GAD65 antibodies

  • 文章类型: Journal Article
    僵硬的人综合征谱系障碍(SPSD)对胃肠道(GIT)的影响尚不清楚。本病例系列旨在描述SPSD患者胃肠道功能障碍的患病率和类型。
    回顾性图表回顾包括诊断为SPSD的个体,其医疗记录中有胃肠道症状的描述。SPSD表型,进行的运动性测试类型,和运动障碍模式(上部,较低,或弥漫性)进行评估。利用描述性统计和单变量卡方分析。
    在240名SPSD患者中,32%报告了胃肠道症状,大多数是女性(83.1%),白人(74%)胃肠道症状发作时的中位年龄为50±13岁。报告的最常见症状是吞咽困难(45%),便秘(40%),恶心/呕吐(23%)。大多数个体有经典SPS(47%),其次是SPS-plus(29%)和82.9%的血清抗GAD65抗体阳性。在36名接受至少一次胃肠动力测试的患者中,26有上层的证据,较低,或弥漫性胃肠动力障碍(44.4%,17%,4%,分别)。未接受测试的组的DM患者比例较高。
    在SPSD患者中,胃肠道症状和转运异常的患病率很高。未来的前景,有必要进行纵向研究,以进一步评估SPSD背景下的胃肠道症状,并确定有胃肠道症状的个体与无胃肠道症状的个体在预后或治疗反应方面是否存在差异.同时,SPSD患者的运动试验阈值应该较低.
    UNASSIGNED: The effect of stiff person syndrome spectrum disorders (SPSD) on the gastrointestinal tract (GIT) is unknown. This case series aims to characterize the prevalence and types of GI dysfunction in individuals with SPSD.
    UNASSIGNED: A retrospective chart review included individuals diagnosed with SPSD with descriptors of GI symptoms in their medical records. SPSD phenotypes, type of motility test performed, and dysmotility pattern (upper, lower, or diffuse) were assessed. Descriptive statistics and univariate chi-square analyses were utilized.
    UNASSIGNED: Of 240 individuals with SPSD, 32% reported GI symptoms, most were female (83.1%), and white (74%), with a median age at time of GI symptom onset of 50 ± 13 years. Most common symptoms reported were dysphagia (45%), constipation (40%), and nausea/vomiting (23%). Most individuals had classic SPS (47%) followed by SPS-plus (29%) and 82.9% were positive for serum antiGAD65 antibodies. Of 36 patients that underwent at least one GI motility test, 26 had evidence of upper, lower, or diffuse GI dysmotility (44.4%, 17%, and 4%, respectively). The group who did not undergo testing had a higher proportion of patients with DM.
    UNASSIGNED: There is a high prevalence of GI symptoms and transit abnormalities in patients with SPSD. Future prospective, longitudinal studies are warranted to further assess GI symptoms in the context of SPSD and to determine if individuals with GI symptoms differ in prognosis or treatment response from those without GI symptoms. In the meantime, there should be a low threshold for motility testing in patients with SPSD.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    未经证实:边缘叶脑炎是颞叶内侧癫痫(mTLE)和相关认知缺陷的日益公认的原因,可能导致海马硬化(HS)。出于几个原因,这些患者通常不接受癫痫手术。因此,在明确诊断的边缘叶脑炎的手术标本中,组织病理学检查很少。这项研究的目的是对手术组织改变进行详细的组织病理学分析,包括神经退行性标记物,接受癫痫手术的边缘叶脑炎患者。
    UNASSIGNED:我们调查了6例与边缘叶脑炎相关的mTLE患者的手术标本(其中4例患者为GAD65,1例患者为Ma1/2抗体),并将结果与对照组进行了比较,对照组为6例患者,根据手术时的年龄相匹配,无边缘叶脑炎且无早期煽动事件。
    UNASSIGNED:边缘叶脑炎组的组织病理学分析显示4例患者出现HS,而其中三个还显示出淋巴细胞活跃的炎症反应。在患有GAD65脑炎的患者中,有一名患有晚发性mTLE和病程较长的患者,发现神经退行性蛋白标志物(β-淀粉样蛋白和高磷酸化tau)与炎症反应和HS共存。对照组的研究未发现任何炎症反应或神经变性标志物。
    未经证实:我们的研究结果表明,颞叶内侧持续的免疫反应之间可能存在联系,HS,并进一步发展神经退行性疾病。目前,然而,这些实体之间的因果关系尚无法确定。此外,我们的结果表明,在晚期(>18岁)的mTLE中,应始终考虑免疫学病因,在疾病持续时间长和存在HS的情况下也是如此。
    UNASSIGNED: Limbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery.
    UNASSIGNED: We investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events.
    UNASSIGNED: Histopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (β-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker.
    UNASSIGNED: Our findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    在过去的20年中,我们对自身免疫性和副肿瘤性小脑共济失调的认识取得了重大进展。几种神经抗体的发现代表了这一领域不可否认的贡献,特别是那些作为副肿瘤神经综合征的良好生物标志物和那些显示直接致病作用的生物标志物。然而,许多患者仍然缺乏可检测或已知的抗体,而且许多抗体仅在少数患者中被报道,这使得很难详细定义它们的临床价值。然而,在具有主要神经抗体的患者的临床表征方面也取得了显着进展,which,尽管通常表现为亚急性小脑大范围综合征,也可能显示超急性或慢性发作,使鉴别诊断复杂化。然而,前驱和瞬时特征可能是早期识别的有用线索,脑外侧受累也可能高度指示相关抗体。此外,我们对小脑共济失调发病机制的理解的重要进展包括抗体效应的描述,尤其是那些靶向细胞表面抗原的,并首次尝试分离抗原特异性T细胞。此外,遗传倾向似乎相关,尽管根据癌症协会的不同参与,在非副肿瘤病例中观察到特殊的HLA,而副肿瘤病例中肿瘤细胞的遗传异常。最后,用作癌症免疫疗法的免疫检查点抑制剂可能很少诱导小脑共济失调,但是,即使这种不良作用也可能反过来有助于阐明其病理生理学。在这里,我们回顾了过去20年关于自身免疫性和副肿瘤性小脑共济失调的主要新发现。
    Major advances in our knowledge concerning autoimmune and paraneoplastic cerebellar ataxias have occurred in the last 20 years. The discovery of several neural antibodies represents an undeniable contribution to this field, especially those serving as good biomarkers of paraneoplastic neurological syndromes and those showing direct pathogenic effects. Yet, many patients still lack detectable or known antibodies, and also many antibodies have only been reported in few patients, which makes it difficult to define in detail their clinical value. Nevertheless, a notable progress has additionally been made in the clinical characterization of patients with the main neural antibodies, which, although typically present with a subacute pancerebellar syndrome, may also show either hyperacute or chronic onsets that complicate the differential diagnoses. However, prodromal and transient features could be useful clues for an early recognition, and extracerebellar involvement may also be highly indicative of the associated antibody. Moreover, important advances in our understanding of the pathogenesis of cerebellar ataxias include the description of antibody effects, especially those targeting cell-surface antigens, and first attempts to isolate antigen-specific T-cells. Furthermore, genetic predisposition seems relevant, although differently involved according to cancer association, with particular HLA observed in non-paraneoplastic cases and genetic abnormalities in the tumor cells in paraneoplastic ones. Finally, immune checkpoint inhibitors used as cancer immunotherapy may rarely induce cerebellar ataxias, but even this undesirable effect may in turn serve to shed some light on their physiopathology. Herein, we review the principal novelties of the last 20 years regarding autoimmune and paraneoplastic cerebellar ataxias.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    UNASSIGNED: Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA).
    UNASSIGNED: To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity.
    UNASSIGNED: 113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide.
    UNASSIGNED: Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide.
    UNASSIGNED: GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity.
    UNASSIGNED: NCT01696747.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    暂无摘要。
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

