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1.
Although it is established that failure of regulatory mechanisms underlies many autoimmune diseases, the stimuli that activate autoreactive lymphocytes remain poorly understood. Defining these stimuli will lead to therapeutic strategies for autoimmune diseases. IL-2-deficient mice develop spontaneous autoimmunity, because of a deficiency of regulatory T cells, and on the BALB/c background, they rapidly die from autoimmune hemolytic anemia. To define the importance of costimulatory pathways in various components of this autoimmune disorder, we first intercrossed IL-2-deficient mice with mice lacking CD28 or CD40L. Elimination of CD28 reduced the activation of autoreactive T cells and lymphoproliferation as well as production of autoantibodies, whereas elimination of CD40L reduced autoantibody production without affecting T cell expansion and accumulation. To examine the role of IL-7, we blocked IL-7R signaling with neutralizing Abs. This treatment inhibited the production of autoantibodies and the development of autoimmune hemolytic anemia. Together, these data indicate that specific costimulatory and cytokine signals are critical for the spontaneous autoantibody-mediated disease that develops in IL-2-deficient mice.  相似文献   

2.
Activity of S-adenosylmethionine-dependent arginine methyltransferase was substantially higher in sonicated bone marrow samples from 6 patients with chronic erythremic myelosis than in bone marrow from 3 patients with untreated pernicious anemia, 2 patients with autoimmune hemolytic anemia, and 4 normal persons. Increased activity of this enzyme may be one of the factors contributing to the pathogenesis fo methylated arginines in histones of erythroblasts from patients with chronic erythremic myelosis.  相似文献   

3.

Introduction

Metformin is a widely prescribed biguanide antidiabetic drug that has been implicated as a cause of hemolytic anemia in three previous case reports. We report a case of rapidly fatal hemolysis that was temporally associated with the initiation of metformin treatment for diabetes. Clinicians need to be aware of this rare but potentially serious side effect of metformin.

Case presentation

A 56-year-old Caucasian man with type 2 diabetes mellitus was started on metformin to improve glycemic control. Shortly afterwards, he developed progressive fatigue, exertional dyspnea, cranberry-colored urine and jaundice. Laboratory studies showed severe hemolysis, with a drop in hemoglobin from 14.7 to 6.6 g/dl over 4 days, markedly elevated lactate dehydrogenase, bilirubin and reticulocyte counts, and a low haptoglobin level. A peripheral blood smear showed no schistocytes, and a direct Coombs test was positive for anti-IgG and negative for anti-C3. Despite corticosteroid treatment and transfusion of packed red blood cells, the patient developed increasing dyspnea, hypotension, further decline in hemoglobin to 3.3 g/dl, and fatal cardiorespiratory arrest 12 hours after admission.

Conclusion

The serologic findings in this case suggest an autoimmune hemolytic anemia, caused either by a drug-induced autoantibody or a warm autoantibody. Based on the temporal association with metformin and the lack of other clear precipitating causes, we propose that metformin-induced hemolysis with a drug-induced autoantibody is a strong possibility. This mechanism differs from a previously described case with a possible antibody to the erythrocyte-drug complex. It has been shown, however, that hemolysis may occur via multiple mechanisms from the same drug. Clinicians should consider the possibility of metformin-associated immune hemolytic anemia in patients with otherwise unexplained hemolysis.
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4.
NZB mice spontaneously develop an autoimmune disease characterized by autoimmune hemolytic anemia, thymic atrophy, lymphoid hyperplasia, and hypergammaglobulinemia. The aim of this study was to examine the hypothesis that cryoglobulins may have an immunoregulatory effect on the autoimmune process. The effect of human monoclonal IgM cryoglobulin preparations (including Cryo13, Cryo14, and Cryo16) isolated from the serum of patients with Waldenstr?m's macroglobulinemia on the autoimmune disease of NZB mice was therefore studied. The effect of cryoglobulin preparations was evaluated on several disease parameters, i.e., survival, severity of anemia, and serum IgM and IgG levels (hypergammaglobulinemia). We found that immunization of NZB mice with Cryo13 at 3 months of age delayed the course of the disease, whereas Cryo14 and Cryo16 were ineffective. Furthermore, the effect of Cryo13 was long lasting. On the other hand, Cryo13 was able to react with 8 of 32 mouse monoclonal natural IgM autoantibodies. In contrast, Cryo14 was able to bind only 2 and Cryo16 none of these mouse monoclonal IgM antibodies. These results indicate that, in this model of autoimmune pathology, the beneficial effect of Cryo13 is mediated by its idiotypic interaction with the murine natural autoantibody network.  相似文献   

