Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.613
Filtrar
1.
J Allergy Clin Immunol ; 146(5): 1194-1200.e1, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32853638

RESUMO

BACKGROUND: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection. OBJECTIVES: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. METHODS: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs. RESULTS: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children. CONCLUSIONS: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Trombocitopenia/imunologia , Trombocitopenia/virologia , Adolescente , Anemia Hemolítica Autoimune/genética , Betacoronavirus , Pré-Escolar , Infecções por Coronavirus/imunologia , Haploinsuficiência , Humanos , Masculino , Mutação , Pandemias , Pneumonia Viral/imunologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Trombocitopenia/genética
2.
J Stroke Cerebrovasc Dis ; 29(8): 104924, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689602

RESUMO

Dabigatran is an orally active direct thrombin inhibitor, initially approved by FDA for the prophylaxis of stroke and systemic embolism in the setting of non-valvular atrial fibrillation (NVAF). Major bleeding is its most common adverse event which is of great concern. However, other types of adverse events such as esophagitis, esophageal ulcer, exanthem and pustular eruptions were reported increasingly in recent years. We present a case of immune hemolytic anemia (IHA) due to dabigatran use in a 72-year-old male with NVAF. This new and rare reported type of adverse event associated with dabigatran suggests that dabigatran may be a new cause of drug-induced immune hemolytic anemia (DIIHI).


Assuntos
Anemia Hemolítica Autoimune/induzido quimicamente , Antitrombinas/efeitos adversos , Dabigatrana/efeitos adversos , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/imunologia , Antitrombinas/administração & dosagem , Doença Crônica , Dabigatrana/administração & dosagem , Progressão da Doença , Substituição de Medicamentos , Glucocorticoides/administração & dosagem , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Resultado do Tratamento , Varfarina/administração & dosagem
5.
J Immunother Cancer ; 8(1)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32169870

RESUMO

BACKGROUND: The combination of the immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab is a mainstay of treatment for selected patients with metastatic melanoma. This combination also results in more frequent immune-related adverse events (irAEs) than either ICI alone. These irAEs can be severe and their pathogenesis is poorly understood. CASE PRESENTATION: We report a case of a woman with metastatic melanoma, treated with combined ipilimumab and nivolumab, who developed severe anaemia. While initial workup revealed autoimmune haemolytic anaemia, the anaemia persisted despite corticosteroids and paradoxical reticulocytopenia was observed. Bone marrow biopsy demonstrated a CD8+ T cell-mediated destruction of the red cell precursors implying concurrent pure red cell aplasia. Both processes resolved after the addition of cyclosporine A. CONCLUSIONS: This report describes a rare case of two concurrent mechanisms of haematological irAE in a patient treated with combined ICI therapy. Successful treatment resulted only after the second underlying mechanism of toxicity was uncovered. Prompt recognition of these unusual presentations of rare irAEs is now key to effective irAE management.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma/tratamento farmacológico , Adulto , Anemia Hemolítica Autoimune/induzido quimicamente , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/patologia , Antifúngicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclosporina/administração & dosagem , Feminino , Humanos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Melanoma/imunologia , Melanoma/patologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Prognóstico
6.
Medicine (Baltimore) ; 99(3): e18856, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011506

