Elevated serum levels of tumor necrosis factor-α in Guillain-Barré syndrome

Activated T lymphocytes and macrophages play a putative role in the pathogenesis of Guillian-Barré syndrome. Both cell types secrete tumor necrosis factor-α, a cytokine that has well-recognized toxi effects on myelin, Schwann cells, and endothelial cells. We determined serum and cerebrospinal fluid concentrations of tumor necrosis factor α in 26 patients with Guillain-Barré syndrome, 27 patients with other polyneuropathies, 30 patients with neurological diseases of the central nervous system, and 14 helthy control subjects. Markedly increased serum levels were detected in 14 patients(54%) with Guillian-Barré syndrome and to a significantly lesser extent, in patients with other polyneuropathies (26%) and in neurological control subjects(23%). Tumor necrosis factor-α was not detected in the cerebrospinal fluid of patients with Guillain-Barré syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain-Barré syndrome or other polyneuropathies. Increased serum concentrations in patients with Guillain-Barré syndrome correlated directly with disease severity and these concentrations returned to normal in parallel with clinical recovery. These findings emphasize the complexity of the immune response in patients with Guillain-Barré syndrome and suggest that tumor necrosis factor-αL may be important in the pathogenesis of peripheral demylination in this disorder.     

Increased serum interleukin-17 levels in patients with myasthenia gravis

It has been suggested that interleukin-17 (IL-17) plays a crucial role in the development of several autoimmune diseases. However, there are no data about the relationship between myasthenia gravis and IL-17. The aim of this study was to measure the concentration of IL-17 and determine whether levels depend on the severity of MG. Serum IL-17 concentrations were measured in 25 patients. IL-17 concentrations were higher in generalized MG compared with controls and correlated with anti-acetylcholinesterase receptor antibody titers.     

Expression of complement C3b/C4b receptors (CR1) on erythrocytes from patients with myasthenia gravis

The complement C3b/C4b receptor (CR1) expression on erythrocytes (E) (ECR1) from patients with myasthenia gravis (MG) and from blood donors was measured using haemadsorption and indirect hemagglutination techniques. The ECR1 expression in patients with MG appeared to be normal. This was also true for the subgroup of MG patients with additional autoimmune diseases. No correlation between ECR1 expression and severity of myasthenic symptoms was demonstrated.     

脑梗死后癫痫患者免疫球蛋白与补体的变化及意义

目的：探讨脑梗死后癫痫患者免疫球蛋白、补体的变化及意义。方法抽取我院2012-2013年36例脑梗死后癫痫患者、42例脑梗死史无癫痫患者及48例正常对照者静脉血各2mL,采用散射比浊法检测免疫球蛋白和补体含量,并进行分析。结果对照组、脑梗死无癫痫组、脑梗死后癫痫组血清IgA水平逐渐下降,差异有统计学意义（P＜0.05）。血清IgG、IgM、C3、C4浓度与对照组比较差异无统计学意义（P＞0.05）。多因素Logistic回归分析显示,梗死部位、血清IgA水平与脑梗死后癫痫发生有关。脑梗后癫痫患者血清IgA浓度ROC曲线下面积AUC＝0.821。结论IgA在脑梗死后癫痫发生机制中起作用。     

重症肌无力患者神经肌肉接头处的超微结构研究

目的探讨重症肌无力（ＭＧ）时神经肌肉接头（ＮＭＪ）突触后、前膜的变化及其意义。方法肋间内肌在辣根过氧化酶标记的α银环蛇毒素（ＨＲＰαＢｕＴｘ）标记后，用图形扫描及医学图像分析软件测量电镜照片中ＮＭＪ的各项指标，并与对照组比较分析。结果ＭＧ时突触后膜长度缩短，后、前膜长度比值变小，神经末端面积及其与突触后膜面积之比变小，突触后膜上的乙酰胆碱受体（ＡＣｈＲ）减少了３５．９％。结论ＭＧ时ＮＭＪ的变化主要存在于突触后膜。突触后、前膜长度之比对本病的诊断更有临床意义。     

