Development Of Autoimmune Hemolytic Anemia Research Articles

Mitigation of checkpoint inhibitor–induced autoimmune hemolytic anemia through modulation of purinergic signaling

AbstractImmune checkpoint inhibitors (ICPis) have revolutionized cancer immunotherapy but also can induce autoimmune hemolytic anemia (AIHA), a severe disease with high mortality. However, the cellular and molecular mechanism(s) of AIHA secondary to ICPi therapy (ICPi-AIHA) are unclear, other than being initiated through decreased checkpoint inhibition. Herein, we report ICPi-AIHA in a novel mouse model that shows similar characteristics of known human ICPi-AIHA (eg, autoantibodies, hemolysis, and increased mortality). During ICPi-AIHA, there is the simultaneous reduction of 2 regulatory T-cell populations (FoxP3+ and Tr1 [type 1 regulatory cells]) and an increase in inflammatory T helper cell 17 (TH17). Moreover, a novel CD39+CD73–FoxP3–CD25– CD4+ T-cell subset (ie, CD39 single positive [CD39SP]) emerges, and early increases in CD39SP predict AIHA development; CD39 is an ectonuclease that breaks down adenosine triphosphate (ATP). Additionally, we found that boosting ATPase activity by injecting recombinant apyrase mitigates AIHA development and significant CD39SP reductions, both suggesting a functional role for CD39 and demonstrating a novel therapeutic approach. Importantly, CD39SP are detectable in multiple mouse models developing AIHA and in patients with AIHA, demonstrating applicability to idiopathic and secondary AIHA. Highlighting broader autoimmunity relevance, ICPi-treated NZB mice experienced accelerated onset and severity of lupus, including AIHA. Moreover, ICPi treatment of healthy B6 animals led to detectable CD39SP and development of autoantibodies against multiple autoantigens including those on red blood cells and platelets. Together, our findings provide further insight into the cellular and molecular mechanisms of ICPi-AIHA, leading to novel diagnostic and therapeutic approaches with translational potential for use in humans being treated with ICPi.

Abstract B030: Intracerebral and intraventricular hemorrhage due to severe thrombocytopenia: A rare case of Evans syndrome

Abstract Introduction: Evans syndrome (ES) is a rare autoimmune disorder characterized by the development of autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and/or immune neutropenia (AIN) without an identifiable cause. It is believed to involve immune system dysregulation, leading to the destruction of red blood cells, platelets, and neutrophils. Case Presentation: A 68-year-old male with a history of coronary artery disease, hypertension, diabetes, and atrial fibrillation presented with abdominal pain and diarrhea. Laboratory tests revealed a platelet count of 3k, suggesting ITP. Initial treatment with dexamethasone and platelet transfusion provided limited improvement. A bone marrow biopsy showed mildly hypercellular bone marrow with trilineage hematopoiesis. However, the patient's condition rapidly deteriorated, and he returned to the emergency department with severe symptoms, including headache, gum bleeding, and lower extremity petechiae. A CT scan revealed a large intraparenchymal hematoma with intraventricular hemorrhage, highlighting the risk of life-threatening bleeding in ES patients. Discussion: The patient was managed with platelet transfusions, high-dose steroids, and intravenous immunoglobulin (IVIG), which provided temporary relief but failed to maintain stable platelet levels. Further investigations revealed a positive antinuclear antibody (ANA), suggesting an underlying rheumatological condition and confirming the diagnosis of secondary ES. This finding necessitated the exploration of treatment options. Of interest is Romiplostim (Promacta), a thrombopoietin receptor agonist, which has shown promise in increasing platelet counts and reducing bleeding episodes in refractory ITP. Considering the positive ANA and the suspected rheumatological etiology, Romiplostim may serve as a viable long-term treatment option to stabilize platelet levels and mitigate bleeding risks in this case. Conclusion: This case highlights the complexity of Evans syndrome and emphasizes the need to promptly recognize and manage life-threatening bleeding complications, particularly in older patients. The presence of a positive ANA suggests an underlying rheumatological condition, necessitating comprehensive evaluation, and tailored therapeutic approaches. Although further research is needed to understand the pathogenesis and optimal management strategies for ES, Romiplostim holds promise as a potential treatment for patients with secondary ES who are unresponsive to conventional therapies. Citation Format: Kiersten R. Patterson, Aliya M. Khan, Raj Patel. Intracerebral and intraventricular hemorrhage due to severe thrombocytopenia: A rare case of Evans syndrome [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B030.

