Roles of regulatory T cells in the pathogenesis of pediatric aplastic anemia

Lin, Shaofen; Hou, Lele; Liu, Su; Wang, Jian; Chen, Qihui; Zhang, Bihong; Hou, Xue; Huang, Junbin; Chen, Chun

doi:10.1080/08880018.2019.1621968

Cited by 9 publications

(17 citation statements)

References 21 publications

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“…Tregs have reported to be decreased in AA, both in the peripheral blood and bone marrow, compared with healthy controls 52,191,192 . Moreover, the likelihood to respond to treatment appeared to be higher for patients with an increased number of Tregs at diagnosis 49,52 . However, our data indicate that the number of Tregs in the bone marrow of AA patients is not predictive for the response to ATG therapy.…”

Section: Discussionmentioning

confidence: 98%

“…Another important aspect involves regulatory T cells (Tregs), which are decreased in AA. There are some indications that the number of Tregs or a unique subtype of Tregs is correlated with the response to ATG treatment, and Tregs appear to increase with the response to treatment [47][48][49] . Interleukin (IL)-17-producing CD4 + cells (Th17) play a pivotal role in autoimmunity 50 , and although AA does not share many similarities with autoimmune diseases, Th17 cells are increased (SAA) and seem to play a role during the early stage of AA 51,52 .…”

Section: Immunological Mechanismsmentioning

confidence: 99%

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High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Vaht

Göransson

Carlson

et al. 2019

Biology of Blood and Marrow Transplantation

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Background and aims. Aplastic anemia (AA) is a rare but life-threatening disease. The introduction of immunosuppressive treatment (IST) and hematopoietic stem cell transplantation (HSCT) has considerably improved the outcome of patients with AA. However, modern-day population-based data are limited. This thesis aimed to retrospectively analyze the incidence, treatment modalities, survival, and immune markers in the bone marrow of patients diagnosed with AA in Sweden from 2000-2011. Patients and methods. Patients were included via the National Patient Registry and diagnosed according to the Camitta criteria. All data were collected from medical charts. In paper IV, immunohistochemistry was used to obtain data on regulatory T cells and macrophages in the bone marrow. Results and conclusions. We identified 257 confirmed cases, with an overall incidence of 2.35 cases per million inhabitants per year. The 5-year overall survival (OS) was >90% in patients aged up to 39 years but 38.1% in patients aged ≥60 years. Multivariate analysis showed that age ≥40 years, very severe AA, and no specific therapy were independent risk factors for inferior survival. First-line IST treated patients (n=158) showed a 47% response rate with no difference regarding the age groups or anti-thymocyte globulin (ATG) formulation. The response was significantly associated with the severity grade at the time of treatment initiation, and very severe AA patients exhibited a response rate of 22%. Sixty-eight patients underwent HSCT with a 5-year OS of 86.8%. The graft-versus-host-disease-free, relapse/rejection-free survival at 5 years was 69.1%. Patients aged ³40 years had higher transplant-related mortality that translated into a lower 5-year OS. In paper IV, we found lower numbers of FOXP3-positive regulatory T cells in AA patients without predictive value for IST response and that patients with a higher number of CD163-positive macrophages had a better 5-year OS, but this benefit was only observed in the non-severe AA group. In conclusion, younger patients have very good long-term survival regardless of the choice of therapy, whereas the outcome for patients ≥60 years remains poor. Very severe AA patients respond poorly to ATG, which indicates the need for a different treatment approach.

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Section: Discussionmentioning

confidence: 98%

Section: Immunological Mechanismsmentioning

confidence: 99%

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Vaht

Göransson

Carlson

et al. 2019

Biology of Blood and Marrow Transplantation

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“…T reg cells were defined as CD4+CD25+foxP 3 + coexpression and expressed as a percentage of the total CD4+ T population. 12,13 Only 31 patients gave consent for the measurement of T reg cells before and after FK treatment. We recruited eight age-and gender-matched healthy volunteers and tested their T reg cells as normal controls.…”

Section: Examination Of Regulatory T Cellsmentioning

confidence: 99%

Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study

Huang

Zhou

et al. 2020

DDDT

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Background: For symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) may be an option if these patients do not respond or become tolerant to cyclosporine A (CsA). Methods: We enrolled 101 NSAA patients who were refractory or intolerant to CsA with no chance of HSCT or ATG treatment and treated these patients with tacrolimus for at least 6 months, with follow-up for at least one year. Results: The overall response rate (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%), and the median time to optimal response was 6 (3～10) months. Thirtytwo (31.7%) cases had elevated creatinine levels. Eight (7.9%) cases had elevations in AST/ ALT. A total of 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12 ng/mL, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cell levels pre-FK treatment were much lower than those of healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004) but increased significantly after FK treatment (3.7±0.6% vs 7.1±0.8%, P=0.0039). Conclusion: Our data suggest that tacrolimus is a salvage treatment for patients with NSAA that is refractory or intolerant to CsA.

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“…Total events of 50 000 were gated based on forward (FSC) and side-scatter (SSC) characteristics and dot plots for T reg cells were gated on CD4+cells. T reg cells were de ned as CD4+CD25+foxP 3 + co-expression and expressed as a percentage of total CD4+ T population [12,13]. Only 31 patients gave their consent to measure T reg cells before and after FK treatment.…”

Section: Examination Of Regulatory T Cellsmentioning

confidence: 99%

Effective treatment with tacrolimus for patients with non-severe aplastic anemia refractory/ intolerant to cyclosporine A: a retrospective study

Du¹,

Huang²,

Zhou³

et al. 2020

Preprint

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Background: For the symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) was occasionally reported to be an option if they were not response or tolerant to the cyclosporine A (CsA). Method: We collected and analyzed respectively 101 NSAA patients refractory or intolerant to CsA with no chance of HSCT or ATG, and treated them with tacrolimus for at least 6 months and followed up for at least one year. Results: The overall response (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%) and the median time to optimal response was 6 (3～10) months. 32 (31.7%) cases had elevated creatinine level. 8 (7.9%) cases had elevation of AST/ALT. 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12ng/ml, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cells level pre-FK treatment was much lower than healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004), but increased significantly after FK treatment (3.7±0.6% vs. 7.1±0.8%, P=0.0039). Conclusion: Our data provide a possibility of tacrolimus as a salvage treatment for patients with NSAA refractory or intolerant to CsA.

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Roles of regulatory T cells in the pathogenesis of pediatric aplastic anemia

Cited by 9 publications

References 21 publications

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study

Effective treatment with tacrolimus for patients with non-severe aplastic anemia refractory/ intolerant to cyclosporine A: a retrospective study

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