RESUMO

RATIONALE: Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune disorders. However, the concurrence of PBC and Sjögren syndrome (SS) with the subsequent onset of autoimmune hemolytic anemia (AIHA) is extremely rare. PATIENT CONCERNS: This study investigated a 60-year-old woman admitted to our hospital with complaints of xerostomia for 5 years, pruritus for 3 years, and abnormal liver function for 3 months. DIAGNOSES: The patient was suffering from typical clinical PBC and SS, and developed decompensated liver cirrhosis after 32 months of ursodeoxycholic acid (UDCA) therapy. In May 2018, she was readmitted to the hospital with a high fever of 39 °C, coughing, and sever fatigue without remission after 3 days of cephalosporin antibiotic therapy. During the clinical course of PBC, her antimitochondrial antibodies (AMA) titers fluctuated from 1:1000 to negative and then to weakly positive, determined by indirect immunofluorescence (IIF), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) based on recombinant mitochondrial antigens; furthermore, her titers of anti-gp210, an antinuclear antibody (ANA), increased sharply. Laboratory tests and imaging were performed to diagnose PBC and SS in September 2015. However, she was subsequently diagnosed with AIHA after 32 months of UDCA therapy based on the identification of pancytopenia, increased reticulocyte (RET) count, and a positive result from the direct Coombs test. INTERVENTIONS: UDCA, hepatic protectant, albumin infusion, chest drainage, rational antibiotic use, diuretics, and methylprednisolone were used to treat the patient. OUTCOMES: Liver cirrhosis was complicated by the development of AIHA, which became severe at 42 months of follow-up. LESSONS: This is the first case report showing a patient with comorbid PBC and SS, as well as the sequential development of AIHA with decreased AMA and increased anti-gp210 titers; this may have been due to immunodeficiency. These findings stress the importance of the serological screening of ANA profile, as well as repeated measurement of ANA and AMA to track PBC progression and prognosis.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/imunologia , Colangite/imunologia , Mitocôndrias/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Síndrome de Sjogren/imunologia , Anemia Hemolítica Autoimune/terapia , Autoanticorpos/sangue , Colangite/terapia , Terapia Combinada , Feminino , Humanos , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/terapia , Testes de Função Hepática , Pessoa de Meia-Idade , Complexo de Proteínas Formadoras de Poros Nucleares/sangue , Síndrome de Sjogren/terapia
8.
Sci Rep ; 9(1): 19716, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873137

RESUMO

Autoimmune haemolytic anaemia (AIHA) is a kind of autoimmune diseases characterized by autoantibodies which produced and secreted by abnormal activated B lymphocytes directed against red blood cells (RBC). Study reveals that about 50% AIHA mainly occurs secondary to lymphoproliferative disorders (LPD) and autoimmune diseases. In this study, we aim to explore the characteristics of patients with AIHA secondary to LPD. Fifteen patients with AIHA secondary to LPD (secondary group) and 60 with primary AIHA (primary group) were retrospectively included. Patients in the secondary group [(59.40 ± 4.74) y] were older than those in the primary group [(47.53 ± 2.30) y] (p = 0.024). Reticulocyte counts were lower for the secondary group [(134.55 ± 20.67) × 109/L] than for the primary group [(193.88 ± 27.32) × 109/L] (p = 0.09). Haptoglobin was higher in the secondary (0.75 ± 0.19) g/L than in the primary group (0.34 ± 0.05) g/L (p = 0.004). The ratio of CD3+CD4+/CD3+CD8+ was higher in the secondary (1.81 ± 0.41) than in the primary (1.05 ± 0.12) group (p = 0.025). Duration of remission was shorter in the secondary [(23.52 ± 5.20) months] than in the primary [(40.87 ± 3.92) months] group (p = 0.013). Relapse rate was higher for the secondary (33.3%) than for the primary (8.3%) group (p = 0.003). Mortality rate was higher in the secondary (33.3%) than in the primary (8.3%) group (p = 0.003). Progression-free survival was shorter in the secondary than in the primary group (p = 0.021). In conclusion, patients with AIHA secondary to LPD showed higher age at diagnosis, shorter remission time, and higher recurrence and mortality rates than did those with primary AIHA.


Assuntos
Anemia Hemolítica Autoimune/etiologia , Transtornos Linfoproliferativos/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/imunologia , Teste de Coombs , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Sci Rep ; 9(1): 19767, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875006

RESUMO

Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease mediated by antibodies against the patient's red blood cells. However, the underlying mechanisms for antibody production are not fully understood. Previous studies of etiology and pathogenesis of AIHA mainly focus on autoreactive B cells that have escaped tolerance mechanisms. Few studies have reported the function of TFH and TFR cells in the process of AIHA. The present study aimed to explore the potential mechanism of TFH and TFR cells in the pathogenesis of AIHA. With the model of murine AIHA, increased ratios of TFH:TFR, elevated serum IL-21 and IL-6 levels, and upregulated Bcl-6 and c-Maf expression were reported. Also, adoptive transfer of purified CD4+CXCR5+CD25- T cells from immunized mice promoted the induction of autoantibody in the AIHA mouse model. Altogether, our data demonstrate the important role of TFH cells for control and induction of AIHA. In the light of the key contributions of TFH cells to the immune response in AIHA, strategies aimed at inhibiting the TFH development or function should be emphasized.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Linfócitos T Reguladores/imunologia , Anemia Hemolítica Autoimune/patologia , Animais , Autoanticorpos/imunologia , Modelos Animais de Doenças , Centro Germinativo/patologia , Interleucina-6/imunologia , Interleucinas/imunologia , Camundongos , Proteínas Proto-Oncogênicas c-bcl-6/imunologia , Proteínas Proto-Oncogênicas c-maf/imunologia , Linfócitos T Reguladores/patologia
10.
J Coll Physicians Surg Pak ; 29(12): S106-S108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779758