A rare case of Evans syndrome presenting as retrobulbar neuritis

Evans syndrome (ES) is a rare disease characterized by simultaneous development of autoimmune hemolytic anemia and immune thrombocytopenia with or without immune neutropenia. We report the first case of ES presenting as retrobulbar neuritis. Purpose of this report is to create awareness about ES. A 25-year-old female presented with sudden painful loss of vision. Neuroimaging confirmed retrobulbar neuritis. She had menorrhagia and iron-deficiency anemia. She had pallor, hepatosplenomegaly, and hemolytic anemia. She was treated with intravenous steroids. ES is a disease of high morbidity.

A case of Evans syndrome

Evans syndrome is an autoimmune disorder described by Robert Evans in 1951 specifying that a link exists between primary thrombocytopenic purpura and acquired haemolytic anaemia. It is a rare autoimmune disorder characterised by the simultaneous or sequential development of autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Approximately, Evans syndrome represent 5-10% of warm autoimmune haemolytic anaemia cases and 2-5% of ITP cases. It is basically a diagnosis of exclusion. We present a 50-year-old female presented with anaemia, jaundice and petechia. Patient indirect bilirubin was raised, Coombs test was positive, lactate dehydrogenase and reticulocyte count were raised. Based on the Coombs positive haemolytic anaemia and thrombocytopenia patient was diagnosed with Evans syndrome. ANA profile was positive for SS-A suggestive of underlying autoimmune disorder. Evans syndrome is difficult to diagnose and treat. Typically, corticosteroids and other immunosuppressive medications are used to manage the syndrome.

Characterization of Inborn Errors of Immunity in Recurrent Autoimmune Cytopenias in Children: A Report from Central California Cohort

Abstract Autoimmune cytopenias are characterized by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and/or autoimmune neutropenia. Evans syndrome (ES) is a condition characterized by simultaneous or sequential development of AIHA and ITP and/or immune neutropenia. Inborn errors of immunity driven multilineage cytopenias including ES requires further characterization to identify therapeutic targets. We evaluated our cohort of children with immune cytopenias to characterize mutations in inborn disorders of immunity and response to targeted therapy. To this end, we retrospectively reviewed the medical records of children between the ages of 0-21 years who presented to our hematology clinic with recurrent immune cytopenia between the years of 2018-2021. Rheumatological diseases, lymphoproliferative disorders, bone marrow failure syndromes, infections, drugs, toxins and metabolic disorders were excluded in the study. Children presenting with isolated idiopathic thrombocytopenic purpura or neutropenia were also excluded from the study. We utilized lymphocyte immunophenotyping and next generation sequencing involving 474 known genes (Invitae: Test code-08100) causing primary immunodeficiency in our pediatric patients with recurrent AIHA or multilineage immune cytopenias. Of the 59 patients with AIHA and multilineage immune cytopenias, 18 (30.5%) had recurrence of cytopenias after initial diagnosis. The age ranged from 1-20 years and 33% (n=6) were of the female gender (Table 1). AIHA (n=5, 28 %) and ES (n=5, 28%) were the most common presentation in patients with recurrent cytopenias. Autoimmune pancytopenia (n=4, 22.2%) was another common presentation. One child progressed to autoimmune pancytopenia after being diagnosed with AIHA. Pathogenic mutations in inborn errors of immunity were identified in 38.8% of the children. No mutations or variants were identified in 5 children (28%). Majority of patients received immunomodulatory treatments (Table 2) which resulted in remission (n=12, 66.6%). Immune cytopenias associated with Di-George syndrome were responsive to sirolimus with both children attaining remission. There was a death in the cohort related to the underlying condition. In conclusion, inborn errors of immunity were identified in recurrent immune cytopenias. Targeted therapies helped to achieve durable remission in children with specific mutations. Larger studies are warranted to understand the long-term therapeutic response in these children. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development and exacerbation of autoimmune hemolytic anemia following COVID-19 vaccination: A systematic review.

