Efficacy of Low-Dose Rituximab in Primary Immune Thrombocytopenia

Objective:To explore the effect of low-dose rituximab in primary immune thrombocytopenia.Methods:From January 2022 to January 2023,60 patients with primary immune thrombocytopenia were randomly divided into two groups.The control group was treated with standard doses of rituximab,and the observation group was treated with low doses of rituximab.Rituximab was used for treatment,and the clinical curative effect of the two groups was observed.Results:Before treatment,there was no statistically significant difference in platelet count(PLT),anti-GPⅡb/Ⅲa antibody,and anti-GPⅠb/Ⅸantibody between the two groups(P>0.05).After treatment,the PLT of the two groups increased significantly.Antibodies were all decreased,and there was no significant difference between the two groups(P>0.05).The incidence of adverse reactions in the observation group was 13.33%,and that in the control group was 40.00%.The adverse reactions in the observation group were significantly lower than the control group(P<0.05).Conclusion:In the clinical treatment of primary immune thrombocytopenia,low-dose rituximab can control the progression of the disease,improve blood routine indicators,and have fewer adverse reactions.

Helicobacter pylori-associated immune thrombocytopenia:Clinical features and pathogenic mechanisms

Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. There is growing evidence that the eradication of Helicobacter pylori (H. pylori) effectively increases platelet count in a considerable proportion of ITP patients infected with this bacterium. In the majority of ITP patients responding to H. pylori eradication therapy, the anti-platelet autoantibody response is completely resolved with no relapse for more than 7 years, indicating that the disease is cured. Therefore, adult patients with suspected ITP should be examined for H. pylori infection, and eradication therapy is recommended if the infection is present. Notably, however, the efficacy of H. pylori eradication therapy in ITP patients varies widely among countries, with a higher response rate in Japan compared with the United States and European countries other than Italy. The pathogenesis of H. pylori-associated ITP is still uncertain, although the mechanisms are known to involve multiple factors. H. pylori may modulate the Fc&#x003b3;-receptor balance of monocytes/macrophages in favor of activating Fc&#x003b3; receptors, and H. pylori components may mimic the molecular makeup of platelet antigens. Further studies of the pathogenic process of H. pylori-associated ITP may be useful for the development of new therapeutic strategies for ITP.

Visual analysis of research hotspots and trends in the treatment of immune thrombocytopenia with traditional Chinese medicine

Objective Through bibliometrics and visual analysis of the related studies on traditional Chinese medicine(TCM)treatment of immune thrombocytopenia(ITP),this study aims to sort out the overall research progress,hotspots,and trends in this field,and provide reference for further research in ITP.Methods The articles on ITP treated by TCM were retrieved from China National Knowledge Infrastructure(CNKI),Wanfang Database,China Science and Technology Journal Database(VIP),Web of Science Core Collection(WOSCC),and PubMed.The retrieval time was from the establishment of the databases to July 31,2022.VOSviewer,CiteSpace,Carrot2,and Note-Express were used for data analysis of the articles in terms of their quantities,types,and journals,and for visualization of research hotspots,authors,institutions,and keywords.Results 1493 Chinese articles and 40 English articles were included.The articles in Chinese mainly focus on clinical trial research and clinical experience summary,while the English articles mainly focus on clinical trial research and animal research.The Chinese articles were published in 317 Chinese journals,while English articles were published in 29 English journals.Research hotspots include the clinical syndrome differentiation of ITP,the therapeutic effect of TCM compounds on ITP,and the mechanism of ITP treatment.Keyword analysis shows that there are many research achievements in integrated traditional Chinese and western medicine treatment,clinical research,famous doctors’experience,TCM treatment,cellular immunity,and humoral immunity.The authors with the most articles in Chinese and English are Professor CHEN Xinyi and Professor MA Rou,respectively,and the research institutions with the most articles are Dongzhimen Hospital of Beijing University of Chinese Medicine and Xiyuan Hospital of China Academy of Chinese Medical Sciences.Chinese herbs often used to treat ITP clinically include Xianhecao(Agrimoniae Herba),Nvzhenzi(Ligustri Lucidi Fructus),Mohanlian(Ecliptae Herba),Zhongjiefeng(Sarcandrae Herba),etc.,and the prescription usually used to treat ITP include Guipi Decoction(归脾汤),Xijiao Dihuang Decoction(犀角地黄汤),Bazhen Decoction(八珍汤),Erzhi Pill(二至丸),and Xiaochaihu De-coction(小柴胡汤).The main development trends toward retrospective study,TCM treatment mechanism,and data mining.

