丙硫氧嘧啶引起抗中性粒细胞胞浆抗体相关小血管炎6例临床分析

目的：提高临床对丙硫氧嘧啶（PTU）引起抗中性粒细胞胞浆抗体（ANCA）相关小血管炎的认识。方法：分析近年诊治的6例PTU引起ANCA相关小血管炎患者的临床表现、实验室及病理检查、治疗及随访情况。结果：6例患者服用PTU至出现小血管炎症状的时间不等，2月-7年，小血管炎表现也可在PTU停药后出现，临床表现不一，轻者仅皮肤、关节、肌肉受累，重者可出现重度贫血、肺出血、肾受累，抗MPO-ANCA均阳性。停用PTU及激素、免疫抑制剂治疗后病情好转，ANCA滴度下降或转阴。结论：PTU可引起ANCA相关小血管炎，部分可引起肺出血及肾损害，临床应予重视，及时停用PTU及相应治疗大多预后较好。     

原发性小血管炎中ANCA IgG亚型的分布及临床意义

抗中性粒细胞胞浆抗体 (antineutrophilcytoplas micantibody ,ANCA)是一种以中性粒细胞和单核细胞胞浆成分为靶抗原的自身抗体 ,主要为IgG型。通过间接免疫荧光法可将ANCA分为两型 :胞浆型AN CA(cytoplasmicANCA ,c ANCA)与环核型ANCA (peri nuclearANCA ,p ANCA) 〔1〕 。到目前为止 ,已有多种中性粒细胞胞浆成分被证实为ANCA的靶抗原 ,其中最为重要的是髓过氧化物酶 (myeloperoxidase ,MPO)和蛋白酶 3(proteinase 3,PR3)。ANCA可在许多原发性小血管炎患者的血清中检测到 ,如韦格纳肉芽肿(Wegener′sgranulomatosis ,…     

人生长激素的生物素—新和素放大酶联免疫法的建立

为建立有生物素和亲和素放大系统的人血清生长激素 (hGH)酶联免疫分析法 (BA ELISA) ,以微量的GH抗原免疫BALB/C小鼠 ,利用杂交瘤技术制备出 2 9株分泌抗hGH单克隆抗体 (MCA)的杂交瘤株。选择最佳配对MCA ,利用亲和素与生物素高亲和力的特性 ,建立了血清hGH双位点的BA ELISA法。我们的MCA滴度为 (0 5～ 5 0 0 )× 10 4,亲和常数Ka =(0 13～ 1 40 )× 10 10 L/mol。血清hGH的ELISA的灵敏度为 0 0 4± 0 0 1μg/L ;在血清中分别加入 1,2 5 ,5 μg/L的hGH ,其回收率为 90 7%～ 10 7 6 % (平均为 10 1 2 0 %± 0 0 3 % ) ;hGH含量为 2 8、10 0、2 9 8μg/L的血清批内、批间变异系数分别为 4 9%、3 8%、7 9%和 6 2 %、3 5 %、9 5 % ;用本法测定了正常儿童、生长激素缺乏症 (GHD)患儿和活动性肢端肥大症患者空腹血清hGH水平 ,分别为 1 87± 3 0、0 30± 0 42和 8 71± 6 95 μg/L。上述结果表明 ,本ELISA方法灵敏、特异、稳定、准确 ,能确切反映hGH分泌功能 ,在诸多方面均优于RIA。     

T细胞亚群与ANCA相关性小血管炎研究进展

抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AAV)是一种以全身多系统小血管炎症和纤维素样坏死为主要特征的自身免疫性疾病。ANCA作为自身抗体,分别针对蛋白酶-3(PR3)和髓过氧化物酶(MPO)两种靶抗原在AAV过程中起重要作用。T细胞亚群与ANCA有较多参与和相互作用,也是AAV的关键致病因子,但其作用的具体机制尚不完全清楚。本文综述部分T细胞亚群与AAV的研究进展。     

