Association of Graves' disease with Evans' syndrome in a patient with IgA nephropathy.
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A 20-year-old woman with IgA nephropathy was admitted to Jikei University Hospital for the treatment of rapid deterioration of renal function after receiving 131I-therapy against hyperthyroidism on October 23,1999, and hemodialysis was started. On admission, she was diagnosed as having Evans' syndrome in addition to known Graves' disease. Renal biopsy revealed end-stage renal damage, then, hemodialysis was maintained. Treatment for Evans' syndrome was also started and her general condition gradually improved. The present case implied that "Graves' disease" and "Evans' syndrome" could represent some of the manifestations of an underlying immunological disorder in the patient. (+info)
Myelodysplastic syndrome accompanied by Addison's disease and multiple autoimmune phenomena: steroid therapy resolved cytopenias and all immune disorders.
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We report here a patient with myelodysplastic syndromes (MDS), which was complicated with several autoimmune disorders and asymptomatic immunologic abnormalities. An 82-year-old woman with refractory anemia (RA) rapidly developed thrombocytopenia with the appearance of symptoms such as purpura, fatigue, anorexia, and weight loss. Furthermore, clinical examinations revealed that she also had Addison's disease, rheumatoid arthritis, and autoimmune hematological diseases such as thrombocytopenia and hemolytic anemia. However, the cytopenia and all autoimmune disorders were remarkably improved after she received steroid therapy. (+info)
Temporal differences in membrane loss lead to distinct reticulocyte features in hereditary spherocytosis and in immune hemolytic anemia.
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Spherocytic red cells with reduced membrane surface area are a feature of hereditary spherocytosis (HS) and some forms of autoimmune hemolytic anemia (AIHA). It is generally assumed that membrane loss in spherocytic red cells occurs during their sojourn in circulation. The structural basis for membrane loss in HS is improper assembly of membrane proteins, whereas in AIHA it is due to partial phagocytosis of circulating red cells by macrophages. A hypothesis was formed that these different mechanisms should lead to temporal differences in surface area loss during red cell genesis and during sojourn in circulation in these 2 spherocytic syndromes. It was proposed that cell surface loss could begin at the reticulocyte stage in HS, whereas surface area loss in AIHA involves only circulating mature red cells. The validity of this hypothesis was established by documenting differences in cellular features of reticulocytes in HS and AIHA. Using a novel technique to quantitate cell surface area, the decreased membrane surface area of both reticulocytes and mature red cells in HS compared with normal cells was documented. In contrast, in AIHA only mature red cells but not reticulocytes exhibited decreased membrane surface area. These data imply that surface area loss in HS, but not in AIHA, is already present at the circulating reticulocyte stage. These findings imply that loss of cell surface area is an early event during genesis of HS red cells and challenge the existing concepts that surface area loss in HS occurs predominantly during the sojourn of mature red cells in circulation. (+info)
Subclasses of warm autoantibody IgG in patients with autoimmune hemolytic anemia and their clinical implications.
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OBJECTIVE: To explore the mechanism of autoimmune hemolysis and establish a more sensitive test for autoimmune hemolytic anemia (AIHA). METHODS: IgG subclasses were tested in 40 patients with idiopathic or secondary AIHA by Coombs test with monoclonal antibodies. Hb, TBil, RC and FHb, as hemolytic parameters, were used to analyze the clinical implications of subclasses of AIHA warm autoantibody IgG. RESULTS: In most patients IgG incomplete warm autoantibody was IgG1 (27 patients), but IgG3 (20 patients), rarely IgG2 (14 patients) and IgG4 (9 patients) also occurred. Three groups were analyzed: Group A included 20 patients with IgG3; Group B included 14 patients with IgG1 bit without IgG3; Group C included 6 patients without IgG1 and IgG3. There were significant differences (P < 0.01) between groups in Hb, TBil, RC and FHb. Moreover, we also found that the sensitivity of Coombs test with polyclonal antiserums was 90.0%, while that of Coombs test with monoclonal antibodies was 97.5%. The effect of treatment was worst in patients with positive IgG3 autoantibody, whose hemolysis recurred frequently. CONCLUSION: IgG3 autoantibody was the most effective in bringing about red cell destruction, IgG1 autoantibody was less effective, IgG2 even less, whereas IgG4 autoantibody was shown to hardly affect red cell survival. Coombs test with monoclonal antibodies was more sensitive than that with polyclonal antiserums. Patients' respondence to treatment correlated with the type of IgG subclasses. (+info)
Remission of severe, intractable autoimmune haemolytic anaemia following matched unrelated donor transplantation.