Study on the Biological Basis of Qi, Blood, and Vessel in Immune Thrombocytopenia Patients With Syndrome of Qi Failing to Govern Blood Based on the Theory of Qi and Blood

Objective: To investigate the biological basis of qi, blood and vessel in immune thrombocytopenia(ITP) patients with syndrome of qi failing to govern blood(SQFGB) based on traditional Chinese medicine.Methods: A total of 52 ITP patients with SQFCB were enrolled and divided into bleeding group(38 cases) and non-bleeding group(14 cases).Bleeding group was further divided into mild qi deficiency group(25 cases) and moderate/severe qi deficiency group(13 cases) based on Chinese Medicine syndrome score.20 healthy volunteer were recruited as control group.The count of platelet(PLT) was taken as the blood related indicator.The expressions of cytokines including IL-1β, IL-17 A, TNF-α, CD40 L, and TGF-β, detected by Aim Plex Multiple Immunoassays for Flow, were taken as the qi related indicators.The expressions of VEGF-A, detected by Aim Plex Multiple Immunoassays for Flow and NO, NOS, and ET-1 detected by ELISA, were taken as the vessel related indicators.Results: As compared to the control group, the count of PLT, taken as the blood related indicator, was significantly lower in ITP group patients with SQFCB(P<0.05).The expression levels of IL-17 A and TNF-α, taken as the qi related indicators, were significantly higher, while those of CD40 L, IL-1β, and TGF-β, also taken as the qi related indicators, were significantly lower in ITP patients with SQFCB, respectively(P<0.05).The expression levels of NO and ET-1, taken as the vessel related indicators, were significantly higher, while the expression levels of NOS and VEGF-A also taken as the vessel related indicators, were significantly lower in ITP patients with SQFCB, respectively(P<0.05).The count of PLT, taken as the blood related indicator, was significantly lower in moderate/severe group than those in mild group(P<0.05).The expression levels of CD40 L and TGF-β, taken as the qi related indicators, were also significantly lower in moderate/severe group than those in mild group, respectively(P<0.05).Conclusion: The count of PLT might be the biological basis of blood.The expressions of NO, NOS, ET-1 and VEGF-A might be the biological basis of vessel.The expressions of IL-1β, IL-17 A, TNF-α, TGF-β, and CD40 L may be the biological basis of qi.The expressions of CD40 L and TGF-β could reflect the degree of qi deficiency in ITP patients based on the theory of qi and blood.

Treatment of immune thrombocytopenia after allogeneic cord blood stem cell transplantation with rituximab: a case report

Immune thrombocytopenia (ITP) is a chronic disease resulting from increased platelet destruction and impaired platelet production. Secondary ITP can be a manifestation of chronic graft-versus-host disease (GVHD) and represent a lymphoproliferative disorder. A boy with chronic graft-versus-host disease after cord blood stem cell transplantation who had severe refractory immune-mediated thrombocytopenia received infusion of rituximab weekly, 375 mg/m2, for 4 weeks. Platelets count of the patient was recovered, and rituximab was well tolerated with no severe toxicity observed during treatment.

Rapid progressive vaccine-induced immune thrombotic thrombocytopenia with cerebral venous thrombosis after ChAdOx1 nCoV-19(AZD1222)vaccination:A case report

