磺脲类降糖药继发失效患者中成人隐匿性自身免疫糖尿病的患病率调查

目的　探讨磺脲类降糖药继发失效 (SF)患者中成人隐匿性自身免疫糖尿病 (LADA)的患病率及其临床特点。　方法　在SF组 (n =2 38)中筛查谷氨酸脱羧酶抗体 (GAD Ab)和胰岛细胞抗体 (ICA) ,并将之与非继发失效 (NSF)组 (n =110 )中的阳性率比较。　结果　SF组中GAD Ab阳性的LADA的患病率为 13.9%( 33 2 38) ,NSF组为 10 .0 %( 11 110 ) ,两组差异无显著意义 (P >0 .0 5 )。LADA患者体重指数低于GAD Ab阴性者 (P <0 .0 1) ,发病年龄、血压、甘油三酯、C肽值均降低 (P <0 .0 5 )。联合检测GAD Ab和ICA ,SF组中LADA的患病率可达 2 2 .7%( 5 4 2 38) ,NSF中为 18.1%( 2 0 110 ) ,SF组与NSF组LADA患病率高于单独以GAD Ab检测 (P <0 .0 1)。　结论　SF的糖尿病患者中LADA的患病率较高。联合检测GAD Ab和ICA可提高LADA诊断的敏感性。     

ABC-ELISA法定量检测红细胞相关抗体及临床应用

目的 :寻求一种温抗体型自身免疫性溶血性贫血 (WAIHA)的诊断方法 ,提高 AIHA的诊断率。方法 :用竞争抑制法原理 ,建立亲和素生物素化酶复合物酶联免疫吸咐测定 (ASC- EL ISA) ,定量检测红细胞相关抗体(EAIg G)。共检测正常人 6 0例 ,WAIHA患者 41例 ,非免疫性溶血性贫血 5 9例。结果 :1正常组 EAIg G值 0 .2 6± 0 .12 fg/ RBC,EAIg G正常上限 0 .5 fg/ RBC(x± 2 s) ;WAIHA组为 2 .85± 1.6 8fg/ RBC,与正常组比较 ,差异极为显著 (P <0 .0 0 1) ;非免疫性贫血组为 0 .5 9± 0 .93fg/ RBC,与正常比较 ,差异不显著性 (P >0 .0 5 )。 2 41例WAIHA患者中 ,37例 Coom bs试验阳性 ,4例 Comm bs试验阴性 ,患者临床表现典型 ,皮质激素治疗反应良好 ,EAIg G值均显著增高 ,可证实为 WAIHA。 3动态观察 EAIg G值 ,随访 10例患者 ,随着病情好转 ,Hb、RBC上升 ,Ret下降 ,EAIg G量减少。结论 :定量检测 EAIg G,可作为 WAIHA的诊断指标之一 ,对 Coombs试验阴性的WAIHA更具有诊断价值 ;EAIg G的动态观察可作为观察疗效和估计预后的指标     

本刊2015年1～6期“重点号”选题

<正>为使作者了解我刊的编辑出版计划,及时地为我刊惠赐稿件,《临床肝胆病杂志》编委会确定了2015年1~6期"重点号"选题:1.中西医结合肝胆胰疾病;2.自身免疫性肝病;3.肝纤维化及肝硬化;4.乙型肝炎;5.胰腺疾病;6.原发性肝癌第6期以后重点号:胆汁淤积和胆道疾病;肝衰竭(顺序暂不分先后)。     

Graves病合并胰岛素自身免疫综合征一例

Graves病临床上常见 ,但Graves病合并胰岛素自身免疫综合征较少见 (IAS) ,现将本院 1例Graves病合并IAS患者报道如下。患者 ,女性 ,43岁 ,因怕热、多汗、心悸、多食、善饥 2年 ,用丙基硫氧嘧啶治疗两周效果不明显于 2 0 0 1年 1月 3 1日入院。体检 :Bp 110 /70mmHg ,右眼裂稍宽 ,右眼球稍突出 ,甲状腺Ⅰ度肿大、弥漫性 ,质韧 ,心肺 ( -) ,肝脾不大。实验室及辅助检查 :T3 7.0mmol/LT42 84mmol/L ,TSH 1.66mlU/L(正常参考值为T3 0 .9～ 2 .2mmol/L ,T45 7～ 12 0mmol/L ,TSH <10mlU /L) ,TGAb 2 8.3 5 % (正常参考值 <3 0 % )、…     