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Immune-mediated haemolytic anaemia presenting post allogeneic bone marrow transplantation is often alloimmune in origin due to ABO or minor red cell incompatibilities. Autoimmune haemolytic anaemia is also recognised, is frequently difficult to treat and overall prognosis is often poor, usually from associated problems. Here, we present a case report of autoimmune haemolysis presenting in an 8-year-old boy 6 months post allogeneic bone marrow transplant requiring 4 years of immunosuppressive therapy before remission of haemolysis. This case report highlights the fact that it is possible for haemolysis to resolve post transplant even after years of immunosuppressive therapy. (+info)
Allogeneic stem cell transplantation for Evans syndrome.
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Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities. (+info)
B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia.
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BACKGROUND AND OBJECTIVES: Rituximab reacts specifically with the CD20 antigen and induces B-cell depletion. This could interfere with the production of autoantibodies in some immune diseases. The objective of this study was to assess the effects of rituximab in autoimmune hemolytic anemia and thrombocytopenia. DESIGN AND METHODS: Seven patients (one with cold agglutinin disease, two with warm antibody autoimmune hemolytic anemia, four with chronic idiopathic thrombocytopenic purpura) previously refractory to conventional treatments were treated with weekly infusions of rituximab, 375 mg/m2, for 4 weeks. Only treatment with steroids, if strictly necessary, was allowed during the period of rituximab administration, but only patients who reached steroid suspension were considered responders. The pharmacokinetics of rituximab were quantified during therapy and the follow-up period. RESULTS: All patients had marked, even if temporary, B-cell depletion. Three patients, 1 with cold agglutinin disease (CAD) and 2 with chronic idiopathic thrombocytopenic purpura (ITP), had a complete hematologic response. In the patient with cold agglutinin disease a decrease in the agglutinin titer was observed. The hematologic improvement was prompt, appearing by the second or third infusion of rituximab. The response duration was CAD 96+, ITP 17+ and 13+ weeks in these 3 patients. Treatment tolerance was satisfactory and no infections or other late events were registered. Serum rituximab concentrations appeared to be similar to those calculated in a historical control group of patients with follicular non-Hodgkin's lymphoma who received rituximab as consolidation of response after first-line CHOP chemotherapy. INTERPRETATION AND CONCLUSIONS: Rituximab appeared to be active and safe in some patients with refractory autoimmune hemolytic anemia and thrombocytopenia. These results, along with data from literature, suggest that this agent may have a therapeutic role in autoimmune diseases. (+info)
Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody.
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By generating four IgG isotype-switch variants of the high affinity 34-3C anti-erythrocyte autoantibody, and comparing them to the IgG variants of the low affinity 4C8 anti-erythrocyte autoantibody that we have previously studied, we evaluated in this study how high affinity binding to erythrocytes influences the pathogenicity of each IgG isotype in relation to the respective contributions of Fcgamma receptor (FcgammaR) and complement. The 34-3C autoantibody opsonizing extensively circulating erythrocytes efficiently activated complement in vivo (IgG2a = IgG2b > IgG3), except for the IgG1 isotype, while the 4C8 IgG autoantibody failed to activate complement. The pathogenicity of the 34-3C autoantibody of IgG2b and IgG3 isotypes was dramatically higher (>200-fold) than that of the corresponding isotypes of the 4C8 antibody. This enhanced activity was highly (IgG2b) or totally (IgG3) dependent on complement. In contrast, erythrocyte-binding affinities only played a minor role in in vivo hemolytic activities of the IgG1 and IgG2a isotypes of 34-3C and 4C8 antibodies, where complement was not or only partially involved, respectively. The remarkably different capacities of four different IgG isotypes of low and high affinity anti-erythrocyte autoantibodies to activate FcgammaR-bearing effector cells and complement in vivo demonstrate the role of autoantibody affinity maturation and of IgG isotype switching in autoantibody-mediated pathology. (+info)