免疫相关性血细胞减少症1例诊治报告

目的：了解免疫相关性血细胞减少症的诊断要点及治疗方法。方法：回顾性分析1例诊断为免疫相关性血细胞减少症患者的 临床资料以及对免疫抑制剂的效果。结果：该患者对免疫抑制剂治疗敏感。结论：免疫相关性血细胞减少症与异常免疫相关,预后良好。     

免疫相关性血细胞减少症

近10余年,在鉴别骨髓衰竭性疾病时,发现了一类由针对骨髓未成熟造血细胞自身抗体介导的2系或3系血细胞减少,暂称之为狭义的"免疫相关性血细胞减少症(IRH)"[1-6]。该症以往多被误诊为不典型再生障碍性贫血(AA)或归于骨髓增生异常综合征(MDS),但按AA或MDS治疗疗效欠佳,迁延不愈。正确认识并诊治此类血细胞减少,不仅有益于患者,而且有益于丰富造血调控学说、纯化     

免疫相关性血细胞减少症的诊断及鉴别诊断

免疫相关性血细胞减少症（immuno-related hemocytopenia,IRH）是近十余年从骨髓衰竭性疾病中分离出的一类新的疾病体系。其发病机制是由于某种未知病原刺激后,主要抗原呈递细胞树突状细胞亚群出现异常,引起下游T淋巴细胞调控失衡,导致B淋巴细胞数量、亚群、功能异常,进而产生仅针对骨髓造血细胞的自身抗体,通过介导巨噬细胞吞噬、激活补体原位溶血或封闭造血细胞膜上的功能蛋白,抑制造血细胞增殖分化而导致骨髓衰竭或无效造血〔1-10〕。临床上,IRH常被误诊为不典型再生障碍性贫血（AA）或骨髓增生异常综合征（MDS）,且疗效欠佳,迁延不愈。因此,正确诊断IRH,将其与其他骨髓衰竭性疾病鉴别开是临床上提高疗效的前提。以往IRH的诊断主要依靠骨髓库姆试验（BMMNC-Coombs试验）或流式细胞术（FCM）检测骨髓造血细胞膜自身抗体,近几年随着检测技术的发展,IRH的诊断亦不断进展,现阐述如下。     

骨髓单个核细胞Coombs试验阳性免疫相关性血细胞减少症72例临床分析

目的总结骨髓单个核细胞Coombs(BMMNC-Coombs)试验阳性免疫相关性血细胞减少症(IRP)患者的临床特征。方法回顾性分析天津医科大学总医院血液科1995年1月至2004年3月诊治的72例骨髓BMMNC-Coombs试验阳性的IRP患者的发病诱因、临床表现、血象及骨髓象、自身抗体类型及免疫治疗效果。结果62.5%(45/72)IRP患者发病前有感染、过敏或妊娠等诱因。72.2%(52/72)患者全血细胞减少;91.7%(66/72)患者有网织红细胞不低的大细胞或正细胞贫血;75.0%(54/72)患者有白细胞减少;18.1%(13/72)患者合并发热;95.8%(69/72)患者可见血小板轻、中、重度减少。以皮肤黏膜出血为主。髂骨骨髓增生活跃和明显活跃[68.1%(49/72)],红系比例增高[51.4%(37/72)]或正常[19.4%(14/72)],骨髓淋巴细胞比例与疗效呈负相关;大部分患者[65.9%(27/41)]胸骨骨髓为增生活跃或明显活跃。BMMNC-Coombs试验皆阳性,检出不同的自身抗体类型和组合方式,56.9%(41/72)患者有溶血迹象,但不符合任何种类的溶血性疾病的诊断标准;42.9%(18/42)患者补体C3降低,19.0%(8/42)患者同时或单独存在补体C4降低。给予免疫抑制和促造血治疗后,3年有效率为87.5%(28/32)。结论IRP是一类获得性自身抗体介导的骨髓细胞破坏或抑制性疾病,BMMNC-Coombs试验阳性IRP患者主要表现为网织红细胞和(或)中性粒细胞比例不低的2系或3系血细胞减少,对免疫抑制和促造血治疗反应好。     

