自身免疫性溶血性贫血(AIHA)患者的不同输血方法与效果

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。     

血栓性血小板减少性紫癜37例临床分析

目的:总结分析血栓性血小板减少性紫癜(TTP)患者临床表现,实验室特点及治疗反应,以提高TTP诊断水平和治疗效果。方法:对我院1998年1月～2009年4月期间诊断为TTP的37例患者进行临床特征和治疗转归分析,对所有病例的外周血涂片进行破碎红细胞计数,计数5000个红细胞中所含裂红细胞进行定量。结果:37例患者仅7例(18.9%)出现典型TTP五联征(发热、血小板减少、微血管病性溶血性贫血、神经系统症状和肾脏损害);30例TTP患者(81.1%)出现三联征(血小板减少、微血管病性溶血性贫血、神经系统症状)。本组病例中主要的致病因素为自身免疫性疾患,特发性TTP占56.76%。本组病例外周血涂片100%存在破碎红细胞,均值为4.4%,范围为0.3%～13.4%。本组病例的治疗以血浆置换和输注血浆为主,治疗有效率88.46%;接受血浆输注治疗的患者缓解率仅为18%,而死亡率为82%。结论:TTP诊断仍然依赖临床表现特点,破碎红细胞计数是非常有价值的诊断指标。血浆置换联用血浆输注仍是治疗TTP的首先方法。     

幽门螺杆菌与自身免疫

幽门螺杆菌（Ｈｐ）诱生抗胃Ｈ＾＋Ｋ＾＋－ＡＴＰ酶的自身抗体,这种自身抗体亦可见于自身免疫性胃炎和恶性贫血。很可能Ｈｐ诱发自身免疫过程,从而导致胃萎缩以及自身免疫性胃炎和恶性贫血。     

1型糖尿病发病及防治的免疫学研究进展

1型糖尿病是一种T细胞介导的自身免疫性疾病,胰岛B细胞受到自身免疫破坏而不能合成和分泌胰岛素,临床症状较严重。大量研究表明,1型糖尿病的发病机制与B细胞自身抗原、巨噬细胞、树突状细胞、B淋巴细胞和T淋巴细胞等有关,并且免疫学防治近年来成为1型糖尿病的研究热点。本文就此对1型糖尿病的免疫学相关发病因素和防治做一具体介绍。     

溃疡性结肠炎的病因学研究现状与展望

溃疡性结肠炎 (ulcerative colitis,UC)是一种病因不明的慢性结肠炎 ,病变主要限于结肠的粘膜 ,表现为它的炎症或溃疡 ,多累及直肠和远端结肠 ,但可向远端扩展 ,以及遍及整个结肠。近 10年来 ,UC在我国呈上升趋势 ,它的病因和发病机制很复杂。尽管对它的病因作了不少研究 ,仍未取得突破性进展。虽然如此 ,近年来的成绩还是非常喜人的。现就近几年有关 U C病因研究现状与展望及采用的实验室检查方法作一综述。1　病因学现状1.1　免疫因素　自身免疫异常目前已被普遍认为是 UC的病因之一。U C患者常伴发诸如自身免疫性溶血性贫血、结节性…     

免疫吸附治疗自身免疫疾病的研究进展

自身免疫疾病治疗的常规方法(如免疫抑制剂和血浆置换等)缺乏足够的安全性和有效性,因此,寻找新的治疗方法十分必要。免疫吸附(immunoadsorption,IA)是一种通过选择性或非选择性去除自身致病抗体,从而实现对自身免疫疾病治疗的方法。本文介绍了免疫吸附在扩张型心肌病、特发性膜性肾病、系统性红斑狼疮、重症肌无力4种自身免疫疾病中的研究和临床应用,讨论了该治疗方法的有效性和安全性;同时指出,免疫吸附要在更多的疾病中实现临床应用,还需要在可信度、地域性、样本量等方面做更加深入的临床前试验。     

免疫吸附治疗自身免疫疾病的研究进展

自身免疫疾病治疗的常规方法(如免疫抑制剂和血浆置换等)缺乏足够的安全性和有效性,因此,寻找新的治疗方法十分必要。免疫吸附(immunoadsorption,IA)是一种通过选择性或非选择性去除自身致病抗体,从而实现对自身免疫疾病治疗的方法。本文介绍了免疫吸附在扩张型心肌病、特发性膜性肾病、系统性红斑狼疮、重症肌无力4种自身免疫疾病中的研究和临床应用,讨论了该治疗方法的有效性和安全性;同时指出,免疫吸附要在更多的疾病中实现临床应用,还需要在可信度、地域性、样本量等方面做更加深入的临床前试验。     

