A Follow-up Study of 68 Patients with Anti-mitochondrial Antibodies (AMA)

ABSTRACT During the period 1976-83, anti-mitochondrial antibodies (AMA) were detected in 68 patients out of about 48 000 sera (0.14%) analyzed for a repertoire of autoantibodies at the Department of Immunology, University Hospital of Tromsø. Fifty-five of these patients were women, and only 10 had unequivocal primary biliary cirrhosis (PBC). At follow-up in 1984, 48 out of these 68 patients were accessible for complementary testing. The AMA test became negative in 17 of these 48 patients during the observation period. Eleven of these 17 had originally a titer of 50. Seven of the 31 patients with persistent AMA were without detectable liver pathology. One patient had antibodies against smooth muscle, one against cell nucleus, whereas 35 had an increased serum IgM level. In conclusion, most patients with AMA do not have obvious PBC, a low AMA titer is likely to be transient, and there is a strong association between AMA and an increased serum IgM level.     

Prevalence of immune disturbances and chronic liver disease in family members of patients with primary biliary cirrhosis

BACKGROUND AND AIMS: Primary biliary cirrhosis (PBC) has been reported in up to 4-6% of first degree relatives of patients with the disease. In addition, immune abnormalities, including hypergammaglobulinemia, autoantibodies and increased frequency of autoimmune disorders, were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of PBC in relatives of patients with PBC, and to investigate the occurrence of chronic liver disease (CLD) and immune abnormalities in these subjects. METHODS: One-hundred first degree relatives of 26 patients with PBC were interviewed and submitted to physical examination and determination of liver enzymes, gamma-globulin, bilirubin and auto-antibodies, including antinuclear (ANA), antismooth muscle (SMA), antimitochondrial antibodies (AMA) by indirect immunofluorescence (IIF) and anti-M2 antibody by immunoblotting (IB). RESULTS: Immune disturbances were rarely observed in relatives of PBC patients. Higher gamma-globulin levels, SMA and ANA were detected in four, eight and two family members, respectively. In most subjects, these autoantibodies were either in low titers or associated with concurrent diseases. Only four relatives had extrahepatic autoimmune diseases and another eight exhibited other CLD. Primary biliary cirrhosis was detected in a sister of one patient. Additionally, two other relatives of PBC patients who tested negative for AMA by IIF showed reactivity for anti-M2 by IB. CONCLUSIONS: Immune disturbances, including ANA and SMA, are uncommon in family members of PBC patients. Conversely, anti-M2 antibodies and overt PBC do occur in relatives of PBC patients, even in Brazil where the disease is quite rare.     

甲亢患者~(131)Ⅰ治疗前血清TGAb和TPOAb含量与早发甲减关系的探讨

目的:测定放射性~(131)Ⅰ治疗前甲亢患者血清甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TGAb)水平,探讨其在~(131)Ⅰ治疗后与早发甲减发生的关系。方法:根据~(131)Ⅰ治疗前TPOAb、TGAb的检测结果,将165例患者分成3组:双阴组10例,单阳组26例,双阳组129例,比较各组间早发甲减的发生率;再将双阳组的129例患者,按TPOAb、TGAb滴度水平的高低分成3组:A组66例,B组54例,C组9例,进一步探讨~(131)Ⅰ治疗前TPOAb、TGAb滴度水平的高低与早发甲减的关系。结果:~(131)Ⅰ治疗后的165例患者,各组间早发甲减发生率差异无统计学意义(χ2=1.35,P>0.05)。双阳组的129例患者,按TPOAb、TGAb滴度水平高低分成3组,各组间早发甲减发生率差异无统计学意义(χ2=0.89,P>0.05)。结论:TGAb、TPOAb滴度水平的高低,对于甲亢~(131)Ⅰ治疗后早发甲减的预测参考价值不大。     

An unusual case of recurrent hypoglycaemia: 10-year follow up of a child with insulin auto-immunity

We report the case of a child with hypoglycaemia due to insulin auto-immunity. Insulin autoimmunity is the third most frequent cause of hypoglycaemia in Japan where the first cases were described. The child has been followed for the past 10 years with recurrence of hypoglycaemic symptoms and high titres of insulin antibodies.     

Increased negative selection impairs neonatal B cell repertoire but does not directly lead to generation of disease-associated IgM auto-antibodies