BACKGROUND Vaccine-induced immune thrombotic thrombocytopenia(VITT)is a rare and potentially life-threatening condition after receiving coronavirus disease vaccines.It is characterized by symptom onset at 5 to 30 d postvaccination,thrombocytopenia,thrombosis,high D-dimer level,and antiplatelet factor 4(anti-PF4)antibody positivity.VITT can progress very fast,requiring urgent management.Only few studies have described its detailed clinical course and imaging changes.We report a typical VITT case in a patient who underwent regular repeated brain imaging examinations.CASE SUMMARY A young woman presented with headaches at 7 d after the ChAdOx1 nCoV-19vaccine(AZD1222)injection.She then showed progressive symptoms of left upper limb clumsiness.Brain computed tomography revealed venous infarction at the right parietal lobe with a hyperacute thrombus in the cortical vein.Two hours later,brain magnetic resonance imaging revealed hemorrhage at the same area.Magnetic resonance venography showed an irregular contour of the right transverse sinus.Laboratory examination revealed a high D-dimer level,thrombocytopenia,and a high titer for anti-PF4 antibodies.She was treated with anticoagulants,intravenous immunoglobulin,and steroids and analgesic agents were administered for pain control.She had a marked improvement on headaches and clumsiness after treatment along with radiological thrombus resolution.During follow-up at the outpatient department,her modified Rankin scale at 90 d was 1.CONCLUSION Clinicians should be alerted whenever patients present with persistent and progressive headaches or focal motor/sensory deficits postvaccination.

Immune thrombocytopenia in adults

Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >6 mo and requiring therapy to improve the thrombocytopenia.The underlying defects leading to autoantibody production are unknown.Molecular mimicry appears to play a role in the development of self-reactive platelet antibodies after vaccination and certain viral infections.Platelet life span is reduced as a consequence of antibody-mediated clearance by tissue macrophages in essentially all patients.Diagnosis is based on the exclusion of the other causes of thrombocytopenia.Steroid is the first choice of the treatment,often followed by splenectomy in unresponsive cases.Intravenous immunoglobulin,anti-Rho(D) immune globulin,azathioprine,cyclosporine A,cyclophosphamide,danazol,dapsone,mycophenolate mofetil,rituximab,thrombopoietin receptor agonists and vinca alkaloids are other choices of treatment.

Effectiveness of total therapy in immune thrombocytopenia purpura:case series

Immune Thrombocytopenic purpura(ITP)is a haematologicimmune-mediated disorder in which the amount of platelet in the blood decreases abnormally.Single-agent therapies for ITP have not proven successful in achieving long-term remission,with relapse occurring in about half of the patients(p/t).Treatment options which include Rituximab with Dexamethasone as frontline therapy,have durable response rates ranging from 58%to 76%.In this study,we have used‘Total therapy’as treatment which includes low-dose Rituximab in combination with Thrombopoietin receptor agonist(TPO-RA)(Romiplostim)and high-dose Dexamethasone.In this case series study,each patient received romiplostim(250 mcg weekly s/c,4 doses)in combination with low-dose rituximab(100 mg weekly IV,4 doses)and high-dose dexamethasone(40 mgIV on days 1-4and days 15-18).This treatment combination demonstrated rapid response rates and a low rate of side effects,making it a good alternative for individuals with ITP.

Expression and Significance of Regulatory B Cells in Patients with Immune Thrombocytopenia

Objective: To detect the expression and significance of regulatory B cells in patients with immune thrombocytopenia. Methods: 73 ITP patients were divided into glucocorticoids treatment group (n = 42) and recombinant human thrombopoietin (rhTPO) treatment group (n = 31). According to the therapeutic effect, it was divided into effective group and ineffective group. The expression of CD19+ CD24hiCD38hi Breg in peripheral blood was detected by flow cytometry before and after treatment. The expression levels of transforming growth factor (TGF)-β1, interleukin (IL-10) and interferon (IFN)-γ were detected by ELISA before and after treatment. 30 volunteers were selected as the control group. Results: The expression of CD19+ CD24hiCD38hi Breg and cytokines IL-10 and TGF-β1 in 73 ITP patients before treatment was lower than that in the control group, while the expression of IFN-γ was higher than that in the control group (p < 0. 05). The expression levels of CD19+ CD24hiCD38hi Breg, IL-10 and TGF-β1 in the effective group were significantly higher than before treatment, while the expression of IFN-γ was significantly lower than before treatment (p < 0. 05). The expression of CD19+ CD24hiCD38hi Breg, IFN-γ, IL-10 and TGF-β1 in the invalid group had no significant change compared with before treatment. Conclusion: Abnormal expression of CD19+ CD24hiCD38hi Breg and related cytokines is involved in the pathogenesis of ITP.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.