自身免疫性胰腺炎复发合并带状疱疹1例报告

正1病例资料患者男性,62岁,因"间断面黄、目黄7个月"于2018年9月5日入本院。患者入院前7个月无明显诱因出现皮肤黄染,伴间断上腹部胀痛,就诊于吉林大学中日联谊医院,肝功能:AST 46. 75 U/L,ALT 127. 92 U/L,TBil 77. 12μmol/L,DBil34μmol/L,IBil 43. 12μmol/L; IgG4 15. 2 g/L;腹部超声提示:     

自身免疫性溶血性贫血并发妊娠1例

患者女 ,2 3岁。因头昏、乏力、活动后心悸、解酱油色尿 1个月余 ,于 1 999年 6月 1 7日入院。体检 :贫血貌 ,皮肤无出血点 ,巩膜轻度黄染。心肺正常 ,肝未及 ,脾大肋下 2ｃｍ。实验室检查 :血红蛋白 44ｇ/Ｌ ,红细胞1 .1 2× 1 0 1 2 /Ｌ ,白细胞 5 .7× 1 0 9/Ｌ ,核苷 0 .61 ,淋巴细胞 0 .39,血小板 1 63× 1 0 9/Ｌ ,网积红细胞 0 .0 9,红细胞比积 0 .1 44 ;尿常规 :蛋白正常 ,尿胆元 2 .0ＥＵ/ＤＬ。肝功能 :直接胆红素 1 1 .2 7μｍｏｌ/Ｌ ,总胆红素32 .1 1 μｍｏｌ/Ｌ ,总蛋白 70 .35 ｇ/Ｌ ,白蛋白40 .93ｇ/Ｌ ,球蛋白2 9.42ｇ/Ｌ…     

本刊2015年1~6期“重点号”选题

<正>为使作者了解我刊的编辑出版计划,及时地为我刊惠赐稿件,《临床肝胆病杂志》编委会确定了2015年1~6期"重点号"选题:1.中西医结合肝胆胰疾病2.自身免疫性肝病3.肝纤维化及肝硬化4.乙型肝炎5.胰腺疾病6.原发性肝癌第6期以后重点号:胆汁淤积和胆道疾病;肝衰竭(顺序暂不分先后)。为本刊重点号的投稿请注明"***重点号投稿"字样。     

胰岛素对成人隐匿性自身免疫性糖尿病患者血浆瘦素水平的影响

目的　探讨胰岛素对成人隐匿性自身免疫性糖尿病 (LADA)患者血浆瘦素水平 (PLEP)的影响。　方法　以 32名健康者为正常对照 ,用ELISA法测定 32例LADA患者基础血浆胰岛素水平(PINS)和PLEP ,并于胰岛素治疗后第 1、2、3、5、7日和第 12周分别复查空腹PINS和PLEP。　结果　( 1)LADA患者基础PINS和PLEP均显著低于对照组 ,PINS越低 ,PLEP也越低 ,两者呈显著正相关 (r =0 .5 72 ,P <0 .0 1) ;( 2 )胰岛素治疗后 ,在体脂无变化条件下 ,PLEP随PINS的升高而上升 ,两者呈显著正相关 (r=0 .86 8,P <0 .0 5 ) ;( 3)PLEP与体重指数和脂肪百分比呈显著正相关 (P均 <0 .0 5 )。　结论　LADA患者内源性胰岛素缺乏导致低瘦素血症 ,PINS是影响PLEP的主要因素。     

自身免疫性肝炎的动物模型研究

目的 建立实验性自身免疫性肝炎（ＥＡＨ）小鼠模型,并对其进行动态观察。方法 以同种系Ｓ－１００肝抗原与弗氏完全佐剂充分经后两次予小鼠腹腔注射,并设单纯磷酸盐缓冲液（ＰＢＳ）、Ｓ－１０肝抗原和弗氏完全佐剂处理对照组。将Ｓ－１００肝抗原层析分离后观察自身抗原特异性Ｔ细胞增殖反应。结果 且小鼠在首次注射后２周即可见到多形核细胞特别是淋巴细胞的浸润。首次注射后４周组织学改变达高峰,组织学病谱的消退较慢;血     

Experimental autoimmune hepatitis: disease induction, time course and T-cell reactivity