5.
目的:探讨不同输血方法治疗自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)的效果。方法:2017年1月-2018年12月选择在本院血液科诊治的64例自身免疫性溶血性贫血患儿,根据输血方法的不同分为观察组与对照组,各32例。观察组给予洗涤红细胞输注治疗,对照组给予非洗涤红细胞(悬浮红细胞)输注治疗,记录两组输血效果。结果:治疗后4 w观察组的总有效率显著高于对照组(100.0%vs.87.5%,P0.05)。两组治疗后4 w的红细胞计数与血红蛋白都显著高于治疗前,且观察组显著高于对照组(P0.05)。观察组的吸氧、机械通气、住院时间都显著少于对照组(P0.05)。观察组治疗过程的过敏反应、发热反应、紫癜等不良反应发生率显著低于对照组(3.1%vs. 21.9%,P0.05)。结论:洗涤红细胞输注治疗自身免疫性溶血性贫血患儿能促进机体红细胞计数与血红蛋白恢复正常,减少不良反应的发生,提高治疗效果与促进患儿康复。  相似文献   

6.
Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic EPO activity forms an attractive therapeutic target in infection and inflammation.  相似文献   

7.
The mechanisms underlying the frequent association between chronic lymphocytic leukemia (CLL) and autoimmune hemolytic anemia are currently unclear. The erythrocyte protein band 3 (B3) is one of the most frequently targeted Ags in autoimmune hemolytic anemia. In this study, we show that CLL cells specifically recognize B3 through a still unidentified receptor. B3 interaction with CLL cells involves the recognition of its N-terminal domain and leads to its internalization. Interestingly, when binding of erythrocyte-derived vesicles as found physiologically in blood was assessed, we observed that CLL cells could only interact with inside-out vesicles, being this interaction strongly dependent on the recognition of the N-terminal portion of B3. We then examined T cell responses to B3 using circulating CLL cells as APCs. Resting B3-pulsed CLL cells were unable to induce T cell proliferation. However, when deficient costimulation was overcome by CD40 engagement, B3-pulsed CLL cells were capable of activating CD4(+) T cells in a HLA-DR-dependent fashion. Therefore, our work shows that CLL cells can specifically bind, capture, and present B3 to T cells when in an activated state, an ability that could allow the neoplastic clone to trigger the autoaggressive process against erythrocytes.  相似文献   

8.
We investigated the relationship between the increased cell diameter of Lyt-2+ T cells and the development of autoimmune disease in aging NZB and NZB X NZW F1 hybrid (BW) mice. Individual animals were analyzed for Lyt-2+ T cell size (by narrow-angle forward light scatter), anti-erythrocyte autoantibodies, anemia, proteinuria, and splenomegaly. The peak light scatter of the Lyt-2+ T cells correlated with the level of anti-erythrocyte autoantibodies and severity of hemolytic anemia, but not with proteinuria or splenomegaly. The cell size of this T cell subset did not increase in old BW or in NZB mice homozygous for the xid gene (NZB.xid). The in vivo administration of bacterial lipopolysaccharide to young NZB mice did not stimulate the enlargement of Lyt-2+ T cells. Ly-2+ T cells from old NZB mice could be stimulated by concanavalin A (Con A) to express interleukin 2 (IL 2) receptors and to synthesize DNA in vitro. However, in vivo administration of Con A to old NZB mice did not induce the expression of IL 2 receptors on Lyt-2+ T cells. Further, in vivo T suppressor function was impaired in old NZB mice with enlarged Lyt-2+ T cells. Thus, the enlargement of Lyt-2+ T cells in old NZB mice appears related to impaired T cell function in vivo and is associated with the development of anti-erythrocyte autoantibodies and autoimmune hemolytic anemia.  相似文献   