综述与专论：免疫吸附治疗自身免疫疾病的研究进展

自身免疫疾病治疗的常规方法 (如免疫抑制剂和血浆置换等)缺乏足够的安全性和有效性,因此,寻找新的治疗方法十分必要。免疫吸附(immunoadsorption,IA)是一种通过选择性或非选择性去除自身致病抗体,从而实现对自身免疫疾病治疗的方法。本文介绍了免疫吸附在扩张型心肌病、特发性膜性肾病、系统性红斑狼疮、重症肌无力4种自身免疫疾病中的研究和临床应用,讨论了该治疗方法的有效性和安全性;同时指出,免疫吸附要在更多的疾病中实现临床应用,还需要在可信度、地域性、样本量等方面做更加深入的临床前试验。     

TLR/MyD88信号通路与自身免疫性疾病

Toll样受体(Toll-like receptor,TLR)是近年来发现的一类模式识别受体,通过识别病原相关分子模式(pathogen-associated molecular pattern,PAMP),激活天然免疫.TLR信号还通过上调抗原提呈细胞(antigen presenting cells,APC)表面共刺激分子及APC分泌的炎症细胞因子调节获得性免疫.TLR/MyD88信号在自身免疫性疾病的发病过程中起重要作用.本文介绍了TLR/MYD88信号通路及其在自身免疫病如实验性自身免疫脑脊髓膜炎、类风湿性关节炎、实验性自身免疫性葡萄膜炎、实验性自身免疫性心肌炎和自身免疫性肾小球肾炎等发生发展中的作用.     

系统性红斑狼疮早发动脉粥样硬化的研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是累及多系统多器官的自身免疫病,近年来的流行病学研究发现SLE患者已成为心血管痰病(cardiovascular disease,CVD)的高危人群,早发动脉粥样硬化(atherosclerosis,AS)是SLE患者最常见的CVD之一.传统心血管危险因素如高血压、高脂血症、肥胖等不能完全解释SLE早发AS,非传统危险因素如自身抗体、免疫复舍物、内皮功能障碍、系统性炎症反应等在SLE早发AS的发病机制中的作用越来越受到关注,深入研究这些非传统危险因素在SLE早发AS的致病作用,将有助于防治SLE患者的CVD,提高SLE患者生存率.     

再循环T细胞昼夜节律现象的数学模型

根据人体和小鼠免疫细胞昼夜节律实验结果,提出皮质类激素对淋巴结和脾脏中T细胞再循环产生不同作用的假设,建立了皮质类激素作用下的T细胞在不同外周淋巴器官（淋巴结、脾脏）与血液之间再循环过程的数学模型,讨论了皮质类激素作用的强度、有关参量的取值范围和模型对参数的依赖性. 模型能够解释参与再循环的T细胞在淋巴结、脾脏与血液中的稳定振荡行为,得到的数值模拟结果与免疫系统生物节律实验结果一致.     

Characterization of zebrafish merlot/chablis as non-mammalian vertebrate models for severe congenital anemia due to protein 4.1 deficiency

The red blood cell membrane skeleton is an elaborate and organized network of structural proteins that interacts with the lipid bilayer and transmembrane proteins to maintain red blood cell morphology, membrane deformability and mechanical stability. A crucial component of red blood cell membrane skeleton is the erythroid specific protein 4.1R, which anchors the spectrin-actin based cytoskeleton to the plasma membrane. Qualitative and quantitative defects in protein 4.1R result in congenital red cell membrane disorders characterized by reduced cellular deformability and abnormal cell morphology. The zebrafish mutants merlot (mot) and chablis (cha) exhibit severe hemolytic anemia characterized by abnormal cell morphology and increased osmotic fragility. The phenotypic analysis of merlot indicates severe hemolysis of mutant red blood cells, consistent with the observed cardiomegaly, splenomegaly, elevated bilirubin levels and erythroid hyperplasia in the kidneys. The result of electron microscopic analysis demonstrates that mot red blood cells have membrane abnormalities and exhibit a severe loss of cortical membrane organization. Using positional cloning techniques and a candidate gene approach, we demonstrate that merlot and chablis are allelic and encode the zebrafish erythroid specific protein 4.1R. We show that mutant cDNAs from both alleles harbor nonsense point mutations, resulting in premature stop codons. This work presents merlot/chablis as the first characterized non-mammalian vertebrate models of hereditary anemia due to a defect in protein 4.1R integrity.     

