Autoimmunity in transfusion babesiosis: A spectrum of clinical presentations

Transfusion‐acquired babesiosis can be an asymptomatic or self‐limited febrile hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant course with the development of life‐threatening complications may be seen in immunocompromised or splenectomized patients. As in malaria, erythrocyte parasitemia is often associated with nonimmune hemolysis, and can be treated with erythrocytapheresis. Just as warm autoantibodies have been reported in malaria infection, the development of autoantibody‐mediated immune hemolysis has been reported in babesiosis. We treated a previously healthy male with multiple injuries from a motor vehicle accident necessitating massive transfusion. Late in the hospitalization, his blood smear revealed Babesia microti, confirmed by PCR study and serology. This was eventually traced to a unit of blood from an asymptomatic blood donor that was transfused during his initial trauma care. Specific antibiotic therapy was begun, and severe hemolysis from a high parasite burden required red blood cell exchange which led to rapid abatement of the hemolysis. He had a positive DAT (IgG with a pan‐reactive eluate) but no serum autoantibody. This persisted for 10 days following cessation of hemolysis, and became negative while still on antibiotics while his parasite burden became undetectable. Reports of autoimmunity associated with community acquired babesiosis often have severe hemolysis from their autoantibodies, but our case shows that autoantibodies may also follow transfusion‐acquired babesiosis. The nature of the autoantigen is unknown. J. Clin. Apheresis, 2010. © 2010 Wiley‐Liss, Inc.     

DNA and Heparin Alter the Internalization Process of Anti-DNA Monoclonal Antibodies According to Patterns Typical of Both the Charged Molecule and the Antibody

The internalization into CHO-K1 fibroblasts of three polyreactive monoclonal IgG2a anti-DNA autoantibodies (mAbs), F14.6, J20.8 and F4.1, isolated from the same unimmunized (NZBxNZW) F1 mouse, and synthetic peptides derived from F4.1 was studied using a technique which quantifies nuclear accumulation. The localization of the mAbs was intranuclear. We compared the influence of two negatively-charged molecules, DNA or heparin. At low concentrations, DNA had dual effects-inhibitory or stimulatory-depending on the mAb. Heparin was inhibitory or had no effect. The possibility that proteoglycans are 'receptors' recognized by anti-DNA mAbs which bind through heparin-sensitive reactions, was explored. Only F4.1 internalization was partly inhibited in glycosaminoglycan-deficient cells. We propose that the complex alterations of internalization patterns of these polyreactive mAbs by the two negatively charged molecules can be explained by (a) the potential of polyreactive mAbs to bind to various charge (or conformation-) dependent 'receptors', (b) the potential of a subclass of mAbs complexed with DNA to utilize additional 'receptor(s)'. Glycosaminoglycans were required for internalization of F4.1-derived peptides, which remained extranuclear, suggesting that nuclear internalization of mAb F4.1 is a multistep process that requires certain sequences present on the intact mAb.     

A case of acquired autoimmune bullous disease associated with IgM macroglobulinaemia.

A variety of autoimmune bullous dermatoses have been reported to develop in association with lymphoproliferative disorders. We report a patient with IgM macroglobulinaemia, who presented with a skin fragility similar to but somewhat milder than that seen in epidermolysis bullosa acquisita. Immunofluorescence detected circulating IgM autoantibodies reacting with the basement membrane zone, which reacted predominantly with dermal side of 1 M NaCl-split skin. Immunoblotting of the epidermal and dermal extracts with the patient's serum showed no specific reactivity. Further studies are needed to identify the antigenic molecules responsible for the IgM deposition.     

抗β1肾上腺素能受体自身抗体在糖尿病心肌病并高血压发病中的致病机制及临床干预

目的探讨抗G蛋白偶联β1肾上腺素能受体自身抗体致病作用及临床干预。方法以合成的β1受体多肽片段为抗原,应用酶联免疫吸附测定（ELISA）技术,检测171例人血清中抗G蛋白偶联β1受体自身抗体,其中糖尿病心肌病患者71例,2型糖尿病60例及正常对照组40例。对糖尿病心肌病受体自身抗体阳性的为治疗组,阴性的为对照组,两组均在常规强心利尿基础上给予缬沙坦80mg,po,qd;硝酸异山梨醇酯（isosorbide dinitrate）10mg,po,tid;酒石酸美托洛尔（metororolol tartrate）25mg po,bid;双氯噻嗪12.5mgpo,qd;阿斯匹林100mg po,qd,分别观察阳性组和阴性组对心功能的影响,6～12个月采用超声心动图进行对比观察。结果糖尿病心肌病组抗β1受体阳性率为57.7%（41/71）,明显高于糖尿病无心肌病组18.3%（11/60）及正常对照组17.5%（7/40）,比较具有统计学意义（P〈0.01）。阳性组反映左室形态、收缩、舒张功能的指标明显改善（P〈0.05）,阳性组优于阴性组,阳性组总有效率为82.9%,阴性组56.7%。结论免疫学机制可能参与糖尿病心肌病病理生理过程;酒石酸美托洛尔可明显改善心功能。     

放射配基结合抑制分析监测抗β受体抗体应答

通过正交试验改良放射配基(~(125)I-心得静)结合抑制分析(RBIA),所得的最佳实验条件为孵育温度30℃,缓冲液pH7.4,加血清预孵育40min,加~(125)I-PIN孵育20min;用于监测猪心肌细胞膜免疫BALB/c小鼠的抗β受体抗体应答,其血清中抗体对~(125)I-PIN结合β受体的抑制呈浓度依赖性,且为非竞争性抑制。同时还讨论了RBIA对于测定病人体内循环抗β受体自身抗体的临床应用价值。     