丙基硫氧嘧啶引起抗中性粒细胞胞质抗体相关小血管炎并非药物性狼疮

目的 检测药物性狼疮（DIL）的血清学标志抗组蛋白抗体在抗中性粒细胞胞质抗体（ANCA）阳性的甲亢患者中的阳性率,并探讨丙基硫氧嘧啶（PITU）引起的ANCA相关小血管炎与DIL的关系。方法 以34例ANCA阳性的原发甲亢患者为研究对象,其中18例确诊为PITU引起的ANCA相关小血管炎;同时选取10例原发性ANCA相关小血管炎患者及10例初发未治疗的甲亢患者为对照,应用ELISA法检测抗组蛋白抗体。将我院确诊的PITU引起的ANCA相关小血管炎患者的临床资料与文献中抗甲状腺药物引起的DIL相比较。结果 所有原发性ANCA相关小血管炎的患者及初发未治疗的甲亢患者均未检测到抗组蛋白抗体;在34例PITU引起的ANCA阳性患者中仅1例（2．9％）抗组蛋白抗体阳性,此例患者为18例有血管炎临床表现中的1例（5．6％）。PITU引起的ANCA相关小血管炎不同于DIL,寡免疫复合物的坏死性新月体性肾炎及肺出血为前者的特征性表现。结论 PITU引起的ANCA相关小血管炎患者中抗组蛋白抗体的低发生率提示其与DIL可能不完全相同。     

猕猴黄体生成素放射免疫分析方法的建立

目的 :在生殖医学的动物实验中 ,需要检测猕猴血清中黄体生成素 (MLH)的含量 ,为此建立了猕猴血清黄体生成素 (MLH)的放射免疫分析方法。方法 :用氯胺T法制备12 5I-MLH ,兔抗MLH为第一抗体 ,羊抗兔IgG为分离剂 ,采用液相竞争法建立放射免疫分析方法。结果 :标记抗原比放射性为 6 7μg/mCi,抗体亲和常数为Ka=3 5 5× 10 -9mol/L ,标准曲线形态良好 ,r=0 991,批内误差CV =3 49% ,批间误差CV =4 6 5 % ,最小可测浓度为 0 42 μg/ml,30例正常猕猴血清检测结果为 1 17± 0 6 75 μg/ml。 结论 :MLHRIA的建立对避孕药和性生理药品的动物监测及医学研究均有重要意义。     

一组抗肿瘤单克隆抗体相对亲和常数的测定

本文用ABC-ELISA夹心法测定的终点浓度值分析了一组15种抗人结肠癌McAbs的相对亲和常数。结果是各McAb的相对亲和力各有不同,最高达4.15×10~(-12),最低为6.25×10~(-10)。实验表明本法用于针对复杂而微量的肿瘤抗原的测定是可行的,而且本法可一次测定多个这样的McAbs的相对亲和常数。亦不需标记被测抗体或抗原。故方法简便;且灵敏度高,重复性好,这对有关的研究具有参考价值。     

抗人类白细胞抗原抗体与抗内皮细胞抗体在肾移植慢性排斥反应中作用的相关性

目的 选择发生慢性排斥反应的肾移植患者,根据人类白细胞抗原(human leukocyte anti-gen,HLA)抗体阳性或抗内皮细胞抗体阳性以及两抗体同时阳性进行分组,并同时检测各组患者的血清中肌酐含量作为判断肾功能的指标.探讨在肾移植慢性排斥反应中抗内皮细胞抗体与抗HLA抗体作用的相关性.方法 抗内皮细胞抗体的检测方法用免疫荧光法,抗HLA抗体应用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA),肌酐检测应用的是生化分析仪.结果 移植后处于慢性排斥期抗HLA抗体阳性的患者血清肌酐含量均值为(116.3±5.6)μmol/L,抗内皮细胞抗体阳性的患者血清肌酐含量均值为(114.6±4.7)μmol/L;抗HLA抗体与抗内皮细胞抗体同时阳性的血清标本肌酐含量的中位数是131.2μmol/L,四分位间距为13.6μmol/L;两组间肌酐含量差异有统计学意义(P=0.000).结论 抗内皮细胞抗体和抗HLA抗体均可影响肾移植慢性排斥反应期的肾功能;抗内皮细胞抗体与抗HLA抗体在肾移植慢性排斥期间同时产生,肾功能损害加重.     