重症肌无力病人智力、记忆力和情感障碍

目的研究重症肌无力（MG）病人智力、记忆力等认知功能及情感。方法采用龚氏修订的韦氏成人智力量表中国版、记忆量表中国版及抑郁自评量表，对31例MG病人及相匹配的22名正常对照以及25例其他疾病组进行检查研究。结果MG组大部分分测验值明显低于正常对照组及其他组，存在智力下降14例，其中智力缺陷6例；记忆力下降24例，其中记忆力明显损害19例，尤以短时记忆及瞬时记忆下降明显，全身型记忆力损害较眼肌型多。有主观抑郁症状者13例。结论MG病人中枢神经胆碱能系统可能受到损害，进而导致认知功能障碍。     

A novel ganglioside, 9-O-acetyl GD1b, is recognized by serum antibodies in Guillain-Barré syndrome

A hitherto undescribed ganglioside was detected in a crude ganglioside fraction of bovine brain using an IgM M-protein binding to Ga1β 1,3Ga1NAc residue. We purified and identified it as 9-O-acetyl GD1b based on results of alkali treatment that yielded GD1b and results of fast atom bombardment-mass and gas chromatography-mass spectrometries. 9-O-acetyl GD1b was also found to be present in human peripheral nerve tissue. The reactivities of the serum antibodies from patients with Guillain-Barré syndrome to 9-O-acetyl GD1b, GD1b, and GM1 were determined by ELISA and TLC immunostaining. Nineteen of 85 serum samples from Guillain-Barré syndrome patients had antibodies that bound to 9-O-acetyl GD1b: 14 of the positive samples also reacted with GM1 and GD1b, three reacted with GM1 but not with GD1b, one with GD1b but not with GM1, and one with neither GM1 nor GD1b. These results show that a subset of patients with Guillain-Barré syndrome had antibodies that react with 9-O-acetyl GD1b; therefore, this ganglioside can serve as a target antigen against the antibodies present in Guillain-Barré syndrome.     

Circulating tumor necrosis factor-α correlates with electrodiagnostic abnormalities in Guillain-Barré syndrome

Autoimmune damage to peripheral nerves, mediated by activated T lymphocytes and macrophages, underlies the pathogenesis of inflammatory demyelination in Guillain-Barré syndrome. Both T lymphocytes and macrophages secrete tumor necrosis factor-α, a cytokine that exerts toxic effects on myelin, Schwann cells, and endothelial cells. The reportedly high serum levels of this cytokine in patients with Guillain-Barré syndrome may reflect the degree of immune activation rather than a direct pathogenic effect. We compared serum levels of tumor necrosis factor-α, interleukin-1β, and soluble interleukin-2 receptor with well-established electrodiagnostic criteria for primary demyelination in 23 patients with Guillain-Barré syndrome, to assess the relationship between these cytokines and peripheral myelin damage. High serum levels of tumor necrosis factor-α were associated with prolonged distal motor latencies and slowed motor conduction velocities, prolonged or absent F-wave responses, and reduced amplitude of distal compound muscle action potentials. No significant correlation was observed between electrodiagnostic criteria for primary demyelination and serum levels of interleukin-1β or soluble interleukin-2 receptor. These findings suggest a putative role of tumor necrosis factor-α in the pathogenesis of peripheral nerve demyelination in Guillain-Barré syndrome.     

Circulating tumor necrosis factor (TNF)-α and soluble TNF-α receptors in patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an inflammatory disorder that may implicate proinflammatory cytokines such as TNF-α in its pathogenesis. We determined serum levels of TNF-α and the specific antagonists sTNF-Rs p55 and p75 in 24 patients with GBS at days 1, 15 and 30 of hospitalization. Patients were in the progression phase of the disease at day 1, and in the recovery phase at day 30. They were classified as able to walk (stage A), confined to bed (B), or under assisted ventilation (C). All patients underwent plasma exchange within day 1–12. At day 1, TNF-α levels were elevated in

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patients, and sTNF-Rs were elevated in

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. TNF-α levels had not decreased at day 15, and dropped at day 30 (p < 0.04), whereas sTNF-R p55 remained elevated at day 15 and day 30. The TNF-α/sTNF-Rs ratio, estimating active TNF-α unbound to sTNF-Rs, decreased from day 1 to day 30 (p < 0.05). A positive correlation was found between disease severity and sTNF-Rs serum levels (p < 0.01). In conclusion, elevated circulating sTNF-Rs assesses activation of the TNF-α system in almost all patients with GBS and correlates positively with disease severity. Drop of TNF-α contrasting with sustained elevation of sTNF-R p55 during recovery suggests that sTNF-R p55 may be important in the fading of the neural inflammatory effect of TNF-α in GBS.     