RESUMO

Celiac disease (CD) is an autoimmune disorder with high incidence of multi organ involvement; especially, gastrointestinal manifestations and an increased risk of malignancies. Here we report a case of CD with celiac hepatitis, autoimmune hemolytic anemia (AIHA) and Grave's disease (GD) with their complications. Polyautoimmunity requires comprehensive analysis. While CD and GD were previously diagnosed, AIHA and cirrhosis were diagnosed during admission upon extensive work-up. Similarly, other autoimmune etiologies, such as autoimmune hepatitis (AIH), and/or primary biliary cholangitis were ruled out. All three diseases were treated afresh with strict adherence to a gluten-free diet (GFD) and carbimazole along with addition of medications for cirrhosis complicated by ascites. This was a rare case where non-adherence to a GFD led to such severe adverse events. A case of celiac hepatitis presenting with such a wide array of signs and symptoms has rarely been reported in the literature and the management of this patient was unique and challenging.


Assuntos
Anemia Hemolítica Autoimune/complicações , Autoimunidade , Carbimazol/uso terapêutico , Doença Celíaca/complicações , Dieta Livre de Glúten/métodos , Doença de Graves/complicações , Hepatite Autoimune/complicações , Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/terapia , Antitireóideos/uso terapêutico , Biópsia , Doença Celíaca/imunologia , Doença Celíaca/terapia , Feminino , Doença de Graves/imunologia , Doença de Graves/terapia , Hepatite Autoimune/imunologia , Hepatite Autoimune/terapia , Humanos , Adulto Jovem
11.
Rev Port Cir Cardiotorac Vasc ; 26(3): 223-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734976

RESUMO

Cold agglutinins (CA) are autoantibodies whose clinical significance depends upon titer and thermal amplitude. Patients, which undergo cardio-pulmonary bypass and especially hypothermic cardioplegia myocardial protection, represent a challenge regarding operative management, as tissue temperature should be maintained above the threshold of agglutination. We report on a case in which the presence of CA was discovered during elective aortic valve replacement surgery, and managed with normothermic cardiopulmonary bypass and continuous retrograde warm blood cardioplegia administration.


Assuntos
Anemia Hemolítica Autoimune/complicações , Ponte Cardiopulmonar/métodos , Parada Cardíaca Induzida/métodos , Doenças das Valvas Cardíacas/cirurgia , Hipotermia Induzida/efeitos adversos , Anemia Hemolítica Autoimune/imunologia , Valva Aórtica/cirurgia , Autoanticorpos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Crioglobulinas/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Parada Cardíaca Induzida/efeitos adversos , Doenças das Valvas Cardíacas/complicações , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos
13.
Vaccine ; 37(44): 6682-6687, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31562002

RESUMO

Cold agglutinin disease (CAD) is a rare, potentially life-threatening acquired autoimmune hemolytic anemia characterized by hemagglutination and hemolysis due to immunoglobulin-mediated (usually IgMκ) classic complement pathway activation. Complement inhibition (CI) represents a novel treatment option to control hemolysis. Due to CI patients (pts) are susceptible to encapsulated bacteria e.g. N. meningitidis. Therefore, meningococcal vaccination on CI is mandatory. In this study serologic response to the tetravalent conjugate vaccine Menveo® was analyzed in CAD pts on eculizumab treatment (DECADE trial) using rabbit serum as complement source (rSBA). Protective rSBA titers varied for meningococcal serogroups and over time reflecting an early decline to even non-protective rSBA titers. These data highlight the importance of serologic analyses under chronic CI. Currently, re-vaccination with a tetravalent meningococcal conjugate vaccine every 3 years is recommended on chronic CI. However, re-vaccination on CI might further rely on serologic analyses, implying even early booster vaccinations similar to adults with (functional) asplenia.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Proteínas do Sistema Complemento/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/sangue , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coelhos , Testes Sorológicos
14.
Hematology ; 24(1): 588-595, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392938

