The Role of T Follicular Helper Cells and T Follicular Regulatory Cells in the Pathogenesis of Autoimmune Hemolytic Anemia

Gao, Yuhan; Jin, Haiqiang; Nan, Ding; Yu, Weiwei; Zhang, Jianhua; Yang, Ying; Hou, Ruiqin; Qin, Ran-ran; Hao, Hongjun; Sun, Ying; Tian, Wenqin

doi:10.1038/s41598-019-56365-3

Cited by 17 publications

(12 citation statements)

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“…It was demonstrated that the immune dysregulation present in AIHA may be associated with specific cytokine gene polymorphisms, which may then result in a Th17/Tregs imbalance [41][42][43]. Recent research into the AIHA mouse model has demonstrated the role of T follicular helper cells (Tfh) and T follicular regulatory cells (Tfr) in participating in B cell differentiation and regulation of anti-RBC antibody production [44]. The results of a recent study revealed that AIHA is also associated with the presence of clonal expansions of CD8+ T cells, yet the immune clones persisted during remission of AIHA and did not correlate with disease severity, duration, nor hemoglobin level, and were probably induced and accumulated during the autoimmune process [45].…”

Section: Pathogenesis Of Aihamentioning

confidence: 99%

Autoimmune hemolytic anemia: current knowledge and perspectives

et al. 2020

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Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

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Section: Pathogenesis Of Aihamentioning

confidence: 99%

Autoimmune hemolytic anemia: current knowledge and perspectives

et al. 2020

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“…Thus, a lower MCHC and higher Ret suggest that patients with primary w-AIHA may have a higher risk of early recurrence. As an autoimmune disease, it is expected that immune cells play an important role in the pathogenesis and progression of AIHA (32,33). However, early clinical works did not pay sufficient attention to immunologically relevant indicators, such as absolute counts of lymphocyte subpopulations and serum immune factor levels.…”

Section: Discussionmentioning

confidence: 99%

Type O blood, the MCHC, and the reticulocyte count impact the early recurrence of primary warm-antibody autoimmune hemolytic anemia in children: A retrospective cohort analysis

et al. 2022

Front. Pediatr.

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ObjectivePrimary warm-antibody autoimmune hemolytic anemia (w-AIHA) is prone to recurrence in children. In this study, we aimed to identify risk indicators for the early recurrence of primary w-AIHA and construct an effective recurrence risk assessment model.MethodsThis was a retrospective cohort study. The clinical data of patients hospitalized with primary w-AIHA in the Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, between 1 January 2018 and 30 September 2021, were collected at the initial diagnosis. Univariate and multivariate logistic regression analyses were used to determine risk indicators for the early recurrence of primary w-AIHA in children, and ROC curve and Kaplan–Meier survival analyses were used for verification. Finally, a risk assessment model for early recurrence in children with primary w-AIHA was constructed using Cox regression and visualized using a nomogram. The model was also verified internally and externally.ResultsThis study included 62 children with primary w-AIHA. Of which, 18 experienced recurrence 1 year after the initial diagnosis. The univariate and multivariate logistic regression analyses showed that type O blood and the reticulocyte count (Ret) were risk indicators for the early recurrence of pediatric primary w-AIHA (P = 0.009, 0.047, respectively). The mean corpuscular hemoglobin concentration (MCHC) is a protective factor (P = 0.040). According to the ROC curve and Kaplan–Meier survival analyses, children with primary w-AIHA whose blood type was O or had an MCHC of <313.5 pg/fL or a Ret of ≥0.161×1012/L had a higher risk of early recurrence (HR = 2.640, 4.430 and 4.450, respectively, and P = 0.040, 0.015 and 0.018, respectively). The blood types (O), MCHCs, and Rets of 56 patients were incorporated into the Cox regression model, and the recurrence risk assessment model for children with primary w-AIHA was successfully constructed and visualized using a nomogram. The calibration curves and decision-curve analysis (DCA) suggested that the risk model has clinical applicability and effectiveness.ConclusionChildren with type O blood and an MCHC value of <313.5 pg/fL or a Ret value of ≥0.161×1012/L have a higher risk of early recurrence. The risk assessment model for the early recurrence of pediatric primary w-AIHA constructed in this study has good clinical applicability and effectiveness.

