimulation of dendritic cells by autoantigens increases B cell activity, driving auto-reactive B cells to increase the production of autoantibodies and of pro-inflammatory cytokines. On the other hand, a subset of dendritic cells is established being of tolerogenic properties thus becoming important in maintaining self-tolerance. However, early innate immune responses are continuously appreciated to be highly important in the development of immune-mediated inflammation in general and autoimmunity in particular. The innate immune system is a complex network of structured cells/proteins such as antigen presenting cells (macrophages and dendritic cells), the complement cascade, and many receptors/cytokines/proteins. Of these, one may mention the high expression of toll-like receptors 7 and 9 in antigen presenting cells, and B cells of systemic lupus erythematosus patients contributing to the expansion of auto-reactive B cells. C-reactive protein (CRP) and C1q are crucially important for efficient uptake of apoptotic cells. However, CRP is appreciated to have a role in maintaining anti-inflammatory responses and in altering autoimmunity. Natural killer cells (NK) are responsible for cytotoxicity responses but some of them (mainly CD56high), are important in maintaining peripheral self-tolerance, thus considered to be immune-regulatory cells. In this review we will cover most of the new data on innate immune system and discuss its importance in the development of autoimmunity. New treatments were developed following our better understanding of these pathways, the targeting of which, opened new therapeutic avenues in treating autoimmune diseases.
    MeSH term(s) Animals ; Autoimmunity ; C-Reactive Protein/immunology ; Complement C1q/immunology ; Humans ; Immunity, Innate ; Killer Cells, Natural/immunology ; Toll-Like Receptors/immunology
    Chemical Substances Toll-Like Receptors ; Complement C1q (80295-33-6) ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2019-01-11
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2144145-5
    ISSN 1873-0183 ; 1568-9972
    ISSN (online) 1873-0183
    ISSN 1568-9972
    DOI 10.1016/j.autrev.2018.10.005
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    Zs.A 5913: Show issues Location:
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  9. Article ; Online: Hemostasis in Allergy.

    Vadasz, Zahava / Toubi, Elias

    Seminars in thrombosis and hemostasis

    2018  Volume 44, Issue 7, Page(s) 669–675

    Abstract: The involvement of the hemostatic system in immune-mediated inflammation is widely reported. Many coagulation factors play a role in the pathogenesis of autoimmune diseases, such as systemic vasculitis and systemic lupus erythematosus. Hemostatic ... ...

    Abstract The involvement of the hemostatic system in immune-mediated inflammation is widely reported. Many coagulation factors play a role in the pathogenesis of autoimmune diseases, such as systemic vasculitis and systemic lupus erythematosus. Hemostatic disorders are also involved in asthma and chronic spontaneous urticaria (CSU). Factor XIIa (FXIIa) was one of the first coagulation factors implicated in inducing both humoral and cellular responses and is therefore considered a prime new therapeutic target in immune-mediated inflammation. The involvement of coagulation factors, such as tissue factor and fibrinogen, in the pathogenesis of asthma has been reported. The finding of platelet activation in asthma also indicates a link between bronchial inflammation and hemostasis. The pathogenesis of mast cell degranulation and CSU was also shown to be associated with the activation of hemostatic factors such as fibrinogen and FXIIa. Increased plasma levels of D-dimer have been widely reported as a biological marker for the duration and severity of CSU. In addition, endothelial-induced cell activation by the kallikrein-high molecular weight complex and the release of heat shock protein 90 was shown to be involved in mast cell degranulation disorders. In this narrative review, the authors aim to summarize the role of hemostasis in inflammation, asthma, and CSU by focusing on the increasing information linking hemostatic factors and immune-mediated disorders.
    MeSH term(s) Biomarkers/blood ; Cell Degranulation/immunology ; Endothelium, Vascular/immunology ; Endothelium, Vascular/metabolism ; Factor XIIa/immunology ; Factor XIIa/metabolism ; Fibrin Fibrinogen Degradation Products/immunology ; Fibrin Fibrinogen Degradation Products/metabolism ; Fibrinogen/immunology ; Fibrinogen/metabolism ; HSP90 Heat-Shock Proteins/blood ; HSP90 Heat-Shock Proteins/immunology ; Hemostasis/immunology ; Humans ; Hypersensitivity/blood ; Hypersensitivity/immunology ; Inflammation/blood ; Inflammation/immunology ; Kallikreins/blood ; Kallikreins/immunology ; Mast Cells/immunology ; Mast Cells/metabolism
    Chemical Substances Biomarkers ; Fibrin Fibrinogen Degradation Products ; HSP90 Heat-Shock Proteins ; fibrin fragment D ; Fibrinogen (9001-32-5) ; Kallikreins (EC 3.4.21.-) ; Factor XIIa (EC 3.4.21.38)
    Language English
    Publishing date 2018-06-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 196901-8
    ISSN 1098-9064 ; 0094-6176
    ISSN (online) 1098-9064
    ISSN 0094-6176
    DOI 10.1055/s-0038-1648232
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    Zs.A 1259: Show issues Location:
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  10. Article: Updates in Rheumatology and Autoimmunity in the Israel Medical Association Journal (IMAJ) 2018.

    Toubi, Elias / Vadasz, Zahava

    The Israel Medical Association journal : IMAJ

    2018  Volume 20, Issue 10, Page(s) 645–648

    MeSH term(s) Autoimmune Diseases/therapy ; Autoimmunity ; Humans ; Israel ; Periodicals as Topic ; Rheumatic Diseases/therapy ; Rheumatology
    Language English
    Publishing date 2018-11-21
    Publishing country Israel
    Document type Journal Article ; Review
    ZDB-ID 2008291-5
    ISSN 1565-1088 ; 0021-2180
    ISSN 1565-1088 ; 0021-2180
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