Autoimmune hemolytic anemia (AIHA) is caused by the production of autoantibodies against RBCs. COVID-19 vaccines can reduce the risk of severe disease, however, various adverse effects such as AIHA were observed following vaccination. This review aimed to assess the relationship of AIHA and COVID-19 vaccination using the PRISMA guidelines. Among 18 cases included in this review, new post-vaccination AIHA development was reported in 11 patients (7 women and 4 men) with a median age of 67.0 years. In 7 of 11 and 3 of 11 cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 14 days, respectively. In 1 of 11 cases, the AIHA occurred on Day 17 after booster vaccination. Ten of 11 and 1 of 11 AIHA patients received mRNA- and vector-based vaccine, respectively. After vaccination, 9 of 11, 1 of 11, and 1 of 11 AIHA patients developed warm IgG, cold IgM, and mixed autoantibodies against RBCs, respectively. Significant AIHA exacerbation was reported in seven patients (four women and three men) with a median age of 73.0 years. In 4 of 7 and 2 of 7 exacerbated AIHA cases, the onset of symptoms occurred after first and second vaccine dose with median times of 7 and 3 days, respectively. In 1 of 7 exacerbated AIHA cases, the onset of symptoms was observed on Day 2 after booster vaccination. All exacerbated AIHA cases received mRNA-based vaccines; 3 of 7 and 4 of 7 exacerbated AIHA cases developed IgG and IgM against RBCs, respectively. This review provides a comprehensive explanation regarding the AIHA development and exacerbation after COVID-19 vaccination.

Risk factors for autoimmune hemolytic anemia in children with transfusion-dependent thalassemia at a tertiary referral hospital

Repeated transfusions of children with transfusion-dependent thalassemia (TDT) save their lives while causing complications such as the development of autoimmune hemolytic anemia (AIHA). Studies regarding this matter have not yet been extensively reviewed. Therefore, we aim to assess the risk factors of developing AIHA in children with TDT.

Late-onset refractory autoimmune hemolytic anemia following autologous hematologic recovery after allo-HSCT in aplastic anemia-PNH syndrome

A 31-year-old man underwent allogeneic bone marrow transplantation (BMT) for the treatment of transfusion-dependent aplastic anemia (AA) after conditioning with a regimen including fludarabine, cyclophosphamide, and antithymocyte globulin. The patient developed a late graft rejection on day 103 and showed autologous hematologic recovery not requiring transfusions on day 76. Peripheral blood leukocytes were of 100% recipient origin on day 103, and paroxysmal nocturnal hematuria (PNH)-type granulocytes were detected 5 months after BMT. The patient suddenly experienced hemolytic symptoms triggered by cold stimulation, and was diagnosed with autoimmune hemolytic anemia (AIHA) 37 months after BMT. Although anemia was ameliorated by prednisolone (PSL), hemolytic attacks repeatedly occurred, which became refractory to corticosteroids. Moreover, the patient underwent a splenectomy for the steroid-resistant AIHA and achieved AIHA remission without the need for PSL at 53 months after BMT. The immune tolerance breakdown to erythrocyte antigens was thought to have occurred due to various factors including immune AA, medication, cold stimulation, and infection, leading to AIHA development in this case.

COVID-19-associated Evans syndrome: A case report and review of the literature

Evans syndrome is a rare condition characterized by simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia (and/or immune neutropenia). Coronavirus disease 2019 (COVID-19) may cause various hematologic conditions, such as coagulation abnormalities (e.g., bleeding or thrombosis) or cell count alterations (e.g., lymphopenia and neutrophilia). COVID-19 may also induce Evans syndrome via immune mechanisms. Here, we describe the case of a patient developing Evans syndrome shortly after COVID-19 infection. Immune thrombocytopenia and warm-type autoimmune hemolytic anemia developed simultaneously, and intravenous immunoglobulin and methylprednisolone were initially administered. Additionally, we intend to review all COVID-19-induced Evans syndrome cases currently present in the literature and emphasize the differences as well as the similarities regarding patient characteristics, relationship to COVID-19 infection, and treatment approach. Since autoimmune cytopenias are frequent in COVID-19 patients, clinicians should pay particular attention to profound and abrupt-onset cytopenias. In these circumstances, hemolysis markers such as lactate dehydrogenase, haptoglobulin, Coombs tests, etc. should be investigated, and the possibility of Evans syndrome should always be considered to ensure prompt and appropriate treatment. These factors are essential to ensure hematologic recovery and prevent complications such as thrombosis.