RESUMO

Objective: To explore the activity of B subsets from Autoimmune Hemolytic Anemia/Evans syndrome (AIHA/ES) patients. Methods: The expression of Bruton's tyrosine kinase (BTK) and phosphorylated BTK (p-BTK) on CD5+CD19+B and CD5-CD19+B lymphocytes were detected using flow cytometry in AIHA/ES patients with different disease states, healthy controls (HCs) and chronic lymphocytic leukemia (CLL) patients. The correlations of expressed BTK and p-BTK with clinical variables were analyzed. Results: Thirty six AIHA/ES patients (16 hemolytic, 20 remission), 11 CLL patients, and 15 HCs were enrolled. The expression levels of BTK and p-BTK on CD5+B lymphocytes in AIHA/ES patients were higher than those in HCs and CLL patients. The latter two groups had no significant difference, and were positively correlated with the quantity of IgE. The ratio of p-BTK to BTK on CD5+B lymphocytes of the hemolytic and remission groups was obviously higher than that on CD5-B lymphocytes (74.62 ± 6.42% and 29.63 ± 10.19%, respectively; P = 0.001 versus 77.95 ± 9.57% and 26.29 ± 6.86%, respectively; P = 0.006). The ratio of p-BTK to BTK on CD5+B lymphocytes (54.89 ± 9.56%) and CD5-B lymphocytes (30.86 ± 12.47%) did not differ significantly in HCs (P = 0.109). BTK did not differ significantly between CD5+ and CD5-B lymphocytes in AIHA/ES, but p-BTK on CD5+B lymphocytes was significantly higher than that on CD5-B lymphocytes in AIHA/ES patients. Conclusions: CD5+B lymphocytes are the major B subtype that is activated in AIHA/ES patients and it positively correlates with IgE.


Assuntos
Tirosina Quinase da Agamaglobulinemia/metabolismo , Anemia Hemolítica Autoimune/imunologia , Linfócitos B/metabolismo , Trombocitopenia/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Transfus Apher Sci ; 58(5): 693-696, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326291

RESUMO

BACKGROUND: In idiopathic autoimmune haemolytic anaemia (AIHA haemolytic antibodies are directed to every type of red cellsWestern blot studies have shown antibody positivity towards red cell anion channel complex which also includes band 4.2 a protein with similarities to tissue trans glutaminase. OBJECTIVE: Evaluation of AIHA for anti tissue transglutaminase antibody (Anti tTG). MATERIALS & METHODS: Twenty three AIHA patients were tested along with routine hamatogical work up, for a series of auto antibodies and red cell eluates and serum from the patents were tested against solubilised group O red cell ghosts on western blot. Other ancillary investigations were done to rule out complications and secondary causes of haemolysis. RESULTS: 11/23 patients (48%) were positive for anti tTG, Four, 3 and 8,7 patients were positive for anti thyroid, anti b2 glycoprotein, lupus anticoagulant and ANA respectively. One patient with anti tTG had biopsy proven celiac disease. Three patient developed DVT and all of them were lupus anticoagulant as well as b2 gp-1 antibody positive.17 had become Coombs test negative on treatment while 21/23 had positive western blot test. DISCUSSION & CONCLUSION: There is strong association of anti tTG antibody with idiopathic AIHA. Aetiological association of this finding needs exploration.


Assuntos
Anemia Hemolítica Autoimune , Proteínas de Ligação ao GTP , Transglutaminases , Adulto , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Imunofluorescência , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Transglutaminases/imunologia , Transglutaminases/metabolismo
17.
Transfus Clin Biol ; 26(3): 152-154, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277985

RESUMO

The complement is a key player of the innate immune response. It provides defense mechanisms that are not specific, but very efficient at neutralizing any invader, accounting for 4% of the proteins in the peripheral blood. Nevertheless, there is a dark side to the complement system, as it may activate its machinery against healthy cells such as peripheral blood red blood cells and platelets resulting in undesired hemolysis and thrombocytopenia, respectively. Understanding and identifying the role of complement in these settings allow physicians to adjust their diagnostic and therapeutic modalities accordingly. The role of complement in the pathophysiology and management of autoimmune hemolytic anemia and of alloimmune-mediated thrombocytopenia is under investigation and discussed.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Proteínas do Sistema Complemento/imunologia , Imunidade Inata/imunologia , Transfusão de Plaquetas , Anemia Hemolítica Autoimune/terapia , Especificidade de Anticorpos , Antígenos de Plaquetas Humanas/imunologia , Soro Antilinfocitário/sangue , Soro Antilinfocitário/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia
18.
Blood Adv ; 3(12): 1897-1906, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31235526

