المؤلفون: Sanz, Iñaki¹ ignaciosanz@urrnc.rochester.edu, Lee, Eun-Hyung², Sanz, Iñaki¹ (AUTHOR), Lee, F Eun-Hyung (AUTHOR)

المصدر: Nature Reviews Rheumatology. Jun2010, Vol. 6 Issue 6, p326-338. 13p. 1 Diagram, 1 Chart, 3 Graphs.

مصطلحات موضوعية: *B cells, *TARGET organs (Anatomy), *SYSTEMIC lupus erythematosus, *AUTOIMMUNE diseases, *TUMOR necrosis factors, *RITUXIMAB, *CLINICAL trials, *BIOTHERAPY, *RESEARCH funding

مستخلص: The use of B-cell targeted therapies for the treatment of systemic lupus erythematosus (SLE) has generated great interest owing to the multiple pathogenic roles carried out by B cells in this disease. Strong support for targeting B cells is provided by genetic, immunological and clinical observations that place these cells at the center of SLE pathogenesis, as initiating, amplifying and effector cells. Interest in targeting B cells has also been fostered by the successful use of similar interventions to treat other autoimmune diseases such as rheumatoid arthritis, and by the initial promise shown by B-cell depletion to treat SLE in early studies. Although the initial high enthusiasm has been tempered by negative results from phase III trials of the B-cell-depleting agent rituximab in SLE, renewed vigor should be instilled in the field by the convergence of the latest results using agents that inhibit B-cell-activating factor (BAFF, also known as BLyS and tumor necrosis factor ligand superfamily, member 13b), further analysis of data from trials using rituximab and greatly improved understanding of B-cell biology. Combined, the available information identifies several new avenues for the therapeutic targeting of B cells in SLE. [ABSTRACT FROM AUTHOR]

المؤلفون: Garcia De Vinuesa, Maria Carola, Sanz, Inaki, Cook, Matthew

المصدر: Nature Reviews Immunology

مصطلحات موضوعية: Keywords: antigen, antinuclear antibody, autoantibody, cardiolipin, CD40 antigen, CD40 ligand, double stranded DNA, glucose 6 phosphate isomerase, intercellular adhesion molecule 1, interleukin 21 receptor, interleukin 4, protein bcl 6, rheumatoid factor, rituximab

الوصف: In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets.

العلاقة: http://hdl.handle.net/1885/33088Test; https://openresearch-repository.anu.edu.au/bitstream/1885/33088/5/Vinuesa-Cook_NatImm_Dysregulation.pdf.jpgTest; https://openresearch-repository.anu.edu.au/bitstream/1885/33088/7/01_Garcia+De+Vinuesa_Dysregulation_of_germinal_2009.pdf.jpgTest

الإتاحة: https://doi.org/10.1038/nri2637Test
http://hdl.handle.net/1885/33088Test
https://openresearch-repository.anu.edu.au/bitstream/1885/33088/5/Vinuesa-Cook_NatImm_Dysregulation.pdf.jpgTest
https://openresearch-repository.anu.edu.au/bitstream/1885/33088/7/01_Garcia+De+Vinuesa_Dysregulation_of_germinal_2009.pdf.jpgTest

المؤلفون: Sanz, Iñaki¹ ignacio.sanz@emory.edu

المصدر: Nature Reviews Rheumatology. Dec2016, Vol. 12 Issue 12, p700-702. 3p.

مصطلحات موضوعية: *RITUXIMAB, *SYSTEMIC lupus erythematosus treatment, *DISEASE remission, *B cells, *ANTINEUTROPHIL cytoplasmic antibodies

المؤلفون: Ramos-Casals, Manuel¹, Sanz, Iñaki², Bosch, Xavier³ xavbosch@clinic.ub.es, Stone, John H.⁴, Khamashta, Munther A.⁵

المصدر: American Journal of Medicine. Apr2012, Vol. 125 Issue 4, p327-336. 10p.