The negative regulation of red cell mass by neocytolysis: physiologic and pathophysiologic manifestations.

We have uncovered a physiologic process which negatively regulates the red cell mass by selectively hemolyzing young circulating red blood cells. This allows fine control of the number of circulating red blood cells under steady-state conditions and relatively rapid adaptation to new environments. Neocytolysis is initiated by a fall in erythropoietin levels, so this hormone remains the major regulator of red cell mass both with anemia and with red cell excess. Physiologic situations in which there is increased neocytolysis include the emergence of newborns from the hypoxic uterine environment and the descent of polycythemic high-altitude dwellers to sea level. The process first became apparent while investigating the mechanism of the anemia that invariably occurs after spaceflight. Astronauts experience acute central plethora on entering microgravity resulting in erythropoietin suppression and neocytolysis, but the reduced blood volume and red cell mass become suddenly maladaptive on re-entry to earth's gravity. The pathologic erythropoietin deficiency of renal disease precipitates neocytolysis, which explains the prolongation of red cell survival consistently resulting from erythropoietin therapy and points to optimally efficient erythropoietin dosing schedules. Implications should extend to a number of other physiologic and pathologic situations including polycythemias, hemolytic anemias, 'blood-doping' by elite athletes, and oxygen therapy. It is likely that erythropoietin influences endothelial cells which in turn signal reticuloendothelial phagocytes to destroy or permit the survival of young red cells marked by surface molecules. Ongoing studies to identify the molecular targets and cytokine intermediaries should facilitate detection, dissection and eventual therapeutic manipulation of the process.     

Effect of adrenalectomy on rat peritoneal macrophage response

Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. In contrast to other hormonal systems no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Glucocorticoids are known to interfere with the ability of the macrophage not only to induce and amplify an immune response but also to inhibit macrophage inflammatory effector functions. Although the actual immunocompetence of animals undergoing endocrine gland ectomy has never been directly studied, there is no doubt that adrenal hormones are deeply involved in the development and maintenance of the immunitory functions and this may in turn influence the inflammatory reaction. To study the effect of endogenous glucocorticoids on the functions of rat peritoneal macrophages and induction of humoral immune response we observed some of the rat peritoneal macrophage effector functions, provided that endogenous glucocorticoids are depicted by adrenalectomy. The mean phagocytic index (PI) of control macrophage (Mphi) is increased from 23,825 +/- 427 to 31,895 +/- 83 after adrenalectomy (P < or = 0.001). Intracellular killing capacity in control cell is 82% which is found to be 73% in case of adrenalectomised cell (p < 0.05). The amount of nitric oxide released from control Mphi 20.25 +/- 1 microM following adrenalectomy shows the amount of nitric oxide release was 18.25 microM (p < or = 0.01 ). The percentage of DNA fragmentation in control Mphi was 68.82 +/- 4 which was reduced to 56.76 +/- 1 after adrenalectomy (p < or = 0.01). In sheep red blood cell (SRBC) immunised and adrenalectomised animal, agglutination titre was obtained at lowest antibody concentration (1 : 128) whereas serum from SRBC immunised normal rats showed early agglutination (1: 32). Endogenous glucocorticoid depleted rats show enhanced phagocytic capacity, antibody raising capacity as well as on the other hand adrenal hormone insufficiency reduces the intracellular killing capacity, nitric oxide (NO) release, improper cell maturation and heightens the probability of infection. These observations demonstrate a counter-regulatory system via glucocorticoid that functions to control inflammatory and immune responses.     

Low red cell production may protect against severe anemia during a malaria infection—Insights from modeling

The malaria parasite causes lysis of red blood cells, resulting in anemia, a major cause of mortality and morbidity. Intuitively, one would expect the production of red blood cells to increase in order to compensate for this loss. However, it has been observed that this response is weaker than would be expected. Furthermore, iron supplementation for iron deficient children in malaria endemic regions can paradoxically adversely affect the clinical outcome of malaria infection. A possible explanation may lie in the preference that some malaria parasites show for infecting immature red blood cells (reticulocytes). In the presence of a parasite preference for immature red cells, a rise in red cell production can ‘fuel the fire’ of infection by increasing the availability of the parasite's preferred target cell.We present a mathematical model of red blood cell production and infection in order to explore this hypothesis. We assess the effect of varying the reticulocyte replacement rate and preference of the parasite for reticulocytes on four key outcome measures assessing anemia and parasitemia.For a given level of parasite preference for reticulocytes we uncover an optimal erythropoietic response which minimizes disease severity. Increasing red blood cell production much above this optimum confers no benefit to the patient, and in fact can increase the degree of anemia and parasitemia. These conclusions are consistent with epidemiological studies demonstrating that both iron deficiency and anemia are protective against severe malaria, whilst iron supplementation in malaria endemic regions is with an increased number of malaria related adverse effects. Thus, suppression of red blood cell production, rather than being an unfortunate side effect of inflammation, may be a host protective effect against severe malarial anemia.     