This study describes a murine model of autoimmune hepatitis: experimental autoimmune hepatitis. Experimental autoimmune hepatitis could be induced most effectively in male C57BL/6 mice by intraperitoneal immunization with the 100,000 g supernatant of syngeneic liver homogenate (S-100) in complete Freund's adjuvant. BALB/C and C3H mice were less susceptible than C57BL/6 mice. Experimental autoimmune hepatitis could not be induced in Lewis rats. Intraperitoneal immunization was more effective than intramuscular or subcutaneous injections, and the amount of protein administered above a threshold was of little influence. A single intraperitoneal injection of S-100 in complete Freund's adjuvant resulted in hepatitis of at least 6 mo duration. Histological changes were most marked 4 wk after disease induction. The histological findings were characterized mainly by perivascular inflammatory infiltrates and hepatocyte necroses. The histological changes were accompanied by biochemical evidence of liver cell death. Passive transfer of experimental autoimmune hepatitis with concanavalin A-activated splenocytes was possible. Specific T-cell reactivity against fractions of S-100 could be demonstrated in vitro. Thus experimental autoimmune hepatitis is a murine model of autoimmune hepatitis probably mediated by autoreactive T cells. It will allow studies of the pathogenesis of autoimmune hepatitis.     

白介素-17在自身免疫性肝炎中的作用及其机制研究

目的：探讨IL（白细胞介素）-17在自身免疫性肝炎（autoimmune hepatitis,AIH）患者和AIH小鼠中的作用及其机制。方法：选取AIH患者和健康者各12例,分离其外周血单个核细胞（PBMC）,实时定量PCR方法检测PBMC中IL-17的表达。将S-100肝抗原与弗氏完全佐剂经腹腔注入到C57BL／6小鼠体内而建立AIH小鼠模型,通过尾静脉注入IL-17中和抗体,观察小鼠肝功能变化和肝脏病理组织学变化。结果：与健康者相比,AIH患者PBMC中IL-17的表达明显增高。AIH小鼠模型中,IL-17中和抗体明显地降低了血清中ALT水平,并且减轻了小鼠肝脏炎症反应。结论：IL-17在AIH患者血清中明显升高。采用IL-17中和抗体干预后,其AIH小鼠的肝功能及肝脏损伤明显好转。证实了IL-17在AIH的发病过程中起了极其重要的作用。     

T细胞疫苗对实验性自身免疫性肝炎的影响

目的 观察T细胞疫苗对实验性自身免疫性肝炎(EAH)的影响。 方法 在第1天和第7天分别以新鲜制备的含蛋白质浓度为0.5～2.0 g/L的S-100肝抗原0.5 ml与等体积的弗氏完全佐剂充分乳化后予小鼠腹腔注射,以诱导EAH的产生。T细胞疫苗采用EAH模型小鼠首次免疫后2周的脾脏细胞灭活而成。模型组(6只),在首次免疫前第14天和免疫第7天,每只小鼠腹腔注射磷酸盐缓冲液1 ml;T细胞疫苗组(8只)和无关T细胞疫苗组(6只)在首次免疫前第14天和免疫第7天分别腹腔注射T细胞疫苗和无关T细胞疫苗悬液各1 ml。 结果 T细胞疫苗预防组的肝组织病变严重程度和血清丙氨酸氨基转移酶水平较模型组显著减低,分别为1.44±0.88对2.3 3±0.87,t=2.24,P<0.05和63.0±23.4对115.1±39.6,t=2.37,P<0.01;而无关T细胞疫苗组无显著变化。 结论 T细胞疫苗在小鼠EAH中能有效缓解肝内炎症坏死病变。以无关T细胞用作T细胞疫苗时无效,提示T细胞疫苗具有独特型特异性。     

Genetic bases of autoimmune hepatitis

Our goal was to review the hypotheses in evolution that promise to elucidate the genetic bases of autoimmune hepatitis. DRB1*0301 and DRB1*0401 are the principal risk factors in Britain and the United States. Other susceptibility alleles in different ethnic groups commonly share the same or a similar motif at the critical DR71 position of the HLA class II molecule. Disease severity may be determined by the number of alleles encoding lysine at the DR71 position, the density of dimers presenting antigen, and the avidity of T-cell receptors for the displayed antigen. Concurrence on the same or different chromosomes of other nonspecific autoimmune promoters may also contribute. A negatively charged residue at the P4 position of antigenic peptides is preferred for binding to the disease-susceptibility alleles, and this complex may be recognized by promiscuous T cells. We conclude that autoimmune hepatitis is a model by which to study the genetic bases of autoimmunity.     

Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis： Involvement of nuclear factor kappa B

To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B （NF-KB） were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines （interferon-y, IL-12, IL-1β and TNF-α） were observed.RESULTS： The activity of p38 MAPK and NF-~：B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~：B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.     

自身免疫性肝炎小鼠肝组织神经细胞粘附分子的表达

目的观察实验性自身免疫性肝炎(EAH)肝组织中神经细胞粘附分子(NCAM)的表达,并探讨其表达强度与肝组织学分级的相关性。方法以同种系S-100肝抗原与弗氏完全佐剂充分乳化后于第1和第7天于C57BL/6小鼠腹腔注射诱导EAH模型。分别于首次免疫后第7、14和21天处死小鼠。以免疫组织化学和RT-PCR法研究NCAM表达。结果EAH模型组小鼠肝内NCAM表达逐渐增强,淋巴细胞浸润和肝细胞破坏逐渐加重。强的松龙可改善肝组织学分级,并抑制NCAM的表达。NCAM的表达强度与肝组织学分级呈正相关(r＝0.71,Ｐ＜0.01)。结论NCAM作为移行信号而便于淋巴细胞的肝内浸润,从而诱导肝细胞的损伤。     

A human T-cell clone cytotoxic for hepatocytes from patients with chronic non-A, non-B hepatitis

A human T-cell clone (TA-NB-2) which could lyse hepatocytes from patients with chronic non-A, non-B (NANB) hepatitis was established (Proc Natl Acad Sci USA 1989;86:2883–2887). TA-NB-2 cells belonged to CD3⁺ CD8⁺ cytotoxic T lymphocytes, and recognized the target hepatocytes by T-cell receptor without restriction by major histocompatibility complex (MHC) antigens. TA-NB-2 cells significantly lysed hepatocytes from 22 of 23 patients with chronic NANB hepatitis, whereas they lysed hepatocytes from only one of 17 control patients with chronic type B hepatitis, acute hepatitis B or acute hepatitis A. TA-NB-2 cells also significantly lysed hepatocytes from 4 of 5 patients with autoimmune liver disease. The results suggest that TA-NB-2 cells specifically recognize a NANB hepatitis-related antigen expressed on NANB hepatitis virus-infected hepatocytes by T-cell receptor in non-MHC-restricted manner. The results also suggest that most, if not all, cases of chronic NANB hepatitis are caused by one agent and that a portion of cases of autoimmune liver disease may be induced by infection with a NANB hepatitis virus. The authors are grateful to Sachiyo Terada for her skillful technical assistance. This study was supported in part by a Grant-in-Aid for Cancer Research (63-8) from the Ministry of Health and Welfare, Japan.     

实验性自身免疫性肝炎小鼠的口服耐受诱导研究

口服耐受是一种治疗全身性炎症疾病的潜在手段。在一些动物模型中,口服自身抗原可抑制自身免疫反应。目的:观察在实验性自身免疫性肝炎(EAH)小鼠中诱导口服耐受对肝脏病变的影响。方法:在实验第1天和第7天,将新鲜制备的蛋白质浓度为0.5-2 g/L的肝抗原S-100 0.5 ml和等体积的弗氏完全佐剂(CFA)充分乳化后,予C57BL/6小鼠腹腔注射,以诱导EAH的产生。诱导:EAH前5天起,每天分别予小鼠插管喂饲1 mg和10mg的肝抗原S-100、肝抗原S-100第1峰、第2峰和第3峰,对照组以PBS 1 ml灌胃。结果:仅肝抗原S-100第1峰抗原高剂量组小鼠的肝组织学病变程度较对照组显著减轻(P<0.05),血清丙氨酸转氨酶(ALT)水平也较对照组显著下降(P<0.05)。肝抗原S-100总抗原高剂量组的血清.ALT水平较对照组显著下降(P<0.05),肝组织学病变程度呈下降趋势,但与对照组的差异无显著性。结论:口服肝抗原S-100第1峰抗原可诱导EAH小鼠的免疫耐受。     

Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other chronic liver diseases

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20% ), and in 5 out of 9 with multiple myeloma (56% ). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibodypositive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV -related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma. This study was supported by the Ministry of Health, Science and Welfare of Japan.