  • 文章类型: Journal Article
    BACKGROUND: Glutamate decarboxylase is an intracellular enzyme converting glutamate into GABA. Antibodies (abs) to its isoform GAD65 were described in limbic encephalitis and other neurological conditions. The significance of GAD65 abs for epilepsy is unclear, but alterations of inhibitory GABAergic neurotransmission may be involved. Here, we investigated the effects of the serum of a female patient suffering from GAD65 ab-associated LE on GABAA currents in cultured hippocampal networks.
    METHODS: Spontaneous or evoked post-synaptic GABAA currents were measured in cultured hippocampal neurons prepared from embryonic mice after 11-21 days in vitro using the patch-clamp technique in the whole-cell mode after incubation with serum of a healthy control or the LE-patient at a final concentration of 1% for 5-8 h.
    RESULTS: Properties of miniature inhibitory post-synaptic currents were not different in cultures treated with control and LE-serum. Likewise, paired-pulse ratio of evoked GABAA currents as a measure of release probability was not different in both conditions. Evoked GABAA currents were significantly depressed during 10 Hz stimulation without significant differences between control and LE-serum treated cultures.
    CONCLUSIONS: In our experimental paradigms, serum of a patient with confirmed GAD65 ab-associated LE had no apparent effect on GABAergic neurotransmission in murine-cultured hippocampal networks. These results challenge the view that the presence of GAD65 abs invariably compromise inhibitory network function.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

  • 文章类型: Journal Article
    BACKGROUND: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM.
    METHODS: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into OSAS[-] and OSAS[+] were assessed for cardiometabolic risk factors, glucose homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD); and GAD65 antibodies.
    RESULTS: There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate.
    CONCLUSIONS: We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Sci-hub)

公众号