自身免疫性肝炎临床研究现状

自身免疫性肝炎(autoimmune hepatms，AIH)是特异性自身抗原表达或细胞、细胞浆等非特异性自身抗原表达引起自身肝组织损伤的特殊类型的慢性肝炎，血清学显示高丙种球蛋白和自身抗体。AIH是一多器官受累的疾病，发病率世界各地不同，在北美和西欧的白种人AIH发病是慢性肝炎的20％，我国是慢性肝炎住院患者的0．56％。AIH通常分3型。无论男、女、     

抗去唾液酸糖蛋白受体酶联免疫检测法的建立及临床初评

目的 建立肝脏特异性自身抗体的ELISA检测方法，辅助自身免疫性肝炎的诊断。方法 利用亲和层析法从人肝脏组织中直接纯化去唾液酸糖蛋白受体(ASGPR)，经免疫学鉴定后以此纯化抗原包被微孔板，酶联免疫固相吸附试验检测去ASGPR的自身抗体(抗-ASGPR)。结果 本研究从10g肝组织纯化ASGPR，总量为1．6mg。经SDS-PAGE和Dot-ELISA验证，纯化ASCGPR纯度高、具有抗原活性。ASGPR预吸附可阻断血清抗体与ASGPR间的免疫反应，类风湿因子、梅毒阳性血清不干扰本ELISA法的抗原抗体反应。33例自身免疫性肝炎(AIH)患者中检出抗-ASGPR24例，阳性率为72．7％。在临床上高度怀疑AIH的10例患者中，抗-ASGPR阳性者有7例。原发性胆汁性肝硬化、病毒性肝炎、肝炎后肝硬化、肝癌、胆囊炎患者中阳性检出率分别为21．4％(9／42)、16．8％(16／95)、16．1％(10／62)、10．7％(3／28)、14．3％(1／7)。药物性肝炎、酒精性肝炎、系统性红斑狼疮和类风湿性关节炎患者中未检测到抗-ASGPR。200名健康体检者阳性率为4．6％。抗-ASGPR检测对AIH诊断的特异性为89．6％。结论 本研究所建立的抗-ASGPR ELISA检测方法可靠、特异性好。抗-ASGPR检测有助于AIH的诊断，尤其是对那些抗核抗体、平滑肌抗体、肝肾微粒体-1型抗体等自身抗体均阴性、临床高度怀疑AIH病例的诊断可能更为有用。     

自身免疫性肝炎发病机制的研究进展

自身免疫性肝炎（AIH）是一类病因不明的肝脏慢性炎症疾病，典型表现为界面性肝炎、多克隆高7球蛋白血症及诊断特异性肝脏自身抗体，如未予有效治疗，可因持续性坏死性炎症导致肝纤维化和肝硬化。AIH可发生于各年龄段及各种族，女性比男性更易患病。根据血清学标志物AIH可分为两型，1型约占80％，以ANA、抗SMA为主要血清学特征；     

抗微生物药物诱导自身免疫性肝炎的汇总分析

自身免疫性肝炎(autoimmune hepatitis,AIH)是由异常的自身免疫反应介导的肝实质炎性反应性病变.一般认为是存在遗传易感性的个体在环境因素作用下激活针对肝脏抗原的特异性免疫应答反应.近年来,有报道多种药物如抗微生物药物、调脂药和干扰素等亦可引起AIH,即药物诱导的自身免疫性肝炎(drug-induced autoimmunehepatitis,DAIH),占AIH的比例目前尚不确定,约为9％[1],若包含误诊的病例,比例可能更高.由于DAIH起病较为隐匿,如认识不足常会延误诊治.本研究主要汇总分析国内外抗微生物药物诱导AIH的临床特点,为全面认识该病提供依据.     