Клінічний випадок вагітності, ускладненої гепариніндукованою тромбоцитопенією, у жінки з синдромом Еванса

The simultaneous development of autoimmune hemolytic anemia and immune thrombocytopenia is known as Evans syndrome. This pathology is extremely rare during pregnancy, requires careful differential diagnosis and is associated with a high risk of hemorrhagic and thromboembolic complications. Treatment approaches for autoimmune hemolytic anemia and immune thrombocytopenia are similar, but in the case of autoimmune hemolytic anemia, thromboprophylaxis is mandatory. Heparin-induced thrombocytopenia is a serious adverse event of anticoagulation. One presents with a decrease in platelets but a paradoxical increase in thrombotic risk and mandates switching of the anticoagulant agent to a non-heparin one. Clinical case. We describe the case of pregnancy complicated with Evans syndrome and development of heparin-induced thrombocytopenia at 28 weeks. Treatment of the underlying disease was effective on the use of first-line therapy. Fondaparinux and vitamin K antagonist (warfarin) have been used to treat heparin-induced thrombocytopenia. Monitoring of the fetal condition is carried out with careful control of Doppler ultrasound of the middle cerebral artery. Successful change of anticoagulant, close surveillance and carefully selected therapy allowed to achieve a successful termination of pregnancy. A healthy female newborn with body weight 2450 g, 8–8 Apgar scores was vaginally delivered uneventful at the 38th week. There were neither neonatal thrombocytopenia nor anemia. During the year after birth, the woman's condition is not worse, the child develops according to age. An analysis of similar cases of pregnancy from the literature is described. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: thrombocytopenia, hemolytic anemia, pregnancy, Evans syndrome, heparin-induced thrombocytopenia.

A RARE CASE REPORT OF EVANS SYNDROME IN PREGNANCY

The simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) is known as Evans syndrome,which is very rare in pregnancy.We experienced a case of Evans syndrome in pregnancy.A 23-year-old primigravida with 37 weeks of gestation presented to the labor room with Evans syndrome. Her blood reports revealed features of hemolysis with macrocytic anemia, thrombocytopenia, elevated LDH, and low serum haptoglobin levels, and a direct antiglobulin test (DAT) was positive. A healthy female newborn with 3200 g was delivered by cesarean section.After delivery, DAT remained positive, and her platelet count falls markedly, and bone marrow transplantation was done.When Evans syndrome diagnosed during pregnancy, close and careful observation is essential because it can worsen both the maternal and fetal condition.

A Rare Case of Simultaneous Evans Syndrome and Primary Antiphospholipid Syndrome

Evans Syndrome (ES) is a rare autoimmune disorder that presents with simultaneous or sequential development of autoimmune hemolytic anemia (AIHA), thrombocytopenia, and/or neutropenia. This disease may occur in conjunction with other autoimmune disorders. Primary antiphospholipid syndrome (APS) is a disorder characterized by thrombosis, which can cause life-threatening complications such as fetal demise, strokes, or deep vein thrombosis.A 67-year-old male with type 2 diabetes mellitus, hypertension, and renal insufficiency presented with concomitant ES and APS. His hematological abnormalities began in 2013 after a deep vein thrombosis of the left lower extremity led to a diagnosis of APS and was started on chronic warfarin. In 2014, he was found to have immune thrombocytopenia (ITP) with relapses the following year. Several months later, he was hospitalized and diagnosed with AIHA. In the setting of his previous episodes of ITP and current AIHA, the diagnosis of ES was made. The initial treatment was 100 mg prednisone taper, but rituximab was required to make complete platelet recovery.The severe deterioration and rapid recovery with proper treatment of the patient highlights the importance of a timely diagnosis of ES. Mild thrombocytopenia can be associated with APS; however; severe thrombocytopenia may warrant further investigation for other possible causes. Maintaining ES on the differential diagnosis of patients with APS and thrombocytopenia could enhance health outcomes.