Babesia microti: Biochemistry and function of hamster erythrocytes infected from a human source

Babesia microti, a protozoan parasite of mammalian erythrocytes was obtained from the blood of an infected human and maintained in golden hamsters, in which a parasitemia of 70% was obtained regularly. The hamsters' response—a subacute, hemolytic anemia—was studied with regard to oxygen affinity and red cell organic phosphate content. In addition, the reduced glutathione status of infected erythrocytes was observed because of the possible importance of this metabolite to parasite growth and red cell integrity. Infected animals developed a severe anemia with reticulocytosis; there occurred a 4-mm decrease in whole blood oxygen affinity without any change in erythrocytes' 2,3-diphosphoglycerate levels. The glutathione content of the infected animals' erythrocytes increased twofold during the course of the infection. In uninfected animals, in which anemia and reticulocytosis had been produced by bleeding, all changes seen in infected animals were reproduced. It was concluded that the changes in the infected animals were due to the anemia and reticulocytosis alone, and that the parasite played no role in these changes apart from being a cause of anemia and reticulocytosis.     

Decreased Hematocrit-To-Viscosity Ratio and Increased Lactate Dehydrogenase Level in Patients with Sickle Cell Anemia and Recurrent Leg Ulcers

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study – were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.     

Evaluating treatment of hepatitis C for hemolytic anemia management

The combination therapy of antiviral peg-interferon and ribavirin has evolved as one of the better treatments for hepatitis C. In spite of its success in controlling hepatitis C infection, it has also been associated with treatment-related adverse side effects. The most common and life threatening among them is hemolytic anemia, necessitating dose reduction or therapy cessation. The presence of this side effect leads to a trade-off between continuing the treatment and exacerbating the side effects versus decreasing dosage to relieve severe side effects while allowing the disease to progress. The drug epoietin (epoetin) is often administered to stimulate the production of red blood cells (RBC) in the bone marrow, in order to allow treatment without anemia. This paper uses mathematical models to study the effect of combination therapy in light of anemia. In order to achieve this we introduce RBC concentration and amount of drug in the body as state variables in the usual immunological virus infection model. Analysis of this model provides a quantification of the amount of drug a body can tolerate without succumbing to hemolytic anemia. Indirect estimation of parameters allow us to calculate the necessary increment in RBC production to be ?2.3 times the patient’s original RBC production rate to sustain the entire course of treatment without encountering anemia in a sensitive patient.     

Endogenous cardiac glycosides, a new class of steroid hormones.

The search for endogenous digitalis has led to the isolation of ouabain as well as several additional cardiotonic steroids of the cardenolide and bufadienolide type from blood, adrenals, and hypothalamus. The concentration of endogenous ouabain is elevated in blood upon increased Na(+) uptake, hypoxia, and physical exercise. Changes in blood levels of ouabain upon physical exercise occur rapidly. Adrenal cortical cells in tissue culture release ouabain upon addition of angiotensin II and epinephrine, and it is thought that ouabain is released from adrenal cortex in vivo. Ouabain levels in blood are elevated in 50% of Caucasians with low-renin hypertension. Infusion over several weeks of low concentrations of ouabain, but not of digoxin, induces hypertension in rats. A digoxin-like compound, which has been isolated from human urine and adrenals, as well various other endogenous cardiac glycosides may counterbalance their actions within a regulatory framework of water and salt metabolism. Marinobufagenin, for instance, whose concentration is increased after cardiac infarction, may show natriuretic properties because it inhibits the alpha1 isoform of Na(+)/K(+)-ATPase, the main sodium pump isoform of the kidney, much better than other sodium pump isoforms. In analogy to other steroid hormones, cardiotonic steroid hormones in blood are bound to a specific cardiac glycoside binding globulin. The discovery of ouabain as a new adrenal hormone affecting Na(+) metabolism and the development of the new ouabain antagonist PST 2238 allows for new possibilities for the therapy of hypertension and congestive heart failure. This will lead in turn to a better understanding of the disease on a physiological and endocrinological level and of the action of ouabain on the cellular level as a signal that is transduced to the plasma membrane as well as to the cell nucleus.