The immune haemolytic anaemias: a century of exciting progress in understanding

Dacie, Sir John

doi:10.1046/j.1365-2141.2001.02945.x

Cited by 50 publications

(26 citation statements)

References 150 publications

(128 reference statements)

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“…Several overview articles have reviewed the pathogenesis, clinical features, and prognosis of AIHA in the past [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In the current article, we attempted to summarize previous and current knowledge on AIHA with special reference to triggering factors, the pathogenesis of the disease, clinical symptoms and features, established treatment options as well as emerging new therapeutic approaches.…”

Section: Introductionmentioning

confidence: 98%

Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review

Valent

Lechner

2008

Wien Klin Wochenschr

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Autoimmune haemolytic anaemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red cells. The disorder may be a primary (idiopathic) or a secondary disease. The diagnosis is based on the presence of anaemia, signs of haemolysis with reticulocytosis, low haptoglobin, increased lactate dehydrogenase, elevated indirect bilirubin, and a positive direct antiglobulin test (Coombs test). Sometimes, not all of these typical features are present. Most AIHA are caused by warm antibodies, whereas cold antibodies are less commonly detected. While half of the warm antibody-based AIHA are idiopathic anaemias, almost all cold antibody AIHA are secondary anaemias. Underlying diseases are Non Hodgkin's lymphomas and systemic autoimmune disorders, and less frequently organ transplantation, infections, or solid tumors. Moreover, AIHA is an important complication of treatment with nucleoside analogs. Most patients with AIHA require therapy. In warm antibody AIHA, standard first line therapy are glucocorticosteroids with or without high dose immunoglobulins, whereas splenectomy is considered second-line therapy. Response rates of primary AIHA to corticosteroid therapy are high. After initial remission, the dose should be tapered down slowly and with caution, and in some cases, low-dose maintenance therapy is required. The efficacy of standard therapy is low in secondary AIHA that develops in lymphoma patients, posttransplant patients, or tumor patients. Among other immunosuppressive treatments, rituximab (anti-CD20) appears to be highly effective in patients with warm antibody AIHA refractory to standard therapy. Mycophenolate mofetil is quite effective in AIHA patients with an underlying autoimmune or lymphoproliferative disease. Patients with cold agglutinins are refractory to steroids and splenectomy. Half of these patients may respond to rituximab, although responses usually are short-lived. Sometimes, AIHA that is associated with malignant lymphomas or tumors, disappears after successful anti-lymphoma or anti-tumor therapy.

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Section: Introductionmentioning

confidence: 98%

Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review

Valent

Lechner

2008

Wien Klin Wochenschr

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“…Pathogenesis of AIHA involves two underlying mechanisms, viz , erythrophagocytosis of autoantibody-coated erythrocytes by macrophages in the reticulo-endothelial system in liver and spleen [6,7], and complement mediated lysis of erythrocytes following binding of IgM autoantibodies [8]. AIHA has been extensively investigated mainly for the understanding of its pathogenesis, clinical features and prognosis [3,6,9,10]. However the modulation of erythropoietic homeostasis and the turnover pattern of circulating erythrocytes are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse

2016

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Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA) in C57BL/6 mice after 5–6 weeks. Using the double in vivo biotinylation (DIB) technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS) were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline). Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA.

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“…[1][2][3][4][5] The incidence has been estimated to be 1/10 6 per year. 6,7 Anemia results from binding of monoclonal cold agglutinins, most often IgM with κ light chains, to the I antigen on the erythrocyte surface.…”

Section: Introductionmentioning

confidence: 99%

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nCAD diagnosed in the time period between 1995 and 2012 were studied. There were 36 women and 18 men with an age range of 40-92 (median 73) years. All patients had a clinical history of CAD with a variable degree of anemia, a positive C3d-specific direct antiglobulin test and a cold agglutinin titer in excess of 64. Monoclonal IgM had been detected in the serum of all patients by agarose electrophoresis and immunofixation. None of the patients had lymphadenopathy or splenomegaly. Clinical follow-up ranged from 3 to 152 months, with a median follow-up of 72 months. The study was approved by the institutional and regional ethical committees. Biopsy materialArchival hematoxylin and eosin-stained sections of bone marrow trephine biopsies from the 54 patients, obtained at diagnosis, were reviewed. Fourteen biopsies were fixed in 4% formaldehyde, 18 in Bplus fixative and 22 in B5 fixative. In addition, part of the diagnostic trephine biopsy of eight patients had been snap-frozen in liquid nitrogen. Two of the patients had undergone splenectomy in an attempt to reduce hemolysis. Hematoxylin and eosin-stained archival sections of formalin-fixed splenic tissue of these patients were reviewed. ImmunohistochemistryImmunohistochemical analysis was extended or repeated whenever archival sections were not available or of bad quality. The primary antibodies and the method used for immunohistochemical analysis of the bone marrow trephine biopsies are described in the Online Supplementary Methods. Flow cytometryFlow cytometry was performed on samples from 25 patients and included a total of 46 bone marrow and 10 paired peripheral blood samples, anticoagulated with heparin and EDTA, respectively. On samples analyzed before 2011, a four-color analysis 18 and from 2011 onwards, an eight-color analysis 19 was performed with antibody combinations as described in the Online Supplementary Methods.Immunoglobulin heavy chain gene sequencing, and BCL6 and MYD88 mutation analyses DNA was extracted from frozen bone marrow trephine samples, obtained from eight patients, using the EZ1 tissue kit (Qiagen, Hilden, Germany) and from formaldehyde-fixed paraffin embedded-tissue sections from another nine patients using the QIAamp DNA FFPE tissue kit (Qiagen). Immunoglobulin heavy chain gene analysis and BCL6 intron 1 mutation analysis was only performed on DNA from frozen tissue samples whereas MYD88 mutation analysis, requiring less intact DNA, was performed on frozen and formaldehyde-fixed tissue samples.BCL6 intron 1 was amplified using three sets of overlapping polymerase chain reaction (PCR) primers covering nucleotides 24 to 790 in GenBank sequence AF191831. The primer pairs and PCR conditions are described in the Online Supplementary Methods. PCR products were sequenced and analyzed using the BLAST database.The MYD88 L265P mutation (NM_002468) was analyzed using PCR and a SNaPshot multiplex kit (Applied Biosystems). PCR primers and conditions are described in the Online Supplementary Me...

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The immune haemolytic anaemias: a century of exciting progress in understanding

Cited by 50 publications

References 150 publications

Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review

Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review

Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

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