PB1963 CHARACTERISTICS OF NEWLY DIAGNOSED AUTOIMMUNE HEMOLYTIC ANEMIA: 5‐YEARS OF SINGLE‐CENTER EXPERIENCE

Background:Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease in which red blood cells (RBC) are targeted by autoantibodies confirmed with positive direct antiglobulin test (DAT), resulting in premature destruction of RBC. AIHA may be subdivided into warm antibody AIHA (wAIHA) and cold antibody AIHA (cAIHA), and also to primary and secondary depending on the presence of an underlying disorder. In addition to that, patients may have positive DAT but without features of hemolysis, and some of them will later develop AIHA.Aims:The aim of this study was to analyze characteristics of newly diagnosed DAT positive AIHA patients during the 5 years period in our tertiary center, as well to assess DAT positive patients without features of AIHA.Methods:This was a single‐center retrospective cohort study performed at the University Hospital Center (UHC) Zagreb, Zagreb, Croatia, Department of Internal Medicine, Division of Hematology. We included data for all consecutive adult patients with a newly diagnosis of DAT positive AIHA between 2014 and 2018, and also all DAT positive patients without features of hemolysis in that time period. This study was approved by the UHC Ethical Committee. Descriptive statistics was performed and included means ± SD or median (range) as appropriate for continuous variables and frequency (percentage) for categorical variables.Results:The data from 56 patients (50% women) with newly diagnosed DAT positive AIHA during the study period were analyzed. The median age at time of AIHA diagnosis was 67 years (range 22–90 years). Majority of AIHA was wAIHA (51 (91.1%) patients). AIHA was considered primary in only 14 (25%) patients and was associated with an underlying disorder in 42 (75%) patients. The various disorders were associated with secondary wAIHA, the most frequently B‐cell lymphoproliferative malignant diseases (33%), solid tumors (9.8%), myelodisplastic syndrome (9.8%) and autoimmune diseases (9.8%). Median hemoglobin level at the AIHA diagnosis was 71 g/L. 82.1% of patients received RBC transfusion. Seven (12.5%) patients did not require immunosuppressive treatment and other received mostly corticosteroids as the 1st line of therapy. Rituximab received 9 patients (17.6%) with wAIHA, mostly as the 2nd line of treatment. Eight patients (14.3%) with AIHA developed thrombosis (7 with wAIHA and 1 with cAIHA). During the 5‐years study period additional 120 patients with DAT positive results but without signs of hemolysis were detected.Summary/Conclusion:Data from our 5‐years single centre experience with AIHA are comparable with literature data. Majority of patients had secondary AIHA and wAIHA. Rituximab is used mostly as the second‐line treatment and corticosteroid‐sparing agent for wAIHA. Significant number of patients with DAT positive results but without features of hemolysis was detected, and they need to be closely monitored for possible development of AIHA.

C5aR activation in the absence of C5a: A new disease mechanism of autoimmune hemolytic anemia in mice.

IgG Fc receptors (FcγRs) and the C5a anaphylatoxin receptor (C5aR) were identified as key regulators of type II autoimmune injury in mice. However, and with respect to C5aR, the relative importance of C5a for IgG autoantibody-induced cellular destruction remained unclear. Using an experimental model of autoimmune hemolytic anemia (AIHA), we here report marked differences in the development of AIHA between mice lacking C5aR and C5-deficient (Hc0 ) strain, indicating a limited role of C5 in this type of C5aR-regulated disease. Ex-vivo-analyses of liver homogenates from anemic Hc0 mice demonstrate C5a-independent C5aR activation, upregulation of FcγR expression and amplification of erythrophagocytosis by macrophages. As assessed by pharmacological inhibition studies, targeting of C5aR, but not of C5, is effective in treating experimental AIHA. Collectively, these results define a previously unrecognized disease mechanism of C5aR activation in AIHA that does not necessarily involve C5 and C5a.

Human Immunodeficiency Virus Infection Increases the Risk of Incident Autoimmune Hemolytic Anemia: A Population-Based Cohort Study in Taiwan.

Currently, the association between human immunodeficiency virus (HIV) infection and subsequent development of autoimmune hemolytic anemia (AIHA) remains unclear. This nationwide population-based cohort study aimed to determine the association between incident AIHA and HIV infection in Taiwan. During 2000-2012, we identified people aged ≧15 years living with HIV (PLWH) from the Taiwan Centers for Disease Control HIV Surveillance System. Individuals were considered to be infected with HIV on the basis of positive results of an HIV type 1 Western blot. Age- and sex-matched controls without HIV infection were selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed until 31 December 2012 and observed for occurrence of AIHA. Of 171468 subjects (19052 PLWH and 152416 controls), 30 (0.02%) had incident AIHA during a mean follow-up of 5.45 years, including 23 PLWH (0.12%) and 7 controls (0.01%). After adjustment for age, sex, and comorbidities, HIV infection was found to be an independent risk factor of incident AIHA (adjusted hazard ratio, 20.9; 95% confidence interval, 8.34-52.3). Moreover, PLWH who were receiving highly active antiretroviral therapy were more likely to develop AIHA than those who were not receiving these drugs (adjusted hazard ratio, 16.2; 95% confidence interval, 3.52-74.2). Our study suggests that HIV infection is an independent risk factor for incident AIHA.