9.
Deficiencies of glycolytic enzymes as a possible cause of hemolytic anemia   总被引:5,自引:0,他引:5  
The critical minimum values of Na,K-ATPase and glycolytic enzyme activities at which the erythrocyte viability is lost were calculated using the mathematical model of the erythrocyte, which included all reactions of glycolysis, adenylate metabolism, ionic balance, and osmotic regulation of erythrocyte volume. The criterion for cell death was an increase in its volume to the level at which it is sequestrated from the circulation or is lysed. In hemolytic anemia associated with hexokinase or pyruvate kinase deficiency, activities of these enzymes measured in patient erythrocytes appeared to be close to the calculated critical values. By contrast, in hemolytic anemia associated with phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, activities of these enzymes measured in patient erythrocytes were significantly greater than the calculated critical values. In this case, if the deficient enzyme were stable, i.e. its activity in the cell were low, but constant in time, the deficiency observed would not account for the erythrocyte destruction observed and the development of hemolytic anemia. It was shown, however, that in phosphofructokinase, glucosephosphate isomerase, triosephosphate isomerase, or phosphoglycerate kinase deficiency, hemolytic anemia can arise because of the instability of these enzymes in time.  相似文献   

10.
Acetylcholinesterase of human erythrocytes from healthy donors and from patients with hematological disorders was analysed in a search for differential membrane parameters. Two substrates were used to estimate the exposure of acetylcholinesterase active site in the membrane: phenylacetate, a hydrophobic substrate, to determine total enzyme activity, and acetylcholine, an ionic substrate, to measure the externally reactive enzyme. The sensitivity of acetylcholinesterase to added stearic acid was also analysed. Three categories of the disorders studied were discerned: (a) The erythrocyte acetylcholinesterase profile was indistinguishable from normal control in beta-thalassemia minor and groups of patients with autoimmune hemolytic anemia or congenital dyserythropoietic anemia type II. (b) A marked decline in acetylcholinesterase with both substrates and reduced sensitivity to stearic acid were exhibited by the erythrocytes of paroxysmal nocturnal hemoglobinuria, beta-thalassemia major and other autoimmune hemolytic anemia and congenital dyserythropoietic anemia type II patients. Normal erythrocytes, either aged or pretreated to 50 degrees C, also showed similar characteristics. (c) Hereditary spherocytosis was singly differentiated by an elevated acetylcholinesterase activity with acetylthiocholine and by a vastly diminished sensitivity to stearic acid, while activity with phenylacetate was equal to control. This distinct profile may reflect the unique organization of the erythrocyte membrane in hereditary spherocytosis.  相似文献   

11.
Summary Clinical, familial and biochemical studies from six unrelated Spanish patients with hereditary hemolytic anemia and erythrocyte pyruvate-kinase (PK) deficiency are described. A remarkable molecular heterogeneity of mutant PK variants involving kinetic properties, molecular stability or electrophoretic mobility is demonstrated. In two patients whose PK variants showed abnormal electrophoretic pattern, and strongly aberrant kinetic properties, a chronic hemolytic anemia assciated with several other clinical manifestations of chronic hemolysis occurred. In patients whose PK variants showed less abnormal kinetic and electrophoretic characteristics, there was only moderate or mild hemolytic anemia. One patient's PK variant with no obvious kinetic or electrophoretic alterations, showed a markedly decreased heat stability with severe diminution of antigenic concentration of the enzyme. This patient presented a spectacular clinical and hematological improvement after splenectomy.The purpose of the present study is to describe six new PK variants of Spanish origin. In addition, an attempt is made to find relationships between molecular abnormalities of mutant PK variants and the severity of hemolytic anemia, in these patients. The possible role of some kinetic alterations, such as fructose diphosphate (FDP) activation or ATP inhibition of PK variants, in the clinical manifestations of chronic hemolysis is also suggested.  相似文献   

12.

