Developing role of B cells in the pathogenesis and treatment of chronic GVHD

Li, Xiaoping; Gao, Qiangguo; Feng, Yimei; Zhang, Xi

doi:10.1111/bjh.15719

Cited by 32 publications

(16 citation statements)

References 106 publications

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“…Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been shown to induce apoptosis of both activated and irregular lymphocytes to promote tolerance (2,3). Consequently, SRL has emerged as one of the most promising immunosuppressive agents after transplantation of either solid organs or allogeneic stem cells (4).…”

Section: Introductionmentioning

confidence: 99%

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

et al. 2020

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Immune thrombocytopenia (ITP) is an autoimmune disease which arises due to self-destruction of circulating platelets. Failure to respond or maintain a response to first-line treatment can lead to refractory/relapsed (R/R) ITP. The mechanism remains complicated and lacks a standard clinical treatment. Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Accordingly, we initiated an open-label, prospective clinical trial using SRL for patients with R/R ITP (ChiCTR-ONC-17012126). The trial enrolled 86 patients, each dosed with 2-4 mg/day of SRL. By the third month, 40% of patients (34 of 86) achieved complete remission (CR) and 45% of patients (39 of 86) achieved partial remission (PR), whereby establishing an overall response rate (ORR) of 85%. By 6 months of treatment, 41% of patients (32 of 78) achieved CR and 29% of patients (23 of 78) achieved PR, establishing an ORR of 70% without serious side effects. After 12 months follow-up, the ORR remained at 65%. We also found that SRL treatment exhibited higher efficacy in achieving CR in ITP patients who were younger than 40 years old or steroid dependent by univariate analysis. Importantly, in patients who responded, SRL treatment was associated with a reduction in the percentage of Th2, Th17 cells, and increase in the percentage of M-MDSCs and Tregs, indicating that SRL may reestablish peripheral tolerance. Taken together, Sirolimus demonstrated efficacy as a second-line agent for R/R ITP.

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Section: Introductionmentioning

confidence: 99%

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

et al. 2020

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“…Furthermore, these studies were generally hampered by the development of graft versus host disease (GVHD) that arises in the context of MHC mismatch between donor and recipient cells. As it turns out, GVHD per se can cause the production of autoantibodies, confounding interpretations [ 20 , 21 ]. Other limitations observed in this model were the high numbers of mouse NK cells, which can directly limit human cell engraftment.…”

Section: Development and Improvement Of Human Immune System Micementioning

confidence: 99%

The development of human immune system mice and their use to study tolerance and autoimmunity

Costa

Lang

Torres

et al. 2019

Journal of Translational Autoimmunity

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Autoimmune diseases evolve from complex interactions between the immune system and self-antigens and involve several genetic attributes, environmental triggers and diverse cell types. Research using experimental mouse models has contributed key knowledge on the mechanisms that underlie these diseases in humans, but differences between the mouse and human immune systems can and, at times, do undermine the translational significance of these findings. The use of human immune system (HIS) mice enables the utility of mouse models with greater relevance for human diseases. As the name conveys, these mice are reconstituted with mature human immune cells transferred directly from peripheral blood or via transplantation of human hematopoietic stem cells that nucleate the generation of a complex human immune system. The function of the human immune system in HIS mice has improved over the years with the stepwise development of better models. HIS mice exhibit key benefits of the murine animal model, such as small size, robust and rapid reproduction and ease of experimental manipulation. Importantly, HIS mice also provide an applicable in vivo setting that permit the investigation of the physiological and pathological functions of the human immune system and its response to novel treatments. With the gaining popularity of HIS mice in the last decade, the potential of this model has been exploited for research in basic science, infectious diseases, cancer, and autoimmunity. In this review we focus on the use of HIS mice in autoimmune studies to stimulate further development of these valuable models.

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“…R Z et al [29] rituxan is studied in combination with large dose of chemotherapy in patients with NHL APBSCT treatment effect, the research object and Ⅳ follicular Ⅲ CD cells infusion, and to rebuild hematopoietic stem cells ability between the two groups, clinical adverse reactions and no obvious difference. X L et al [30] also confirmed that combined chemotherapy with rituximab could significantly reduce the contamination of lymphoma cells in mobilized stem cells, and the clinical and molecular remission rates of patients in the rituximab group were also significantly higher than those in the control group. Galimberti et al [31] 23 cases of follicular non-hodgkin's lymphoma patients APBSCT, including 13 cases with CHOP plan after chemotherapy in patients with high-dose chemotherapy alone, ll patients using high doses of chemotherapy in combination with rituxan treatment, the results showed that application of rituxan treatment group of Bel-2/IgH rearrangement negative rate was 86%, compared with high-dose chemotherapy control graft Bel-2/IgH rearrangement negative rate is 14.3%, the former EFS 5 years was 100%, and the lat-Open Journal of Blood Diseases ter is only 41%, This suggests that rituximab is an effective treatment for patients with follicular non-Hodgkin's lymphoma.…”

Section: Application Of Rituximab In Hematopoietic Stem Cell Transplamentioning

confidence: 86%

Progress in the Treatment of Hematological Diseases with Rituximab

Fu¹,

Lin²,

Yao³

et al. 2021

OJBD

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Rituximab is a mouse and human chimeric CD 20 (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD 20 antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD 20 molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.

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Developing role of B cells in the pathogenesis and treatment of chronic GVHD

Cited by 32 publications

References 106 publications

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

The development of human immune system mice and their use to study tolerance and autoimmunity

Progress in the Treatment of Hematological Diseases with Rituximab

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