Successful therapy of pemphigus vulgaris with immunoadsorption using the TheraSorb™ adsorber

Pemphigus vulgaris (PV) is caused by autoantibodies to desmogleins. Standard immunosuppressive therapy may be limited by concomitant diseases or ineffective.In these cases, removal of circulating antibodies by immunoadsorption can induce remission. An 87‐year‐old woman with PV and considerable co‐morbidities suffered from extensive mucous membrane erosions and bouts of skin blistering refractory to treatment with methotrexate,as well as mycopheno‐late mofetil and corticosteroids even when combined with plasmapheresis and intravenous immunoglobulin. Adjuvant immunoadsorption therapy with the TheraSorb? columns‐first weekly, than monthly‐induced a complete remission, as well as a parallel decrease in PV antibody titers. Continued therapy for 18 months kept the patient in remission but for one infection‐related relapse, and remission has been stable over two further years on low‐dose methotrex‐ate monotherapy. This case confirms the clinical efficacy of immunoad‐sorption in PV and adds another type of adsorber column to the armamentarium, which is useful to the dermatologist who has to cooperate with local lipid apheresis or dialysis units.     

Immunopathology of the Noninfectious Posterior and Intermediate Uveitides

The posterior and intermediate uveitides share an underlying immune etiology; however, they can be clinically and immunopathologically distinguished. Although the initiating stimuli for posterior and intermediate uveities are not known, it is believed that an exogenous agent (such as a bacterium or a virus) or an endogenous molecule may induce disease. In either case, T-helper lymphocytes in conjunction with human leukocyte antigens are likely to be involved. This review examines the epidemiology, histology, immunopathology, and theories of pathogenesis of several posterior and intermediate uveitides, including sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, Beh?et's disease, sarcoidosis, intermediate uveitis, white dot syndromes, and birdshot retinochoroidopathy.     

Characterization of novel platelet and endothelial cell target antigens in a family with genetic susceptibility to autoimmunity.

This report describes a French Canadian family whose members exhibit a high incidence of allo- and autoantibodies to antigens present on both platelets and endothelial cells. This is correlated with various HLA specificities known to be associated with autoimmunity, such as A1, B8, DR3, and, in some cases, with clinical disorders, including nephritis, hypertension, and thrombocytopenia. Immunoblot analysis using platelet and endothelial cell lysates showed serum antibodies to a 75 kDa endothelial cell surface polypeptide and to polypeptides with apparent mass of 115 kDa and 26 kDa found on both platelets and endothelial cells. This 115 kDa internal platelet protein was also found in a variety of other cell types, such as mononuclear cells, and increased following cell activation. Monoclonal antibody immunobilization assays were used to characterize the 26 kDa polypeptide; in three of the four patients tested, an antibody to leukocyte differentiation antigen CD9 was identified. The asymptomatic child of the propositus also exhibited an autoantibody against an 80 kDa platelet protein which was sensitive to thrombin digestion, suggesting that this polypeptide may be platelet glycoprotein V. In addition, P1A1 alloantibody was identified in one sister who had given birth to a severely thrombocytopenic boy and who herself had a severe vascular rejection to a cadaver kidney 2 years prior to this study. The propositus also developed hypertensive renal disease following a pregnancy and became dialysis dependent. Thus, members of this family have developed a variety of antibodies, particularly to platelet and endothelial cell antigens. Some subjects have remained asymptomatic in spite of having autoantibodies. However, others have been seriously ill, and their immune response to these antigens is believed to have played a role in the pathogenesis of their neonatal alloimmune thrombocytopenic purpura, hypertensive renal disease, renal graft rejection, and thrombocytopenia.     

M2抗体重组人源靶抗原二联体在原发性胆汁性肝硬化患者中的检测及应用

目的 利用重组抗原BCOADA-E2和PDC-E2的二联体（BP），检测PBC患者血清中的M2抗体并探讨其临床意义。方法 经Ni—NTA亲和柱纯化重组表达的BP融合蛋白，分别建立免疫印迹法（IBT）和酶链免疫吸附（ELISA）法检测60份PBC患者血清，以60份其他肝病患者、60份自身免疫病患者、80例正常人血清为对照组。结果 经常规试剂盒检测为M2（＋）的60份患者血清，利用重组抗原检测阳性53例，阴性7例，阳性率为88．3％；经常规试剂盒检测为M2（-）的60份自身免疫病患者血清、60份其他肝病患者和80例正常人血清，利用重组抗原检测为M2（-）。结论 利用重组抗原BP检测M2抗体敏感性较高。对临床辅助诊断PBC提供一定的手段。     

原发性高血压患者血清一氧化氮、抗胰岛素自身抗体的变化及意义

目的探讨血清一氧化氮、抗胰岛素自身抗体(IAA)在原发性高血压患者中的变化及意义。方法对45例原发性高血压患者及40例健康对照者进行血清一氧化氮含量及IAA测定,采用硝酸还原酶法检测一氧化氮含量,采用ELISA法检测IAA。结果高血压患者血清一氧化氮水平明显减低,与对照组比较差异有显著性[(71.68±11.72)μmol/L与(81.25±10.56)μmol/L,P<0.01],高血压患者IAA阳性率为33%,较对照组(10%)显著增高(P<0.05)。结论血清一氧化氮水平含量的减低、IAA的产生可能与高血压的发生、发展有关。及早采取干预可能是改善血管内皮功能、减轻胰岛素抵抗状态、促使原发性高血压患者血压恢复的有益措施。