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“…Sixty-five mice were selected and randomly divided into normal control group, model group. We established AIHA mouse models using classical rat erythrocyte intraperitoneal immunization [ 20 , 21 ]. After adaptive feeding for one-week, healthy female C57BL/6J mice (age, 6–8 weeks; weight, 20–25 g) were weighed, then blood was collected from the inner canthus.…”

Section: Methodsmentioning

confidence: 99%

Iron metabolism abnormalities in autoimmune hemolytic anemia and Jianpishengxue keli can ameliorate hemolysis and improve iron metabolism in AIHA mouse models

et al. 2022

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Objective Autoimmune hemolytic anemia (AIHA) is rare heterogeneous disorder characterized by red blood cell (RBC) destruction via auto-antibodies, and after RBC is destroyed, proinflammatory danger-associated molecular patterns including extracellular hemoglobin, heme, and iron which causing cell injury. And oxidative stress represents one of the most significant effects of chronic hemolysis. Jianpishengxue keli can improve the symptoms of anemia patients with kidney disease and tumors and are beneficial in promoting recovery from chronic inflammation. Therefore, it is presumed that Jianpishengxue keli can improve the symptoms of AIHA. We aimed to investigate iron metabolism in AIHA and effects of Jianpishengxue keli on AIHA murine model. Methods Nineteen hemolytic episode AIHA patients, 10 remission patients and 10 healthy controls (HCs) were enrolled in this study. Serum hepcidin, ferritin and other related indicators of iron metabolism were measured. Mouse models of AIHA were established and received high, medium, or low doses of Jianpishengxue keli by gavage daily for 14 and 28 days respectively. The level of RBCs, Hb, bilirubin, LDH, hepcidin, and the expression level of hepcidin mRNA, and hepatic ferroportin 1(FPN1) protein were evaluated. Results Serum hepcidin in hemolytic episode AIHA patients and remission patients were significantly higher than that in HCs ( p = 0.0083 and p = 0.0473, respectively). Serum ferritin in hemolytic AIHA patients was significantly higher than that in HCs ( p = 0.008). Serum transferrin saturation levels are increased in patients with AIHA[ (57.21 ± 8.96) %]. EPO in hemolytic group was higher than that in healthy control ( p ＜0.05). In AIHA mouse models, IBIL decreased after 14 days of high dose drug intervention. After 28 days, TBIL and IBIL both significantly decreased in all dose groups and LDH significantly decreased in the medium-and high-dose groups. Body weight improved, and the level of RBCs, Hb and hepcidin in the high-dose group returned to normal. After 14 and 28 days of intervention, hepatic hepcidin mRNA in all dose group significantly decreased. Hepatic FPN1 protein which were significantly lower in the AIHA mouse models, increased in all dose groups after drug intervention for 28 days. Conclusion Iron metabolism abnormalities exists in AIHA patients and Jianpishengxue keli can ameliorate hemolysis and improve iron metabolism in AIHA mouse models. KEY MESSAGES Iron metabolism abnormalities exists in hemolytic episode AIHA patients. Hepcidin and ferritin levels significantly elevated and also correlated with the severity of AIHA patients. Jianpishe...

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The Role of T Follicular Helper Cells and T Follicular Regulatory Cells in the Pathogenesis of Autoimmune Hemolytic Anemia

Cited by 17 publications

References 46 publications

Autoimmune hemolytic anemia: current knowledge and perspectives

Autoimmune hemolytic anemia: current knowledge and perspectives

Type O blood, the MCHC, and the reticulocyte count impact the early recurrence of primary warm-antibody autoimmune hemolytic anemia in children: A retrospective cohort analysis

Iron metabolism abnormalities in autoimmune hemolytic anemia and Jianpishengxue keli can ameliorate hemolysis and improve iron metabolism in AIHA mouse models

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