Soluble complement receptor type 1 in serum and cerebrospinal fluid of patients with Guillain-Barré syndrome and multiple sclerosis

Activation of complement is critically involved in inflammatory reactions in both Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). Soluble human complement receptor 1 (sCR1) blocks complement activation by both classical and alternative pathways. We studied serum and cerebrospinal fluid (CSF) concentrations of sCR1 in 23 patients with GBS, 27 patients with MS and 30 controls. No significant differences were found between patients and controls. Transient liver affection probably caused high serum sCR1 levels in two patients with GBS. The serum and CSF sCR1 levels were not correlated to the disease activity of GBS and MS, nor to the relapsing-remitting or chronic-progressive forms of MS. In GBS the CSF sCR1 levels correlated with the CSF total protein concentrations (r = 0.9, P < 0.01), suggesting that sCR leaks from serum into CSF via a damaged blood-nerve barrier. The serum sCRl levels in GBS were slightly higher than in MS (P < 0.05). Whether this reflects changes in the release or consumption of sCR in these patients is at present unknown.     

HLA and anti-GQ1b IgG antibody in Miller Fisher syndrome and Guillain-Barré syndrome

We investigated serological human leukocyte antigen (HLA) types in patients with histories of Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) with ophthalmoplegia, in whom serum anti-GQ1b IgG antibody was present during the acute phase. We examined class I antigens (A, B and C) in 32 patients and class II antigens (DR and DQ) in 30, but found no association. We conclude that particular serologically defined HLA types are not preferred for the immunoresponse of anti-GQ1b IgG antibody in MFS and GBS.     

Antibody of patients with Guillain-Barré syndrome mediates complement-dependent cytolysis of rat Schwann cells: Susceptibility to cytolysis reflects Schwann cell phenotype

We previously observed that demyelination of dissociated dorsal root ganglion cultures by acute phase serum of some Guillain Barré syndrome (GBS) patients was associated with cytolysis of rat Schwann cells (SC) not committed to myelination. In this study, to determine if SC cytolysis was antibody (Ab) and complement-dependent and if SC at various stages of differentiation were uniformly susceptible, sciatic nerve SC from 1–2-day-old (SC/2d) or 6-day-old (SC/6d) Sprague Dawley rats were sensitized with IgM from GBS patients or normal controls and incubated at 37°C for 60 min with 25% guinea pig serum complement. Cytolysis was detected by vital dye exclusion. IgM Ab of 11 GBS patients induced complement-mediated cytolysis of 10.7–64.1% SC/2d (38.3 ± 18.8; mean ± SD) which was significantly higher than cytolysis of SC/6d (8.5–32%) or that by normal controls (15.0 ± 15.2 SC/2d; 8.3 ± 3.3 SC/6d mean ± SD, n = 11). Culture of SC/6d increased their cytolysis by IgM plus complement to the levels similar to that of SC/2d. FACS analysis suggested that the greater sensitivity of SC/2d to cytolysis did not reflect greater antibody binding since 2.6-fold less GBS IgM was required to initiate SC/2d lysis compared to SC/6d. This suggested that the less differentiated SC were more susceptible to complement-mediated cytolysis.     