Background

Gastric duplication cysts are uncommon congenital anomalies found primarily in children and rarely seen in the adult population. Accurate diagnosis of cysts before resection is difficult even using the most advanced imaging techniques.

Case presentation

In this report, we describe a 28-year-old Moroccan patient with a history of autoimmune hemolytic anemia who presented with an asymptomatic abdominal cystic mass detected during abdominal computed tomography performed before splenectomy. Magnetic resonance imaging performed for accurate characterization showed a high-signal-intensity cystic mass on T2-weighted images, located between the patient’s stomach and spleen. The patient underwent a complete cyst resection during exploratory laparotomy. The histological examination showed a cyst lined by three different epithelia with bundles of smooth muscle, which suggested a gastric duplication cyst.

Conclusions

We report a case of gastric cyst duplication in an adult with autoimmune hemolytic anemia, and we discuss this rare association, radiological findings, and the unique histological findings of this case.
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13.
Murine phagocytes express three different activating IgG FcgammaR: FcgammaRI is specific for IgG2a; FcgammaRIII for IgG1, IgG2a, and IgG2b; and FcgammaRIV for IgG2a and IgG2b. Although the role of FcgammaRIII in IgG1 and IgG2a anti-RBC-induced autoimmune hemolytic anemia (AIHA) is well documented, the contribution of FcgammaRI and FcgammaRIV to the development of IgG2a- and IgG2b-induced anemia has not yet been defined. In the present study, using mice deficient in FcgammaRI, FcgammaRIII, and C3, in combination with an FcgammaRIV-blocking mAb, we assessed the respective roles of these three FcgammaR in the development of mild and severe AIHA induced by two different doses (50 and 200 microg) of the IgG2a and IgG2b subclasses of the 34-3C anti-RBC monoclonal autoantibody. We observed that the development of mild anemia induced by a low dose of 34-3C IgG2a autoantibody was highly dependent on FcgammaRIII, while FcgammaRI and FcgammaRIV additionally contributed to the development of severe anemia induced by a high dose of this subclass. In contrast, the development of both mild and severe anemia induced by 34-3C IgG2b was dependent on FcgammaRIII and FcgammaRIV. Our results indicate differential roles of the three activating FcgammaR in IgG2a- and IgG2b-mediated AIHA.  相似文献   

14.
A family with congenital non-spherocytic hemolytic anemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency was studied. Two females, heterozygous for the enzyme deficency, had evidence of a hemolytic anemia. The results of chromium-51 erythrocyte life span studies prior to, during, and after periods of primaquine administration suggested that the hemolytic anemia in these women was due to the presence of two populations of red blood cells in their circulation. One population had normal G6PD levels and a normal life span, whereas the other had diminished enzyme activity and a shortened life span.In vitro metabolic studies of the erythrocytes of a heterozygous female and a hemizygous male suggested that, in spite of G6PD deficiency, the synthesis and breakdown of adenosine triphosphate and 2,3-diphosphoglyceric acid was similar to that in normal erythrocytes.  相似文献   

15.
Rosette-formation with auto- and allogeneic red blood cells was applied to detection of human leucocyte subpopulations interacting with Sendai virus (V-rosettes). It was shown that the majority of V-rosette-forming cells appeared to be monocytes. T lymphocytes did not take part in V-rosette-formation since selective elimination of T cells from the mononuclear cells population did not lead to reduction of but increased the number of V-rosettes. Enrichment of cell suspension with B lymphocytes was followed by a rise in the number of V-rosettes thereby allowing the attribution of B lymphocytes along with monocytes to the cell population interacting with virus. The results suggest that ability of virus-exposed immunocompetent cells to react with their own red blood cells may lie at the basis of the development of autoimmune hemolytic anemia and other autoimmune diseases.  相似文献   