免疫相关性血细胞减少症41例临床分析

目的:观察41例免疫相关性血细胞减少(immunorelated hemocytopenia,IRH)或全血细胞减少症(immunorelated pancytopenia,IRP)患者的临床特点,以提高对本病的认识。方法:分析41例IRH/IRP患者临床表现、血常规、骨髓象、骨髓单个核细胞抗人球蛋白(BMMNC-Coombs)试验、抗核抗体ANA和ENA抗体谱、T淋巴细胞亚群、染色体核型等以及对肾上腺糖皮质激素、环孢素A等免疫抑制剂的治疗反应。结果:本组病例临床主要表现为贫血、出血、感染;血常规呈三系、二系或一系减少,网织红细胞百分比不低;骨髓增生以活跃或明显活跃为主(82.9%),红系比例多增高;BMMNC-Coombs试验阳性率78.0%;除外了再生障碍性贫血(AA)、骨髓增生异常综合征(MDS)、阵发性睡眠性血红蛋白尿(PNH)等疾病;小部分病例(19.5%)并发系统性红斑狼疮(SLE)等自身免疫性疾病;对肾上腺糖皮质激素、环孢素A等治疗有良好反应。结论:IRH/IRP是由于T淋巴细胞调控异常致B淋巴细胞产生针对骨髓未成熟造血细胞的自身抗体而使血细胞减少,BMMNC-Coombs试验对IRH/IRP的...     

全血细胞减少症413例病因分析

全血细胞减少症４１３例病因分析锦州医学院附属医院李淑芳沈阳医学院附属中心医院夏书月全血细胞减少是多种疾病造成的一种周围血象的改变。这种血象异常常见于血液系统疾病，也可见于其它系统疾病。为了解全血细胞减少在血液系统和其它系统疾病中的分布情况和鉴别，现将...     

Graves病伴免疫相关性全血细胞减少症1例

Graves病是一种器官特异性自身免疫病，临床上鲜见Graves病并发免疫相关性全血细胞减少症的报道，我院收治1例，现报告如下。     

环孢素A治疗免疫相关性血细胞减少症血药浓度与疗效关系的研究

目的了解治疗免疫相关性血细胞减少症(IRP)过程中,环孢素A(CsA)血药浓度与疗效的关系。方法对2008年8月至2009年3月天津医科大学总医院血液科50例IRP患者CsA用药血药浓度及疗效进行分析。结果IRP患者空腹CsA血药浓度(C0)(141.3±97.0)μg/L;用药2 h后CsA血药浓度(C2)(437.2±241.9)μg/L。C2≥300μg/L的病例疗效、脱离血制品输注情况、髂骨骨髓增生情况均好于C2<300μg/L的病例。C0≥90μg/L患者的疗效、胸骨巨核数均好于C0<90μg/L的患者。应用CsA同时应用唑类抗真菌药物的病例血清尿素氮(BUN)升高的比例明显高于未用抗真菌药的患者。结论IRP患者CsA血药浓度与疗效相关,C2≥300μg/L及C0≥90μg/L疗效较好。CsA常规用量是安全的,并用唑类抗真菌药可引起肾损害。     

慢性淋巴细胞白血病并发自身免疫性血细胞减少症7例

目的:报道7例慢性淋巴细胞白血病(CLL)并发自身免疫性血细胞减少症,提高对CLL并发自身免疫性血细胞减少症的认识。方法:回顾性分析2000-2007年就诊于中国医学科学院血液病医院的7例CLL并发自身免疫性血细胞减少症患者的症状和体征、实验室检查、治疗及转归,并复习相关文献。结果:6例患者诊断为自身免疫性溶血性贫血(AIHA),1例患者为Evans综合征。3例患者在诊断CLL的同时发现有溶血发作,另4例患者在CLL诊断后中位20.5个月出现溶血。5例患者用瘤可宁加激素的方案治疗,1例患者单用激素治疗,1例患者用单克隆抗体及联合化疗方案治疗。治疗有效6例,无效1例。3例在随访中溶血复发,再次治疗仍有效。1例患者对治疗反应不佳,需输血维持。随访至2008年4月,除1例患者失访外,其余6例患者全部存活。结论:自身免疫性血细胞减少症是CLL较常见的并发症。尽管激素加烷化剂的常规治疗疗效较好,但复发率较高。并发自身免疫性血细胞减少症无明显预后意义。     