精神分裂症血清补体C3、C4、超敏C-反应蛋白及尿酸水平变化

目的探讨精神分裂症(schizophrenia,SZ)患者血清补体C3(complement component 3,C3)、C4(complement component 4,C4)、超敏C-反应蛋白(high sensitivity C reactive protein,hs-CRP)和尿酸(uric acid,UA)的水平变化及其临床意义。方法选择144例SZ患者为SZ组,并根据4周内有无服用抗精神病药物分为治疗组(77例)和停药组(67例),另选择同期来湘雅二医院的健康体检者147例为健康对照组。采用免疫散射比浊法、胶乳增强免疫比浊法、尿酸氧化酶法分别测定各组血清补体C3、C4、hs-CRP和UA浓度,并比较分析。结果 SZ组患者血清补体C3、C4水平低于对照组[(0.99±0.17)g/L vs.(1.03±0.17)g/L、(0.21±0.05)g/L vs.(0.23±0.05)g/L],UA水平高于对照组[(351.61±95.90)μmol/L vs.(300.28±39.57)μmol/L],差异有统计学意义(分别P0.05,P0.05,P0.001)。治疗组患者血清补体C3、C4、hs-CRP和UA水平较停药组均升高[(1.04±0.19)g/L vs.(0.95±0.15)g/L、(0.22±0.06)g/L vs.(0.20±0.05)g/L、1.08(0.33,5.04)mg/L vs.0.47(0.28,1.29)mg/L、(374.54±108.33)μmol/L vs.(331.61±79.03)μmol/L],差异均有统计学意义(P0.01)。治疗组患者血清hs-CRP和UA浓度较对照组均升高[1.08(0.33,5.04)mg/L vs.0.61(0.33,1.26)mg/L、(374.54±108.33)μmol/L vs.(300.28±39.57)μmol/L],差异有统计学意义(P0.001)。结论 SZ患者血清C3、C4、hs-CRP和UA的水平变化对SZ临床诊断和抗精神病药物疗效评估有一定指导意义。     

Association between glycoconjugate antibodies and Campylobacter infection in patients with Guillain-Barré syndrome

In a retrospective study we have analysed sera from a well-characterised Guillain-Barré syndrome (GBS) patient group for antibodies that react with gangliosides. Of 95 GBS patients and 85 control patients analysed, we found that 14 (15%) of GBS patients but only one control patient had antibodies that react with the gangliosides G_M1 and/or G_D1b but not G_M2, G_D1a and G_T1b using a sensitive enzyme-linked immunosorbent assay (ELISA). This pattern of reactivity suggests binding to the carbohydrate structure Gal(β1–3)GalNAc which is shared between some glycolipids and glycoproteins. Similar antibodies have been found previously in a subpopulation of patients with lower motor neuron disease. In the present study, the predominant immunoglobulin class of these anti-glycoconjugate antibodies was IgG rather than IgM. A correlation was found between the presence of these antibodies and prognosus in terms of disability at 3 and 12 months after presentation. Patients with anti-glycoconjugate antibodies also had a higher incidence of previous Campylobacter infections than the rest of the patient group, although the significance of this remains to be determined.     

T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barré syndrome

T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4⁺) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease to define circulating T cell populations. The proportion of T-helper cells (CD4⁺) was decreased (mean value 41±15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells (CD8⁺) was increased (35±18%, P = 0.0006) as compared to the control group of healthy blood donors (47±8% and 26±7% respectively). The CD4⁺ population is divided into the helper/inducer (CD4⁺ CD29⁺) and suppressor/inducer (CD4⁺ CD45RA⁺) subsets. which normally are equally distributed (mean values in our control group were 45±15% and 44±15%, respectively). In patients with GBS, the helper/inducer (CD4⁺ CD29⁺) subset was increased (54±10%, P = 0.05) and the suppressor/inducer (CD4⁺ CD45RA⁺) subset was decreased (31±9, P = 0.005) compared to the controls. The proportion of activated HLA-DR-expressing T cells was increased (7±8%, P = 0.005) as compared to control (3±3%). The total proportions of T cells (CD2⁺), B cells (CD19⁺) and natural killer (NK) cells (CD56⁺) were similar in pateints and controls. The CD4⁺ and CD8⁺ populations, as well as the activated HLA-DR⁺ T cells, normalized during the disease course. The derivations within the CD4⁺ population also tended to normalize, but even at follow up after 6–33 (mean 23) months, some abnormalities remained. In conclusion, we confirm previous reports of T cell activation in peripheral blood from patients with GBS. A new finding is the derivation of T helper subpopulations with an increased helper/inducer (CD4⁺ CD29⁺) subset and a decreased suppressor/inducer (CD4⁺ CD45RA⁺) subset, which indicates a possible autoimmune character of GBS.     