مصطلحات موضوعية: *SYSTEMIC lupus erythematosus treatment, *B cells, *THERAPEUTIC use of monoclonal antibodies, *CLINICAL trials, *DATA analysis, *TREATMENT effectiveness

مستخلص: Abstract: The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus. [Copyright &y& Elsevier]

المؤلفون: Sanz, Iñaki

المصدر: Drug Discovery Today: Therapeutic Strategies; Mar2009, Vol. 6 Issue 1, p13-19, 7p

مصطلحات موضوعية: CLINICAL indications, RITUXIMAB, AUTOIMMUNE diseases, B cells, RHEUMATOID arthritis, MULTIPLE sclerosis, DIABETES, T cells

مستخلص: B cell targeted therapies are becoming widespread for the treatment of multiple autoimmune diseases including conditions such as Rheumatoid Arthritis, Multiple Sclerosis and Type ! diabetes typically considered as T cell mediated. This interest stems from the convergence of tremendous progress in understanding the multiple effector and regulatory roles played by B cells in regulating autoimmunity as well as in the promising results reported for B cell depletion in an ever expanding number of autoimmune diseases. This review will review current knowledge of Rituximab-induced B cell depletion in diseases where this therapy is either well established or represents a promising therapeutic avenue with potential to uncover important disease mechanisms. [Copyright &y& Elsevier]

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المؤلفون: Anolik, Jennifer H., Barnard, Jennifer, Owen, Teresa, Bo Zheng, Kemshetti, Sunil, Looney, R. John, Sanz, Iñaki

المصدر: Arthritis & Rheumatism; Sep2007, Vol. 56 Issue 9, p3044-3056, 13p, 1 Diagram, 2 Charts, 3 Graphs

مصطلحات موضوعية: RITUXIMAB, SYSTEMIC lupus erythematosus, CYTOMETRY, B cells, AUTOIMMUNE diseases

مستخلص: The article discusses a study which examined the magnitude, duration and cause of defects in rituximab-treated systemic lupus erythematosus (SLE) patients. Using multicolor flow cytometry, the authors assessed the B cells taken from the peripheral blood and tonsils of SLE patients. They observed heterogeneity in the B cell depletion and reconstitution process that impacts the clinical and immunologic outcomes in SLE.

المؤلفون: Sanz, Iñaki¹ ignacio_sanz@urmc.rochester.edu, Sanz, Iñaki (AUTHOR)

المصدر: Nature Reviews Rheumatology. Jun2009, Vol. 5 Issue 6, p304-305. 2p. 3 Black and White Photographs.

مصطلحات موضوعية: *DRUG efficacy, *RITUXIMAB, *ADRENOCORTICAL hormones, *SYSTEMIC lupus erythematosus treatment, *LUPUS nephritis, *B cells, *LYMPHOID tissue, *THERAPEUTICS

مستخلص: Two consecutive trials of rituximab, a B-cell-depleting anti-CD20 monoclonal antibody, have threatened the future of B-cell-targeted therapy for systemic lupus erythematosus (SLE). While rumors of the demise of this approach might be greatly exaggerated, the outcomes of these studies should force academics and the pharmaceutical industry back to the drawing board. [ABSTRACT FROM AUTHOR]

المؤلفون: Anolik, Jennifer H. jennifer_anolik@urmc.rochester.edu, Friedberg, Jonathan W.¹, Zheng, Bo¹, Barnard, Jennifer¹, Owen, Teresa¹, Cushing, Emily¹, Kelly, Jennifer¹, Milner, Eric C.B.¹, Fisher, Richard I.¹, Sanz, Iñaki¹

المصدر: Clinical Immunology. Feb2007, Vol. 122 Issue 2, p139-145. 7p.

مصطلحات موضوعية: *B cells, *RITUXIMAB, *LYMPHOMAS, *IMMUNOLOGY, *IMMUNE system, *BONE marrow transplantation

مستخلص: Abstract: The long-term immunologic effects of B cell depletion with rituximab and the characteristics of the reconstituting B cell pool in lymphoma patients are not well defined, despite the widespread usage of this therapy. Here we report that during the B cell reconstitution phase a majority of the peripheral blood B cells have an immature transitional phenotype (47.8%±25.2% vs. 4.4%±2.4% for normal controls, p <0.0001), similar to what has been described during the original ontogeny of the immune system and following bone marrow transplantation. Moreover, the recovery of the CD27+ memory B cell pool was delayed compared to normal B cell ontogeny, remaining below normal controls at 1 year post-rituximab (4.4%±3% vs. 31%±7%, p <0.0001). Expansion of functionally immature B cells and decreased memory B cells may contribute to an immunodeficient state in patients recovering from rituximab mediated B cell depletion, particularly with repeated treatment. [Copyright &y& Elsevier]