Fatal pulmonary embolism following splenectomy in a patient with Evan\u2019s syndrome: case report and review of the literature

BackgroundEvans syndrome (ES) is a rare disease characterized by simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Splenectomy is one of the treatment options for disease refractory to medical therapy. Venous thromboembolism (VTE) following splenectomy for hematological diseases has an incidence of 10%.Case presentationHere we describe a case report of a young patient hospitalized with severe hemolytic anemia with Hgb 4.8 g/dl. He developed thrombocytopenia with platelet nadir of 52,000/mm3, thus formally diagnosed with ES. He failed standard medical therapy. He underwent splenectomy and had a fatal outcome. Autopsy confirmed the cause of death as pulmonary embolism (PE).ConclusionsThis case report and review of the literature highlight important aspects of the association between VTE, splenectomy, and hemolytic syndromes including the presence of thrombocytopenia. The burden of the disease is reviewed as well as various pathophysiologic mechanisms contributing to thromboembolic events in these patients and current perioperative prophylactic anticoagulation strategies. Despite an advancing body of literature increasing awareness of VTE following splenectomy, morbidity and mortality remains high. Identifying high risk individuals for thromboembolic complications from splenectomy remains a challenge. There are no consensus guidelines for proper perioperative and post-operative anti-coagulation. We encourage future research to determine which factors might be playing a role in increasing the risk for VTE in real time with hope of forming a consensus to guide management.

Evans syndrome in infants

Abstract Background Evans’ syndrome is characterized by the reduction of at least two blood cell lines in the absence of other diagnoses; it was previously described as the simultaneous or sequential development of autoimmune hemolytic anemia and immune thrombocytopenia with unknown etiology. Incidence of 37% and mortality rate of 10% have been reported for Evans’ syndrome. Clinical cases We report the clinical presentation and evolution of Evans’ syndrome in two infants who were initially diagnosed with immune thrombocytopenia. The clinical diagnosis was supported by complementary studies and hematological disorders were corroborated. Both cases received treatment with steroids and intravenous immunoglobulin. Conclusions Other cell line disorders must be looked for when approaching children with thrombocytopenia. In the present cases, we found autoimmune hemolytic anemia and monocytosis. Therefore, infectious and immunological studies must be included. The treatment of choice are steroids, and intravenous immunoglobulin should be considered if severe immune thrombocytopenia is associated, as observed in these cases.

Evan's syndrome - a rare case report

Evan's syndrome is the coexistence of simultaneous or sequential development of Autoimmune Haemolytic Anaemia (AIHA) and Idiopathic Thrombocytopenia Purpura (ITP), with no known underlying etiology. The typical clinical course is chronic and relapsing, and therapy is generally progressive and poor. The etiology of Evans syndrome is unknown. Noncrossreacting autoantibodies are directed against antigens specific to red cells, platelets, or neutrophils. Evan's syndrome is an uncommon but not rare condition; its exact frequency is unknown. We report a case of Evan's syndrome which was admitted in our hospital.

IL-33 reflects dynamics of disease activity in patients with autoimmune hemolytic anemia by regulating autoantibody production.

Background Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment.Methods Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs.ResultsSerum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity.ConclusionsIL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0745-0) contains supplementary material, which is available to authorized users.

Molecular mechanisms of autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is an acquired immunological disease in which red blood cells (RBCs) are selectively attacked and destroyed (hemolyzed) by autoantibodies produced by the patient's own immune system. Several hypotheses regarding the mechanisms underlying the development of AIHA have been proposed, but the actual pathogenesis remains unclear. Since the major autoantigens in warm AIHA were determined to be Rh protein, band 3 and glycophorin A in 1993, helper T cells (Th1, Th2 and Th17) and regulatory T (Treg) cells specifically reacting to Rh peptides were reported in patients with AIHA. Recently, Th1 responses were found to be suppressed with synthetic peptides that are recognized by the Treg cells, and Th17 cells and interleukin 17 were shown to contribute to the induction and the development of AIHA. This approach to understanding AIHA pathogenesis may provide clues to finding novel targets for immunotherapy against AIHA.