Spotlight on eltrombopag concentration in pediatric immune thrombocytopenia:A single-center observational study in China

Importance:Eltrombopag has been recommended for pediatric immune thrombocytopenia(ITP).Response and adverse drug reactions(ADRs)varied widely between individuals,even at the same dose of eltrombopag.The appropriate eltrombopag concentration in ITP has not been reported.Objective:This study aims to explore the appropriate eltrombopag concentration in pediatric ITP.Methods:This was a single-center,prospective cohort study.Children diagnosed with refractory persistent/chronic ITP and platelet count<30×10^(9)/L were treated with eltrombopag and followed up for at least 2 months.Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag.The clinical characteristics-concentration,concentration-response,and concentration-ADRs were analyzed.Results:A total of 30 patients were enrolled,comprising 13 males and 17 females,with a median age of 72(45-94)months.The median dose and concentration were 1.39(1.09-1.56)mg/kg and 2.70(2.25-4.13)mg/L,respectively.Of the enrolled patients,14 responded to treatment,whereas 16 did not.Additionally,five experienced adverse drug reactions.No linear correlation was observed between eltrombopag concentration and clinical characteristics.The concentration was lower in the response group than in the nonresponse group,but there was no significant difference(t=0.755,P=0.457).Patients who experienced ADRs had a higher concentration than those without ADRs(t=2.538,P=0.017).The area under the receiver operating characteristic curve of ADRs was 0.78(95%confidence interval:0.56-1.00).Youden’s index identified the cutoff point as 4.33 mg/L,with a sensitivity of 88%and a specificity of 60%.Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response.Interpretation:Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP.However,prolonged and high-dose administration may increase the likelihood of ADRs.Thus,examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.

General Anesthesia for Cesarean Section in a Pregnant Woman with Immune Thrombocytopenic Purpura (ITP): A Case Report and Review of the Literature

Background: Management of immune thrombocytopenia (ITP) during pre- gnancy can be challenging, particularly by identifying a threshold for safe administration of neuraxial/general anesthesia and minimizing postpartum hemorrhage. There is controversy over the safety of cesarean section (CS) in ITP patients. In this case report, we discuss general anesthesia management in a patient with ITP with severe thrombocytopenia. Case Presentation: A 28-year-old female with relapsed/refractory ITP and severe thrombocytopenia underwent general anesthesia and emergent cesarean section with successful outcomes and minimal bleeding. Platelet counts before CS were 5000 × 109 L, the patient received 1 unit of platelets before the procedure and 1 unit of platelet and tranexamic acid 500 mg was injected slowly during the procedure. No evidence of bleeding and no complications were observed in the patient or newborn. Conclusions: In an emergent circumstance, general anesthesia and cesarean section procedure were performed safely in a patient with severe thrombocytopenia, no hemorrhagic complications were seen for this patient or neonate. Objective of This Manuscript: To share our experience of a safe emergent CS procedure and general anesthesia in a patient with severe thrombocytopenia. Our experience may guide the management of ITP patients in emergent delivery circumstances.

Association between Immunological Thrombocytopenia and Thrombosis, Is It an Exotic Phenomenon?—A Case Report

Immunologic thrombocytopenia (ITP) is an autoimmune disease associated with the production of autoantibodies against specific platelet membrane glycoproteins. A thrombotic event as an unusual occurrence during ITP is becoming more and more frequent. In fact, several recent studies have shown an increased thrombotic risk in this situation. The case presented here is that of a fifty-one-year-old woman with extensive cerebral venous thrombosis 2 years after her ITP diagnosis. During IT, thrombosis may be triggered by the release of pro-thrombotic platelet micro-particles and by platelet activation due to the interaction between autoantibodies and platelet glycoproteins. Immunosuppressive therapy has also been linked in several studies to the thrombotic phenomenon. Increased thromboembolic risk should be taken into account in all ITP patients.