全血细胞减少症130例病因分析

全血细胞减少症是一组病因高度异质性的临床综合征,多种疾病均可造成外周血细胞学改变,病因极其广泛,除见于造血系统疾病外,也可见于某些非造血系统疾病。2001年至2008年8月我院共收治全血细胞减少症患者130例,现分析如下。     

Robin Coombs: his life and contribution to haematology and transfusion medicine

Robin Coombs was the last survivor of the distinguished group of immunologists that included Philip Gell, John Humphrey, John Marrack, Peter Medawar and Robert White and who were responsible for the renaissance of British Immunology after the Second World War. He is best remembered for describing the antiglobulin test that bears his name. The antiglobulin test revolutionised the diagnosis of haemolytic diseases and the compatibility testing of blood for transfusion. In all, Coombs authored over 200 scientific papers. Haemagglutination reactions became widely used in the diagnosis of a range of infectious agents. Together with Philip Gell, he devised the classification of allergic reactions; these were published in the textbook "Clinical Aspects of Immunology", which he and Gell first edited in 1963 and which became the leading textbook on medical immunology. Robin Coombs was also one of the founders of the British Society for Immunology.     

Autoimmune haemolytic anaemia presenting 9 years prior to Castleman's disease

Summary Castleman's disease (CD) is a rare disease of unknown aetiology and pathogenesis. We present an unusual case of abdominal CD in whom the first manifestation was an autoimmune haemolytic anaemia presenting 9 years before the diagnosis. The Coombs test became negative 2 months after surgical resection of the mass, suggesting that the mass was the source of the autoantibody. CD may be present in autoimmune haemolytic anaemia in patients with no evidence of any other disease.     

免疫检查点抑制剂相关毒性的机制及其治疗的研究进展

免疫检查点抑制剂在肿瘤治疗中的地位日益突出,显著延长肿瘤患者的生存时间。其关键机制是特异性结合PD-1/PD-L1或CTLA-4靶点,破坏肿瘤免疫耐受,激活淋巴细胞和免疫细胞从而杀灭肿瘤细胞。然而,免疫检查点抑制剂相关毒性的机制还尚未完全明了,故了解其机制并早诊断和早治疗仍是降低毒副反应发生的重要措施。本文对免疫检查点抑制剂相关毒性的机制和治疗的研究进展进行综述。     

1型糖尿病的免疫耐受治疗

1型糖尿病的发病机制是自身免疫性胰岛炎.其胰岛素缺乏是由于胰腺中大量胰岛β细胞被免疫系统攻击所致.通过各种不同的途径建立胰岛β细胞免疫耐受,包括造血干细胞的移植、过继不同功能状态的树突状细胞、口服胰岛素及其相关疫苗的输入、谷氨酸脱羧酶65疫苗、抗CD3、CD20单克隆抗体以及联合免疫干预等免疫耐受治疗,可延缓l型糖尿病...     

Immune dysfunction in cirrhosis

Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function.During the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology mechanisms.Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations.Acute and chronic exposure to bacteria and/or their products,however,can result in variable clinical consequences.The immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic courses.In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis.We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms.Moreover,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease.Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.     

