Evaluation of the Crithidia assay to distinguish between auto-immune chronic active hepatitis and systemic lupus erythematosus

The aim of this study was to determine if the Crithidia luciliae assay for auto-antibodies to double-stranded DNA, often positive in systemic lupus erythematosus, is always negative in auto-immune chronic active hepatitis (CAH) as has recently been suggested. Twenty-five patients were identified as having auto-immune CAH. Mean duration of follow-up was 10.5 years. Antinuclear antibodies were detected in 92%, smooth muscle antibodies in 76% and antimitochondrial antibodies in 16%. Antibodies to double-stranded DNA were detected by the Crithidia assay in four patients (16%). Two of these patients had positive tests on only one occasion and no features of systemic lupus erythematosus. In the other two the assay was persistently positive. During follow-up both developed arthritis and serositis but the liver lesion remained the dominant clinical feature. It was concluded that there is significant serological overlap between auto-immune CAH and systemic lupus erythematosus making the Crithidia assay unreliable in distinguishing between them.     

The enigma of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease characterized by a striking predominance in female patients (with most cases diagnosed between ages 40 and 60 yr) as well as serum auto-antibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and, ultimately, liver cirrhosis and failure (1). The precise mechanisms leading to selective destruction of biliary epithelial cells lining intrahepatic bile ducts are still unknown, although numerous immunomediated pathways have been proposed. Genetic background appears to be important in determining susceptibility to the disease (2), but no clear association with alleles in the major histocompatibility complex has been identified. Molecular mimicry either by infections (3) or xenobiotics (4) has been proposed to be capable of breaking tolerance in genetically predisposed individuals, thus leading to onset of PBC. This article describes and discusses the available data regarding the immunomediated pathogenesis of PBC (with particular attention to auto-antibodies and autoreactive T-cells) and presents the recent evidence indicating a role for either xenobiotic chemicals or novel infectious agents in the induction of the disease.     

A comparative study on clinical characterizations between acute myelitis onset of neuromyelitis optica spectrum disease and idiopathic transverse myelitis

ABSTRACT

Background/Aims

Both of neuromyelitis optica spectrum disease (NMOSDs) and idiopathic transverse myelitis (ITM) could present as acute transverse myelitis. However, long-term immunological treatment and prognosis are different for high recurrence of NMOSDs. In this study, we summarized clinical differences between acute attack myelitis of NMOSDs and ITM, we further screened serum auto-antibodies to help understand the two distinct clinical entities.     

The auto-antigen repertoire in myasthenia gravis

Myasthenia Gravis (MG) is an antibody-mediated autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction (NMJ). MG is characterized by an impaired signal transmission between the motor neuron and the skeletal muscle cell, caused by auto-antibodies directed against NMJ proteins. The auto-antibodies target the nicotinic acetylcholine receptor (nAChR) in about 90% of MG patients. In approximately 5% of MG patients, the muscle specific kinase (MuSK) is the auto-antigen. In the remaining 5% of MG patients, however, antibodies against the nAChR or MuSK are not detectable (idiopathic MG, iMG). Although only the anti-nAChR and anti-MuSK auto-antibodies have been demonstrated to be pathogenic, several other antibodies recognizing self-antigens can also be found in MG patients. Various auto-antibodies associated with thymic abnormalities have been reported, as well as many non-MG-specific auto-antibodies. However, their contribution to the cause, pathology and severity of the disease is still poorly understood. Here, we comprehensively review the reported auto-antibodies in MG patients and discuss their role in the pathology of this autoimmune disease.     

Auto-immune-like cone dystrophy

Purpose: To describe rapid loss of cone vision in an adult due to putative auto-immune rejection. Methods: Clinical and electrophysiological examination, including full-field and multi-focal electroretinograms (ERGs), were used to assess retinal function. Serum was analyzed for antibodies to retinal antigens. Results: The patient lost cone vision in the course of several months while rod vision remained unaffected. Initially short wavelength (S) cone function appeared more resistant to the degeneration. Cancer associated retinal antibodies were present in the sera of the patient but no cancer has been found. Conclusion: Rapid loss of cone function can occur in an adult without a concomitant neoplasm although serum antibodies to retinal antigens suggest an autoimmune cause.     

Sex- and age-dependency of IgG auto-antibodies against IL-1α in healthy humans

Abstract. Naturally occurring anti-interleukin (IL)-1α IgG antibodies (Ab-IL-1α) were measured in sera of 466 healthy Danish blood donors. Ab-IL-1α bound IL-1α with exceptionally high affinity (Kd: 10^-11 M) and neutralized both cell-associated and extracellular IL-1α but not IL-1β or IL-1 receptor antagonist. More than 80% of the saturable binding of rIL-1α to serum was to Ab-IL-1α, suggesting that these antibodies are the quantitatively most important IL-1α-binding components in serum. Judged by second antibody precipitation assay, the prevalence of Ab-IL-1α varied between 30% and 75% and correlated positively with age ( P = 0·037). The binding capacity of serum also increased with age. Although men were more frequently positive than women ( P < 0·001), there were no sex- or age-dependent alterations in the average affinities of the antibodies. Free IL-1α-like molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab-IL-1α-positive sera contained low amounts of IL-1α-Ab-IL-1α immune complexes. IgG4 represented the main IgG isotype, whereas IgG3 Ab-IL-1α were undetectable. The relative amounts of IgG4 Ab-IL-1α increased while IgG2-and IgG1 Ab-IL-1α decreased in elderly individuals. The presence in normal individuals and the lack of affinity maturation with age suggest that Ab-IL-1α may be regulatory natural auto-antibodies perhaps coded by germline genes.     

EUROlineScan分析软件在免疫印迹法检测自身抗体中的应用探讨

目的比较目测判断法和EUROLineScan软件分析法在免疫印迹法检测自身抗体时的差异,为以显色条带灰度强度为基准的扫描软件分析法替代传统目测判断法提供实验依据。方法同时采用目测判断法和EUROlineScan软件分析法对免疫印迹法检测膜条显色带进行结果分析,并比较两种方法在结果判断上的差异;编写EUROlineScan软件与实验室信息系统(LIS)连接的接口,达到检测结果实时传入LIS的目的。结果在148条膜条的1184例自身抗体检测实验中,两种方法检测结果一致率为88.43%(1047/1184),κ=0.669,P=0.02;检测结果不一致主要集中分布于相邻两判断值间;目测判断法重复性为95.86%(1135/1184),而软件分析法的重复性为99.75%(1181/1184),两者比较有显著性差异(P=0.000)。结论EUROlineScan软件分析法较目测判断法在操作上更简便和快速,结果更客观、重复率更高,并可读取显色带具体的灰度值,同时具有能与LIS联机的特点,因此EUROlineScan软件分析法是免疫印迹法检测自身抗体结果判读更为有效可靠的方法。     

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...