To determine if increased negative B cell selection, due to lowered signaling threshold of responsiveness to a ligand as a result of SHP-1 deficiency, during ontogeny leads to the origin of disease-associated IgM auto-antibodies (AAbs), 47 V(H)J558+ VDJCmu rearrangements from SHP-1-deficient viable motheaten (me(v)/me(v)) and 24 J558+ VDJCmu rearrangements from normal me(v)/+ neonatal (<24 h post-birth) B cells were examined for their structural properties. None of the J558+ VDJCmu rearrangements from autoimmune-prone me(v)/me(v) had the characteristic CDR3H size restriction or arginine residues noted in disease-associated IgM AAbs. However, the MVAR2/10 genes are expressed at a high frequency in me(v)/me(v) (31.9%) as compared with me(v)/+ (16.7%), and pM11 gene expression is exclusively (14.9%) noted in me(v)/me(v) B cells. Clearly, there is a trend toward higher expression of pM11 genes (P-value < or = 0.09) in autoimmune-prone me(v)/me(v) strain. The CDR2H region of J558+ VDJCmu recombinations from me(v)/me(v) has increased hotspot triplets predisposing to mutations as compared with me(v)/+ (P-value < or = 0.01) mice. A higher DFL D-gene expression is noted in J558+ VDJCmu rearrangements from me(v)/me(v) (P-value < or = 0.1) in contrast to me(v)/+. The sophisticated logistic regression and odds ratio analysis of V-, D- and J-gene expressions in neonatal B cells from me(v)/me(v) and me(v)/+ mice demonstrates differential composition of the germ line IgM repertoire as a result of SHP-1 deficiency. These observations suggest that increased negative B cell selection during ontogeny impairs the developing IgM antibody repertoire but does not directly lead to generation of disease-associated IgM AAbs.     

抗心肌肌凝蛋白重链自身抗体IgG亚类对腹主动脉缩窄术后大鼠左室功能的影响

[目的]探讨抗心肌肌凝蛋白重链自身抗体(AMCHA)IgG亚类的产生与腹主动脉缩窄术后大鼠左室功能的关系。[方法]应用腹主动脉缩窄术建立慢性心力衰竭(CHF)大鼠模型,测定血流动力学变化,计算左心室重量/体重(LVW/BW)比值;以合成的大鼠心肌肌凝蛋白重链部分肽段(1135-1150氨基酸残基)为包被抗原,采用间接ELISA方法检测大鼠血清中心肌肌凝蛋白重链自身抗体(MCHA)IgG亚类的水平及动态变化。[结果]CHF大鼠手术组与假手术组相比左室压力上升和下降最大速率降低(+dp/dtm ax:2103.91±606.89 vs 3196.64±383.29;-dp/dtm ax:-1709.60±460.96 vs-2762.64±514.42,P<0.01),左室舒张末压升高(LVEDP:17.49±8.33 vs-5.69±1.19,P<0.01)、左室收缩压升高(LVSP:131.67±25.14 vs 111.98±4.63,P<0.05)、左心室重量/体重比值升高(LVW/BW:3.04±0.44 vs 2.57±0.20,P<0.01),术后1~2周,IgG1、IgG2 a和IgG2b自身抗体...     

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study

Objectives: Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort.

Methods: One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed.

Results: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p?auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r?=??.143, p?=?.047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207?ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207?ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39–8.28) versus 3.95 (1.78–7.0), p?=?.03; 168.84?±?153.63 versus 101.44?±?47.36, p?=?.01; 34.1% (14/41) versus 0% (0/9), p?=?.04; respectively).

Conclusion: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.     

甲状腺自身抗体对131I治疗青少年Graves病后甲减的影响

研究青少年Graves病(GD)患者治疗前促甲状腺激素受体抗体(TRAb)和甲状腺过氧化物酶抗体(TPOAb)水平对131I治疗后甲状腺功能减退症(甲减)发生率的影响.131I治疗青少年GD患者 264例,治疗前依TRAb和TPOAb分为TRAb阳性、阴性组及TPOAb强阳性、阳性和阴性组;依两抗体不同阳性组合分为A[...     

Pristane诱导小鼠系统性红班狼疮动物模型的研究

目的:建立pristane诱导的系统性红斑狼疮(SLE)小鼠模型,并对该小鼠模型的发病机制进行初步的探讨。方法:6-8周龄雌性BALB/c小鼠单次腹腔注射pristane0.5mL,对照组单次腹腔注射PBS0.5mL,注射前及注射后每2周行流式细胞术(FCM)检测外周血中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例及细胞活化状态B220+Aβ1dhigh),ELISA检测血清中自身抗体(anti-dsDNA,anti-smRNP,anti-ribosomalP0)的含量。至6个月处死动物,FCM检测腹腔细胞中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例和脾脏中细胞的活化(B220,Aβ1d),采用直接免疫荧光法标记小鼠肾脏免疫球蛋白复合物及H&E染色评估小鼠肾脏免疫复合物的沉积及损伤情况。结果:小鼠腹腔注射pristane第2个月开始血清总IgG升高,第3个月起出现自身抗体阳性,到个6月时达到最高,并维持高水平至被处死;Pristane处理6个月后,Pristane处理组小鼠出现关节炎症状,肾脏免疫复合物的大量沉积和明显肾脏损伤。Pristane注射2周起,小鼠外周血中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例明显高于PBS注射组,小鼠腹腔细胞中IFN-α分泌细胞的比例也明显升高;同时外周血和脾细胞中B细胞表面MHCII分子Aβ1d的平均荧光强度(MFI)均高于对照组,表明pristane处理组小鼠中B细胞发生了显著活化。结论:BALB/c小鼠腹腔注射pristane可诱导构建小鼠SLE模型,其SLE的发病可能与IFN-α的持续分泌导致B细胞的异常活化有关。该模型的建立为进一步研究SLE的发病机制提供了良好的动物模型。