Tacrolimus is effective in relapsed/refractory autoimmune cytopenias: results of a single-center retrospective study

Du, Yali; Yang, Chen; Chen, Miao; Ruan, Jing; Huang, Yuzhou; Chen, Fangfei; Han, Bing

doi:10.1080/16078454.2020.1852763

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…Retrospective data from patients with ITP who were refractory to corticosteroids/ relapsed and treated with tacrolimus showed that the overall response rate was 63.6% and the complete response rate was 30.3%. 13 These findings indicated that tacrolimus might be a novel approach for ITP. However, the underlying mechanism is poorly defined and needs to be explored further.…”

Section: Abstract Adiponectin Complement Mesenchymal Stem Cells Nlrp3...mentioning

confidence: 95%

Tacrolimus prevents complement‐mediated Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia

Cai

et al. 2022

Br J Haematol

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SummaryThe abnormal immunomodulatory functions of mesenchymal stem cells (MSCs) have been implicated in the development of immune thrombocytopenia (ITP). Recent studies have suggested important effects of complement on immune cell function. However, whether complement modulates bone marrow MSCs function in ITP is poorly defined. Tacrolimus has recently been applied to the treatment of autoimmune diseases. Here, we explored whether impaired ITP‐MSCs could be targeted by tacrolimus. Our results showed that the Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome was activated in ITP MSCs with complement deposition (MSCs‐C+) and initiated caspase‐1‐dependent pyroptosis. Transcriptome sequencing results showed abnormal fatty acid metabolism in MSCs‐C+. Enhanced fatty acid β‐oxidation and reactive oxygen species production activated the NLRP3 inflammasome. Adipocytes derived from MSCs‐C+ secreted less adiponectin. Adiponectin promoted the differentiation of megakaryocytes and inhibited the destruction of platelets. Tacrolimus inhibited NLRP3 inflammasome activation and MSCs‐C+ pyroptosis in vitro and in vivo. Tacrolimus plus danazol elicited a higher sustained response than danazol monotherapy in corticosteroid‐resistant patients with ITP. Our findings demonstrate that the activation of the NLRP3 inflammasome in ITP MSCs mediated by complement could be inhibited by tacrolimus, which might be a potential new therapy for ITP.

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Section: Abstract Adiponectin Complement Mesenchymal Stem Cells Nlrp3...mentioning

confidence: 95%

Tacrolimus prevents complement‐mediated Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia

Cai

et al. 2022

Br J Haematol

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“…The response criteria were defined as follows (8,10). A complete response (CR) was defined as a platelet count ≥100×10 9 /L and no bleeding.…”

Section: Response Criteriamentioning

confidence: 99%

“…analysis of platelet counts at baseline and after 4 weeks, 8 weeks, 12 weeks and 24 weeks of TAC treatment. Disease activity for pSS patients was assessed by the authors using the European SS Disease Activity Index (ESS-DAI) score (8).…”

Section: Clinical and Immunological Assessmentsmentioning

confidence: 99%

“…TAC mainly plays an immunosuppressive role by inhibiting the activity of helper T (Th) cells and reducing the release of interleukin (IL)-2. In the past few years, TAC has been widely used in the treatment of a variety of rheumatic diseases and has shown a good therapeutic effect (5)(6)(7)(8). However, there are no data on the efficacy and safety of TAC in patients with RITP secondary to pSS.…”

Section: Introductionmentioning

confidence: 99%

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Tacrolimus therapy in primary Sjögren's syndrome with refractory immune thrombocytopenia: a retrospective study

Yan

Gong

et al. 2022

Clinical and Experimental Rheumatology

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ObjectivesTo evaluate the efficacy and safety of tacrolimus (TAC) for the treatment of primary Sjögren's syndrome (pSS) with refractory immune thrombocytopenia (RITP). MethodsTwenty-three pSS patients with RITP treated with TAC from June 2018 to June 2021 at the First Affiliated Hospital of Soochow University were enrolled in this retrospective cohort study. Platelet response, clinical and immunological parameters, toxicity and safety were compared and analysed at baseline and different points after TAC treatment. ResultsAt 4 weeks after treatment, 2 patients (8.7%) attained a complete response (CR, platelet count ≥100×10 9 /L and no bleeding), 15 patients (65.2%) achieved a partial response (PR, platelet count ≥ 30×10 9 /L but <100×10 9 /L and no bleeding or a platelet count at least twice that before treatment), and the other 6 patients (26.1%) did not respond to TAC treatment. At 8 weeks after treatment, a CR was seen in 4 patients (17.4%), and the percentage of patients with a PR increased to 78.3% (18 patients). The percentage of patients with a CR increased to 47.8% (11 patients), and 9 patients (39.1%) achieved a PR without relapse at 12 weeks after treatment. At 24 weeks after treatment, 14 patients (60.9%) achieved a CR, and 8 patients (34.8%) achieved a PR. Compared to before treatment, the level of IgG was decreased significantly at 24 weeks after treatment, whereas there was no significant difference in the levels of IgM or IgA between baseline and 24 weeks after treatment. Additionally, the absolute CD3 + T cell count, European SS Disease Activity Index (ESSDAI) score, and levels of IL-2 and INF-γ were significantly decreased at 24 weeks after treatment. Conclusion TAC is effective and well tolerated by pSS patients with RITP, and the mechanism underlying the effect of TAC in thesepatients may be related to reduced Th1 cytokine expression.

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“…Tacrolimus (a selective T‑cell activation inhibitor, “off label”) is reported in quite a few cases of ITP associated with mostly allogenic transplant recipients. A new retrospective single-center study on the effect of tacrolimus in relapsed or refractory ITP showed an overall response rate of 63.6% (>100 G/l: CR: 30.3%; >30 G/l: PR: 33.3%) [ 22 ].…”

Section: Second-line Treatmentmentioning

confidence: 99%

Practical considerations for the management of immune thrombocytopenic purpura

Fillitz

Dixer

Keil

2021

memo

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Immune thrombocytopenic purpura (ITP) is a rare hematological disorder with an autoimmune-mediated, often dramatic reduction of platelets in peripheral blood. Thrombocytopenia results from a reduced life span of thrombocytes and an additionally decreased production in bone marrow. For decades, the first-line therapy for ITP has been corticosteroids. As significant thrombocytopenic bleedings occur, the use of additional medication may be needed. Recent updates on therapy guidelines recommend the shortest possible use of corticosteroids. Thrombopoietin-receptor agonists are often used second line. Today splenectomy, which was previously recommended after unsuccessful first-line therapy, is usually considered much later. Patients who do not respond even after multiple lines of therapy continue to pose a major challenge. New drugs for ITP treatment are now available after steroid failure and will be discussed. This review gives a short summary on actual therapy guidelines taking into account newly available therapy options. In addition, comparisons between selected published data and experience at our department are made.

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Tacrolimus is effective in relapsed/refractory autoimmune cytopenias: results of a single-center retrospective study

Cited by 10 publications

References 24 publications

Tacrolimus prevents complement‐mediated Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia

Tacrolimus prevents complement‐mediated Nod‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia

Tacrolimus therapy in primary Sjögren's syndrome with refractory immune thrombocytopenia: a retrospective study

Practical considerations for the management of immune thrombocytopenic purpura

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