An electrophysiological study of the effects of myasthenia gravis sera and complement on rat isolated muscle fibres

The effect of human myasthenia gravis (MG) sera and complement on isolated adult rat muscle fibres was investigated. Heat-inactivated MG sera reduced the frequency of single acetylcholine receptor (AChR)-channel activity. One of the MG sera tested had a stronger effect on the extrajunctional type of AChRs than on the junctional type. The simultaneous addition of normal human serum (NHS), as source of complement, and MG serum to freshly dissociated muscle fibres caused contraction restricted to the endplate area and progressive depolarization of the muscle membrane, followed by contracture. An MG antibody-dependent complement-mediated damaged of the muscle fibres is suggested.     

Diagnostic significance of IgG, C3, and C9 at the limb muscle motor end-plate in minimal myasthenia gravis

We detected deposits of IgG, C3, and C9 (immune complexes) at the limb muscle motor end-plates (biceps brachii muscle) in 16 of 19 patients who exhibited only ocular signs and symptoms of myasthenia gravis that were improved by intravenous injections of edrophonium chloride. Circulating anti-acetylcholine receptor (anti-AChR) antibodies were negative in 6 of the 16 patients, but the motor end-plate fine structure in the postsynaptic regions was abnormal in all 16. Single-fiber EMG revealed no abnormalities in 8 of 13 patients studied. Our results indicate that the detection of immune complexes at the limb muscle end-plate provides a highly sensitive and confirmative method for diagnosing patients with minimal or atypical myasthenia gravis who have no detectable anti-AChR antibodies in their serum.     

Health-related quality of life in patients with myasthenia gravis and the relationship between patient-oriented assessment and conventional measurements

We assessed the health-related quality of life (HRQoL) of patients with myasthenia gravis (MG) and correlated it with the physician's measurements of MG. Patients with MG were evaluated by means of (1) self-administered questionnaires, (2) clinical examination, (3) Osserman classification, (4) anti-AChR antibody, and (5) neurophysiology. Relationships between patient-oriented assessment and conventional clinical-neurophysiological and serological findings were evaluated. A total of 46 patients, inpatients and outpatients (mean age 50.7 years, range 11-77 years, 17 males, 29 females) with MG diagnosis were studied. The Osserman scale and clinical examination findings were significantly related to the physical aspects of HRQoL. Mental aspects of the quality of life were not progressively involved as muscle deficit progressed, but even in a mild clinical picture, the mental aspects were deteriorated. Patient-oriented measures proved that the patient's quality of life was impaired especially with regard to physical aspects. Our data demonstrated that clinical measurements are related to the HRQoL. The results may be useful in developing a disease-specific patient-oriented tool.     

Fcγ receptors and HLA-DR antigens on thymus cells in myasthenia gravis

Receptors for the Fc part of IgG (FcγR) and HLA-DR antigens were detected in thymus tissue from patients with myasthenia gravis (MG) using monoclonal antibodies (B1D6 and OKIa1) in indirect immunofluorescence. The amount of FcγR and HLA-DR antigens was increased on epithelial reticular cells and on interdigitating reticular cells in hyperplastic thymus as compared to normal thymus. In thymomas from MG patients the neoplastic epithelial cells expressed FcγR, whereas only a few cells had HLA-DR antigens. Neither thymocytes nor B lymphocytes in the hyperplastic thymuses and in the thymomas were stained by B1D6.     

Role of therapeutic plasmapheresis in the acute Guillain-Barré syndrome

Plasmapheresis modifies the course of the acute Guillain-Barré syndrome (GBS) in terms of time-related parameters such as time on a respirator or time to achieve a specific area of improvement at specific times after onset of the illness such as at 1 month and at 6 months.

Certain factors are associated with poorer outcomes in acute GBS. These include amplitude of compound muscle axon potentials on stimulating distally, time of onset of disease of 7 days or less, need for ventilatory support, and older age. Plasmapheresis, the only variable that the physician can influence, has a beneficial effect over and above all these factors.