16.
Summary A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was reported. The patient, a 6-year-old Japanese male, was noticed to have hemolytic anemia soon after birth, and a diagnosis of G6PD deficiency was made at the age of 2. He had episodes of hemolytic crisis several times after upper respiratory infection. G6PD activity of the patient was 5.5% of normal. The enzymatic characteristics were examined when he was 5 years old, and his G6PD showed faster-than-normal electrophoretic mobility, low Km G6P, high Km NADP, low Ki NADPH, normal utilization of substrate analogues, heat instability, and a normal pH optimum curve. From these results, this was considered to be a new variant and was designated G6PD Nagano. Infection-induced hemolysis and chronic hemolytic anemia seem to be due to markedly impaired enzyme activity and thermal instability.  相似文献   

17.
We attempted to define the etiology of anemia in SIV-infected rhesus macaques. Bone marrow culture showed significantly decreased (75% reduction) burst forming unit-erythroid (BFU-E) growth in end-stage SIV+ “sick” animals. Direct antiglobulin tests (DAT) were positive in nine of 35 SIV+ “well” and 14 of 14 SIV+ “sick” monkeys (0 of 25 control animals had positive DATs). In animals with a positive DAT, moderate to severe anemia was observed, as was increased LDH and spherocytosis. Erythropoietin was measured in four control, eight SIV+ “well” and five SIV+ “sick” animals with mean levels of 4.0, 15.4, and 1176 mU/mL (r = .94) in the three groups. These data suggest that the cause of anemia in the SIV-infected rhesus macaque is multifactorial, that there may be a defect in erythropoiesis, and that, serologically, an IgG mediated autoimmune hemolytic anemia is also present.  相似文献   

18.
R. K. Smiley 《CMAJ》1964,90(23):1287-1292
Three patients with erythroblastic hypoplasia were observed for prolonged periods. In one patient, the phenomenon recurred on three occasions over a 12-year period. In the second, erythroblastic hypoplasia accompanied acute hemolytic anemia of the autoimmune type. The third patient had congenital erythroblastic hypoplasia which was observed for 14 years without remission. From the prolonged periods of observation of these three patients, it is concluded that the phenomenon of erythroblastic hypoplasia may develop abruptly, persist for variable periods of time, remit spontaneously and recur unpredictably. A total of four remissions observed in two patients were believed to be spontaneous and not a result of any of the forms of treatment administered. No remission has occurred in a 14-year-old boy with congenital erythroblastic hypoplasia. A classification of erythroblastic hypoplasia is proposed, based on the clinical circumstances in which the phenomenon has been encountered.  相似文献   

19.
The hemolytic anemias of unknown cause can be separated into two main groups: (1) those produced by a defect in cell structure, which is usually hereditary, and (2) those due to a hemolysin of immune-body type.The hemolytic anemias associated with hypersensitivity to drugs and disease processes such as leukemia are less well understood and need further investigation.Splenectomy is the only effective treatment in congenital hemolytic jaundice and in acquired hemolytic anemia; the operation should be carried out promptly in most cases. Transfusion may be used in all varieties of hemolytic disease and is the only effective form of therapy in sickle-cell anemia and paroxysmal nocturnal hemoglobinuria.  相似文献   

20.
S B Reddy  J L Pater  J Pym  P W Armstrong 《CMAJ》1984,131(12):1469-1470
Hemolytic anemia is a relatively common complication after the replacement of cardiac valves with mechanical prostheses; the prevalence rate varies from 38% to 85%, depending on the prosthesis implanted. However, cardiac valves fabricated from biologic material are associated with a reduced incidence of hemolytic anemia, and to the authors'' knowledge this report is the first to document hemolytic anemia in a patient who had the mitral valve replaced with an Ionescu-Shiley valve. The anemia was not associated with evidence of hemodynamically important mitral regurgitation and was ultimately controlled by iron and folate supplements.  相似文献   

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