抗重组人白细胞介素18单克隆抗体的制备与特性研究

目的 :获得有生物活性的小鼠抗重组人白细胞介素 18(rhIL 18)单克隆抗体。方法 :采用重组hIL 18免疫BALB C小鼠 ,应用杂交瘤技术 ,ELISA法筛选阳性杂交瘤细胞株并经多次克隆化。结果 :建立了 2株小鼠抗hIL 18单克隆抗体杂交瘤细胞 1C7和 1F5 ,染色体数目分别为 92条和 90条 ,所分泌的抗体分别为IgG2a和IgG1,轻链均为κ型 ,腹水IgG抗体经亲和层析法纯化后纯度达 95 %以上 ,效价为 1× 10 - 4和 1× 10 - 5,Westernblot显示 2株单抗均能特异性识别 18 3kD处的rhIL 18蛋白。 1C7单抗的亲和常数Ka=1 7× 10 5,1F5的亲和常数Ka=1 3× 10 5。 2株单抗识别不同抗原表位。结论 :制备的 2株单抗为进一步研究IL 18的分子结构、生物学功能及其与免疫相关性疾病的关系提供了实验材料。     

类风湿性血管炎患者抗内皮细胞抗体的检测和临床意义

类风湿性血管炎 (ＲＶ )作为类风湿性关节炎 (ＲＡ)全身表现的一种 ,其出现常预示病情的严重性。为探讨抗内皮细胞抗体 (ＡＥＣＡ )在ＲＶ中的致病作用 ,本文利用培养的人脐静脉内皮细胞作抗原 ,采用ＥＬＩＳＡ方法检测了 2 1例ＲＶ ,3 0例无关节外表现的ＲＡ患者和 2 6例正常人血清中ＡＥＣＡ ,并作临床意义分析。1　材料和方法1 1　病例选择　临床确诊的 2 1例ＲＶ及 3 0例ＲＡ成年患者并经血清学和组织病理学检查明确排除ＳＬＥ等其他风湿性疾病 ,2 1例ＲＶ患者均经皮肤活检证实。正常对照组为 2 6例健康体检者。1 2　内皮细胞分离、培养…     

强迫症患者与精神分裂症患者的执行功能

目的:比较强迫症和精神分裂症患者执行功能损害的特点。方法:本研究为横断面研究。研究对象为符合中国精神障碍分类与诊断标准第3版诊断标准的强迫症(n=29)和精神分裂症门诊患者(n=30),以及年龄和教育程度匹配的正常对照(n=30)。所有被试接受威斯康星卡片、连线测验、河内塔测验、言语流畅性测验等神经心理学测验评定执行功能。结果:威斯康星卡片测验中,强迫症患者总操作时间短于精神分裂症患者(P0.05),与正常对照接近(P0.05);完成归类数目多于精神分裂症患者(P0.05),与正常对照接近(P0.05);错误应答数目少于精神分裂症患者(P0.05),与正常对照接近(P0.05);完成第一分类所需的应答需要的卡片数目多于精神分裂症患者和正常对照(P0.05)。连线测验中,强迫症患者在连线B的时间和错误数少于精神分裂症患者(均P0.05),与正常对照接近(P0.05)。河内塔测试中,强迫症患者的移动次数和出错次数与精神分裂症患者差异无统计学意义(均P0.05),但多于正常对照(均P0.05)。结论:强迫症总体执行功能水平比精神分裂症水平高,但是概念理解能力差。     

Cerebrovascular accidents differ between patients with atrial flutter and patients with atrial fibrillation

IntroductionFew studies have explored the potential impact of atrial flutter (AFl) on ischaemic stroke (IS) outcome. The aim of the present study was to compare the clinical course of IS in patients with AFl and patients with atrial fibrillation (AF).Material and methodsA retrospective analysis of patients consecutively admitted to a tertiary care centre between 2013 and 2015 due to IS or transient ischaemic attack with permanent AFl or permanent or persistent AF was performed.ResultsThe study groups consisted of 528 patients, including 490 (92.8%) patients with AF and 38 (7.2%) patients with AFl. The mean age and prestroke CHA2DS2-VASc scores were similar between the patients with AFl and those with AF. Most IS cases in the AF group were classified as cardioembolic strokes (74.9% vs. 39.5% in AFl, p < 0.01), and lacunar strokes were the most common in the AFl group (47.4% vs. 14.3% in AF, p < 0.01). The multivariable analysis revealed that the presence of AF (OR = 8.6, 95% CI: 1.2–57, p = 0.02), lacunar stroke (OR = 0.1, 95% CI: 0.03–0.31, p < 0.001), baseline Rankin scale score (OR = 16.6, 95% CI: 9.8–28), lack of prestroke therapeutic anticoagulation (OR = 6.1, 95% CI: 1.1–33), diabetes (OR = 2.9, 95% CI: 1.3–6.5, p < 0.01), chronic heart failure (OR = 14.2, 95% CI: 5.8–34, p < 0.001), and current smoking (OR = 0.92, 95% CI: 0.39–0.99, p < 0.01) were significantly associated with the stroke outcome.ConclusionsDisabling or fatal IS was observed less often in patients with AFl than in patients with AF. This finding can possibly be explained by the more frequent occurrence of lacunar strokes in the AFl group compared with that in the AF group.     

Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy.

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.     

Lipid composition of sputum from patients with asthma and patients with cystic fibrosis

Lipids from the sputum of patients with asthma and with cystic flbrosis were isolated and characterized. In both cases, lipids constituted approximately 30% of the dry material. Phosphatidylcholine was the most abundant lipid. Significant amounts of phosphatidylethanolamine and phosphatidylglycerol were present. Hexosyl ceramides, sphingomyelin, phosphatidylinositol, lysophosphatidylcholine, and lysophosphatidylethanolamine were present as minor lipid components. Appreciable quantities of neutral lipids were present, of which triglycerides and cholesterol were the main constituents. Phosphatidylcholine, sphingomyelin, and phosphatidylglycerol were highly saturated. Large amounts of phosphatidylcholine containing mostly palmitic acid, particularly in the asthmatic sputum, suggests that this highly saturated phospholipid is synthesized in the upper airways for reasons other than its beneficial surface-active properties in the alveoli.     

Intravenous immunoglobulin in patients with anti-GAD antibody-associated neurological diseases and patients with inflammatory myopathies

Controlled trials with intravenous immunoglobulin (IVIg) were conducted in patients with Stiff-Person Syndrome (SPS) and dermatomyositis (DM), two humorally mediated neurological disorders, and in inclusion body myositis (IBM), a T-cell-mediated inflammatory myopathy. The clinical efficacy was compared with alterations on tissue expression of complement, cytokines, chemokines, adhesion molecules, and immunoregulatory genes. The following patients were randomized in three separate trials to receive IVIg or placebo for 3 mo: (a) 16 patients with anti-GAD antibody-positive SPS; (b) 15 patients with DM resistant to therapies; and (c) 19 patients with IBM. After a washout, they crossed to the alternative therapy for another 3 mo. Efficacy was based on the difference in the respective disease scores from baseline to the second and third month of the infusions. In patients with SPS and DM, the scores changed positively and significantly from months 1 through 3, but returned to baseline when the patients crossed to placebo. In contrast, the scores in the placebo-randomized group remained constant or worsened from months 1 to 3, but improved significantly after crossing to IVIg. The muscle scores of patients with IBM did not significantly change between IVIg or placebo. In SPS, the anti-GAD₆₅ antibody titers declined after IVIg but not after placebo. In DM, there was reduction of complement consumption, interception of membranolytic attack complex formation, downregulation of inflammation, fibrosis, cytokines, chemokines and adhesion molecules, and alterations in thousands of immunoregulatory genes. We conclude that IVIg is a safe and effective therapy for patients with SPS and DM unresponsive to other agents. In tissues, IVIg restores tissue cytoarchitecture by suppressing the inflammatory mediators at the protein, mRNA, and gene level.     

Osteonecrosis in patients with SLE

Osteonecrosis is a clinical entity characterized by death of bone marrow and trabecular bone as a result of disruption of blood supply to the bone (1,2). Other aspects of this condition include avascular necrosis, aseptic necrosis, and osseous ischemic necrosis of bones. Osteonecrosis is classified into two main forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis usually develops as a result of traumatic displacement of bone fragments, which leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis of the femoral head is common following fracture of the femoral neck. A variety of systemic diseases and clinical conditions are associated with nontraumatic osteonecrosis. These include autoimmune rheumatic diseases, alcoholism, pregnancy, Gaucher's disease, thrombophilia, corticosteroid therapy, Sickle-cell anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and others. Idiopathic forms of osteonecrosis have also been reported (2–4). Among the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and systemic vasculitis (8). This article reviews the causes, clinical and epidemiological features, diagnosis, and treatment options for osteonecrosis among patients with SLE.