RESUMO

The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with <10 cases. Of 1371 articles retrieved, 1209 were excluded based on titles and abstracts. Two authors independently reviewed 10% and 16% of abstracts and full papers, respectively. After full-paper review, 84 studies were included. AIHA was most frequently (32 [52%] of 61) defined as hemolytic anemia with positive direct antiglobulin test (DAT) and exclusion of alternatives, but 10 of 32 also recognized DAT-negative AIHA. A lower threshold for diagnosis of DAT-negative AIHA was observed in literature on chronic lymphocytic leukemia. Definitions of anemia, hemolysis, and exclusion criteria showed substantial variation. Definitions of primary/secondary cold agglutinin disease/syndrome were not consistent. Forty-three studies provided criteria for treatment response, and other than studies from 1 center, these were almost entirely unique. Other criteria were rarely defined. Only 7, 0, 3, 2, 2, and 3 studies offered definitions of warm AIHA, paroxysmal cold hemoglobinuria, mixed AIHA, AIHA severity, disease phase, and refractory AIHA, respectively. Marked heterogeneity in the time period sampled indicates the need to standardize AIHA terminology.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/imunologia , Hemoglobinúria Paroxística/diagnóstico , Hemólise/fisiologia , Anemia Hemolítica Autoimune/terapia , Teste de Coombs/métodos , Eritrócitos/metabolismo , Hemoglobinúria Paroxística/etiologia , Humanos , Imunoglobulina G/efeitos dos fármacos , Imunoglobulina G/imunologia , Publicações/normas , Publicações/estatística & dados numéricos , Índice de Gravidade de Doença , Terminologia como Assunto
19.
Blood ; 134(1): 9-21, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30940614

RESUMO

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.


Assuntos
Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Adulto Jovem
20.
Autoimmunity ; 52(1): 12-20, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30784322

RESUMO

OBJECTIVE: To investigate the quantity and secretion function of cytokines-secreted CD5+ B lymphocytes in Autoimmune Haemolytic Anaemia (AIHA)/Evans syndrome (ES) patients. METHODS: Twenty-five untreated AIHA/ES patients, 28 remission AIHA/ES patients and 25 healthy controls (HCs) were enrolled in this study. The quantity of CD5+B lymphocytes which produce interleukin-10 (IL-10) (CD5+IL-10+) and transforming growth factor (TGF-ß1) (CD5+TGF-ß1+) were detected by flow cytometry (FCM). CD5+ B lymphocytes were sorted from peripheral blood (PB) by FCM and the expression of IL-10 and TGF-ß1 mRNA in CD5+ B cells were measured by real-time PCR (RT-PCR). RESULTS: The percentage of CD5+IL-10+B cells in CD5+ B lymphocytes in newly diagnosed patients was 82.18 ± 14.78%, which being significantly higher than that of remission AIHA/ES patients (56.68 ± 24.39%) and HCs (51.90 ± 22.95%) (p < .05). The percentage of CD5+IL-10+ B cells in CD5+ B lymphocytes in newly diagnosed patients was negatively correlated with haemoglobin (Hb), complement 3 (C3) (p < .05) and positively correlated with lactate dehydrogenase (LDH), total bilirubin (TBIL) and indirect unconjugated bilirubin (IBIL) (p < .05). The expression level of IL-10 mRNA in CD5+ B lymphocytes of newly diagnosed patients (49.34 ± 22.84) was higher than that of remission patients (3.97 ± 3.83) and HCs (1.78 ± 1.66) (p < .05). There was no significant difference among three groups with the proportion of CD5+TGF-ß1+ B lymphocytes and the expression level of TGF-ß1 mRNA in CD5+B lymphocytes (p > .05). CONCLUSIONS: CD5+ B lymphocytes could secrete IL-10 rather than TGF- ß1 which control the immune response in AIHA/ES.


Assuntos
Anemia Hemolítica Autoimune , Linfócitos B , Antígenos CD5 , Citometria de Fluxo , Interleucina-10 , Trombocitopenia , Fator de Crescimento Transformador beta1 , Adolescente , Adulto , Idoso , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígenos CD5/sangue , Antígenos CD5/imunologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/imunologia , Masculino , Pessoa de Meia-Idade , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...