Diagnostic Approach of Thrombocytopenia in Pregnancy: A Review

Thrombocytopenia (defined as platelet count 9/L) is present in 7% - 12% of pregnant women at delivery. Although there are mild etiologies of this condition that are often diagnosed incidentally, there are more severe causes that can be life threating. Thrombocytopenia also has a great implication in surgical risk and regional anesthesia. A structured evaluation of thrombocytopenia is necessary to allow an adequate diagnostic approach. Here we summarized the current knowledge of thrombocytopenia in pregnancy.

MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages

Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of inflammation.Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.The expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were determined.Macrophage phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying mechanisms.The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment.The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages.Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of MST4.In a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of thrombocytopenia.Downregulation of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of macrophages.Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.

Combination of two target agonists of the thrombopoietin and thrombopoietin receptor in the treatment of elderly patients with refractory immune thrombocytopenia

Immune thrombocytopenia(ITP)is common in the elderly.Because of the coexistence of multiple diseases,there are many reservations regarding corticosteroid use in the elderly.Thrombopoietin(TPO)and its analogs can promote platelet production,but it is often difficult to correct TP in a short period.Recombinant human TPO(rh-TPO)acting on the cell membrane and the small-molecule TPO-receptor(MPL)agonist acting on the transmembrane receptor may have synergistic effects and accelerate platelet production because of different sites of action in the signaling pathway.In this study,two elderly patients with refractory ITP were successfully treated with two TPO-MPL signaling pathway agonists:recombinant human thrombopoietin(rh-TPO)and eltrombopag.This combination is safe with rapid and lasting effects.However,in elderly patients with refractory,recurrent,and glucocorticoid contraindications,the combination of different TPO agonists'clinical efficacy and adverse reactions needs to be further evaluated.

Effect of Yiqi Tongyang Decoction(益气通阳方) on Blood T Cell Subsets in Patients with Chronic Immune Thrombocytopenia

Objective： To measure the proportions of blood T cel subsets, Th1, Th2, Th17, Th22, and Treg cel s, and other parameters in patients with chronic immune thrombocytopenia（CITP） before and after treatment with Yiqi Tongyang Decoction（益气通阳方, YTD） to explore T cel status of patients with CITP, and to define the mechanism of action of YTD. Methods： The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cel s in 30 patients with CITP（22 females and 8 males） were analyzed using multiparametric flow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers（14 males and 12 females） acted as a control. T-box expressed in T-cel s（T-bet） and GATA binding protein 3（GATA-3） m RNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction. Results： The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy（P〈0.05）. Th1 cel numbers and the Th1/Th2 ratio fel in the treated patients with CITP to approximate the values of the control group（P〉0.05）. Th17 cel numbers and the Th17/Treg ratio also decreased in the treatment group（P〈0.05）, but not to the levels of the controls. The number of Treg cel s in the peripheral blood of patients with CITP before treatment was lower than that in the control group（P〈0.05）, but increased after YTD treatment（P〈0.05）, but not to the level of controls. T-bet and GATA-3 m RNA levels in peripheral blood were initially higher in patients before treatment than controls（P〈0.05）, but decreased after YTD therapy（P〈0.05）. Conclusions： Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cel s, play important roles in the pathogenesis of CITP. YTD efficiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.

Recombinant human thrombopoietin in combination with cyclosporin A as a novel therapy in corticosteroid-resistant primary immune thrombocytopenia

Background The management of patients with refractory immune thrombocytopenia （ITP） is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin （rhTPO） in combination with cyclosporin A （CsA） for the management of patients with corticosteroid-resistant primary ITP.

Hematologic manifestations of Helicobacter pylori infection

Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.

Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders.Here,we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia(ITP)patients and 52 healthy controls.Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally,and classifier based on species markers distinguished individuals with ITP from healthy controls.In particular,the abundance of Ruminococcus gnavus,Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-na?ve ITP patients,and the alterations of microbial species were correlated with clinical indices.Functionally,the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP,which may contribute to the onset of ITP by affecting the immune system.Furthermore,we found that corticosteroid treatment affected the gut microbiome of ITP.Compared with corticosteroid-sensitive ITP patients,we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome,which was different from that of the treatment-na?ve ITP patients.Together,we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.