漳州地区献血人群不规则抗体筛查分析

目的:探讨对献血者进行不规则抗体筛查的临床意义及其对保证输血安全的价值。方法:用盐水介质法对153 009例漳州地区献血人群的血浆标本进行不规则抗体筛查,用抗人球蛋白法做进一步鉴定。结果:153 009例标本不规则抗体筛选阳性92例(0.06%)。通过性别分组以及抗人球蛋白法进一步鉴定发现,58 440例女性献血者中检出不规则抗体为61例(0.104%),94 569例男性献血者中检出不规则抗体为31例(0.033%),女性组不规则抗体检出率高于男性组的不规则抗体检出率(P0.01)。同时,检出的不规则抗体中IgM抗体65例(0.042%),IgG抗体27例(0.018%),IgM抗体检出率高于IgG抗体(P0.01)。结论:对献血者进行不规则抗体检测能减少不规则抗体进入受血者体内的可能性,从而有效提高输血的安全性。     

Expression of Dopamine Receptors in Immune Organs and Circulating Immune Cells

The existence of dopamine (DA) D₁- and D₂-like receptors in the rat and pigeon thymus and in human peripheral blood lymphocytes was investigated. The selective D₁-like antagonist [³H]-SCH 23390 was used as a ligand of DA D₁-like receptors (D₁ and D₅ sites). Pharmacological analysis suggests that binding of [³H]-SCH 23390 to sections of thymus and to human peripheral blood lymphocytes belongs mainly to the dopamine D₅ receptor subtype. Light microscope autoradiography, performed in sections of rat and pigeon thymus, revealed that these receptors are located primarily in the cortical layer. DA D₂-like receptors (D₂, D₃ and D₄ sites) were studied in sections of rat thymus and in peripheral blood lymphocytes by using the putative DA D₃ receptor agonist [³H]-7-OH-DPAT as a ligand. Both rat and pigeon thymus and human peripheral blood lymphocytes express a putative DA D₃ receptor. These data are in agreement with recent molecular biology studies performed in human peripheral blood 1ymphocytes. The demonstration of different subtypes of DA receptors in a primary immune organ such as the thymus and in circulating immune cells supports the hypothesis of an involvement of DA in the control of immune function.     

Alcohol Abuse, Alcoholism, and Damage to the Immune System—A Review

Chronic alcohol abuse exacts a major social and medical toll in the United States and other Western countries. One of the least appreciated medical complications of alcohol abuse is altered immune regulation leading to immunodeficiency and autoimmunity. The consequences of the immunodeficiency include increased susceptibility to bacterial pneumonia, tuberculosis, and other infectious diseases. In addition, the chronic alcoholic often has circulating autoantibodies, and recent investigations indicate that the most destructive complications of alcoholism, such as liver disease and liver failure, may have a component of autoimmunity. Current research on altered cytokine balance produced by alcohol is leading to new insights on the regulation of the immune system in the chronic alcoholic. There is also recent development of exciting new techniques designed to improve or restore immune function by manipulation of cytokine balance. Although much remains to be learned, both in the abnormalities produced by alcohol and in the techniques to reverse those abnormalities, current progress reflects a rapidly improving understanding of the basic immune disorders of the alcoholic.     

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

AIM To investigate whether a novel immune function biomarker Quanti FERON-Monitor(QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47(52%) transplanted on the day of their QFM. The remaining 44(48%) were monitored for infections until transplant, death, or census date of 1st February 2014.RESULTS Cirrhotic patients express a median QFM significantly lower than healthy controls(94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed.Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient's immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13(29.5%) experienced a pre-transplant infection a median 20 d(range 2-182) post-test. QFM 214 IU/mL was associated with HR = 4.1(P = 0.01) for infection. A very low QFM 30 IU/mL was significantly associated(P = 0.003) with death in three patients who died while awaiting transplantation(HR = 56.6).CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual's unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.     

Novel Findings in HIV,Immune Reconstitution Disease and Strongyloides stercoralis Infection

We report the successful treatment of an HIV-infected patient with progressive strongyloidiasis as a component of immune reconstitution disease and a review of the literature on this topic. In our experience, pre- and post-antiretroviral therapy intestinal biopsies support a novel mechanism of immune reconstitution disease to Strongyloides stercoralis. We conclude that extended, dual antihelminthic therapy and temporary discontinuation of antiretroviral therapy may be effective in similar patients.