病毒性肝炎—总论

自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征患者的临床特点——曾珍等(北京解放军第302医院感染三科100039)《中华肝脏病杂志》2005，13(1)：3-5[了解自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)重叠综合征的临床特点。方法：对129例自身免疫性肝病患者的临床资料进行回顾分析，按国际评分标准，诊断AIH／PBC重叠综合征，并将其生物化学、自身抗体、肝穿刺结果与单纯的AIH、PBC患者病例资料比较。结果：129例自身免疫性肝病患者中35例为AIH／PBC重叠综合征患者，占27．1％，以女性患者为主，男女比例为l：10，平均年龄(50．79&;#177;11．27)岁，其实验室检查具有AIH患者的特点，     

自身免疫性肝炎的特异性T淋巴细胞免疫

自身免疫性肝炎(AIH)是一种器官特异性自身免疫性疾病,以肝组织内T淋巴细胞浸润、高Y球蛋白血症、血清自身抗体阳性、具有人类白细胞抗原(HLA)遗传背景、常伴发其他自身免疫性疾病和对免疫抑制治疗有效为特征[1].自身免疫反应介导的肝细胞损伤是AIH发病机制之一,且遗传因素也参与了AIH的发病,而在AIH免疫发病机制方面,自身反应性T淋巴细胞,尤其是AIH靶抗原特异性T淋巴细胞起至关重要的作用,但具体机制尚未阐明. 一、AIH特异性靶抗原的认识 自身抗原是自身抗体和自身反应性T淋巴细胞作用的靶点,是自身免疫反应的基础.自身抗原必须满足4个条件:(1)必须存在一个相应的高滴度器官特异性自身抗体;(2)需证实T淋巴细胞对相对应的抗原致敏;(3)存在疾病特异性的B淋巴细胞和T淋巴细胞表位;(4)需有抗体和(或)自身反应性T淋巴细胞致病的证据.     

应用噬菌体展示技术初步筛选自身免疫性肝炎患者肝细胞靶抗原

自身免疫性肝炎（AIH）是以肝脏炎症反应为主的自身免性肝病．病因不明，其中Ⅰ型AIH最为常见，但尚未发现其存在于肝细胞的自身靶抗原．本研究利用Ⅰ型AIH患暂血清作为固相靶分子，用噬菌体展示的肝细胞cDNA筛选存在于肝细胞的自身靶抗原。     

自身免疫性肝炎

1965年Makay提出了自身免疫性肝炎(Autoimmune hepatitis,AIH)的概念,即遗传、药物和营养障碍等因素对肝脏的损害,改变了自身抗原性,刺激免疫系统产生抗体,抗原抗体反应导致肝脏持续性慢性活动性炎性损害,也曾称为狼疮样肝炎和浆细胞肝炎。据调查在美国AIH约占慢性肝病的10～15％。 一、AIH患者血清中的自身抗体及其分型     

自身抗体谱测定在自身免疫性肝炎临床诊断中的应用

自身免疫性肝炎（AIH）是以肝细胞为靶抗原引起的自身免疫性疾病，也是一种病因不明，以肝脏门静脉周围病变为主的慢性炎症病变，同时外周血中常存在各种自身抗体及高球蛋白血症。主要影响女性，其临床表现是非特异的，AIH的诊断是在综合临床表现、血清学和免疫学的AIH特征性指标，并除外其他引起肝病的原因之后得出，若不经治疗，预后较差。我们对31例AIH患者及75例非AIH患者进行了自身抗体谱检测。     

熊去氧胆酸与自身免疫性肝炎

自身免疫性肝炎(autoimmune hepatitis,AIH)是机体免疫系统对自身肝细胞抗原失耐受,产生自身抗体及自身反应性T细胞所致的一种急、慢性肝病。在欧美国家有较高的发病率,约占慢性肝炎的10％～20％;在嗜肝病毒流行的亚、非地区约占慢性肝炎的5％;我国目前尚缺乏该病人群发病率资料,有关报道日渐增多。AIH的首选治疗是用免疫抑制剂,近年来随着对熊去氧胆酸(ursodeoxycholic acid,UDCA)作用机制的深入研究,发现UDCA可有效或辅助治疗AIH,引起广大学者的兴趣。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.