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Monitoring of Soluble Forms of BAFF System (BAFF, APRIL, sR-BAFF, sTACI and sBCMA) in Kidney Transplantation 肾移植中BAFF系统可溶性形态(BAFF, APRIL, sR-BAFF, sTACI和sBCMA)的监测
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-09-22 DOI: 10.1007/s00005-022-00659-4
Rafael Alfaro, Santiago Llorente, Pedro Martinez, Víctor Jimenez-Coll, Helios Martínez-Banaclocha, José Antonio Galián, Carmen Botella, María Rosa Moya-Quiles, Jesús de la Peña-Moral, Alfredo Minguela, Isabel Legaz, Manuel Muro

BAFF system plays an essential role in B cells homeostasis and tolerance, although it has widely not been tested in transplantation with doubtful results. The main purpose was to study the BAFF soluble forms and their correlation with acute rejection (AR) and donor-specific antibodies production. Serum levels of BAFF, APRIL, and soluble forms of their receptors were analyzed in renal recipients with and without acute rejection (AR/NAR) appearance. All molecules were evaluated at pre- and post-transplantation. sTACI showed a significant correlation with BAFF and sR-BAFF levels, and sBCMA also showed a positive correlation with sAPRIL levels. A significant increase in sAPRIL levels in patients suffering AR was also found, and ROC curves analysis showed an AUC = 0.724, a concentration of 6.05 ng/ml (sensitivity: 66.7%; specificity: 73.3%), the best cutoff point for predicting AR. In the post-transplant dynamics of sAPRIL levels in the longitudinal cohort, we observed a significant decrease at 3 and 6 month post-transplantation compared to pretransplantation status. We also observed that recipients with high pre-transplant levels of sAPRIL generated antibodies earlier than those with lower sAPRIL levels, although their long-term post-transplantation was not different. Our results show that elevated serum levels of APRIL may be helpful as a biomarker for the diagnosis of AR, although the longitudinal study shows that it is not helpful as a prognostic biomarker.

BAFF系统在B细胞稳态和耐受性中起着重要作用,尽管在移植中广泛未被测试,结果可疑。主要目的是研究BAFF可溶性形式及其与急性排斥反应(AR)和供体特异性抗体产生的关系。在有和没有急性排斥反应(AR/NAR)出现的肾受者中,分析血清BAFF、APRIL及其受体的可溶性形式。在移植前后对所有分子进行评价。sTACI与BAFF、sR-BAFF呈显著相关,sBCMA与sAPRIL呈显著正相关。AR患者的sAPRIL水平也显著升高,ROC曲线分析显示AUC = 0.724,浓度为6.05 ng/ml(敏感性:66.7%;特异性:73.3%),是预测AR的最佳截止点。在纵向队列的移植后动态中,我们观察到移植后3个月和6个月的sAPRIL水平与移植前状态相比显著下降。我们还观察到,移植前sAPRIL水平高的受者比sAPRIL水平低的受者更早产生抗体,尽管他们在移植后的长期没有差异。我们的研究结果表明,血清APRIL水平升高可能有助于作为AR诊断的生物标志物,尽管纵向研究表明它不能作为预后的生物标志物。
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引用次数: 1
Long-Term Biodistribution and Safety of Human Dystrophin Expressing Chimeric Cell Therapy After Systemic-Intraosseous Administration to Duchenne Muscular Dystrophy Model 人肌营养不良蛋白表达嵌合细胞治疗杜氏肌营养不良模型后的长期生物分布和安全性
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-17 DOI: 10.1007/s00005-022-00656-7
Maria Siemionow, Sonia Brodowska, Paulina Langa, Kristina Zalants, Katarzyna Kozlowska, Wictoria Grau-Kazmierczak, Ahlke Heydemann

Duchenne muscular dystrophy (DMD) is a lethal disease caused by X-linked mutations in the dystrophin gene. Dystrophin deficiency results in progressive degeneration of cardiac, respiratory and skeletal muscles leading to premature death due to cardiopulmonary complications. Currently, no cure exists for DMD. Based on our previous reports confirming a protective effect of human dystrophin expressing chimeric (DEC) cell therapy on cardiac, respiratory, and skeletal muscle function after intraosseous administration, now we assessed long-term safety and biodistribution of human DEC therapy for potential clinical applications in DMD patients. Safety of different DEC doses (1 × 106 and 5 × 106) was assessed at 180 days after systemic-intraosseous administration to mdx/scid mice, a model of DMD. Assessments included: single cell gel electrophoresis assay (COMET assay) to confirm lack of genetic toxicology, magnetic resonance imaging (MRI) for tumorigenicity, and body, muscle and organ weights. Human DEC biodistribution to the target (heart, diaphragm, gastrocnemius muscle) and non-target (blood, bone marrow, lung, liver, spleen) organs was detected by flow cytometry assessment of HLA-ABC markers. Human origin of dystrophin was verified by co-localization of dystrophin and human spectrin by immunofluorescence. No complications were observed after intraosseous transplant of human DEC. COMET assay of donors and fused DEC cells confirmed lack of DNA damage. Biodistribution analysis of HLA-ABC expression revealed dose-dependent presence of human DEC cells in target organs, whereas negligible presence was detected in non-target organs. Human origin of dystrophin in the heart, diaphragm and gastrocnemius muscle was confirmed by co-localization of dystrophin expression with human spectrin. MRI revealed no evidence of tumor formation. Body mass and muscle and organ weights were stable and comparable to vehicle controls, further confirming DEC safety at 180 days post- transplant. This preclinical study confirmed long-term local and systemic safety of human DEC therapy at 180 days after intraosseous administration. Thus, DEC can be considered as a novel myoblast based advanced therapy medicinal product for DMD patients.

杜氏肌营养不良症(DMD)是一种由肌营养不良蛋白基因x连锁突变引起的致死性疾病。肌营养不良蛋白缺乏导致心脏、呼吸和骨骼肌进行性变性,导致心肺并发症导致过早死亡。目前,还没有治愈DMD的方法。基于我们之前的报告证实了人表达抗肌营养不良蛋白的嵌合细胞(DEC)治疗对骨内给药后心脏、呼吸和骨骼肌功能的保护作用,现在我们评估了人DEC治疗在DMD患者中的潜在临床应用的长期安全性和生物分布。在DMD模型mdx/scid小鼠全身骨内给药180天后,评估不同剂量(1 × 106和5 × 106) DEC的安全性。评估包括:单细胞凝胶电泳测定(COMET测定)以确认缺乏遗传毒理学,核磁共振成像(MRI)检测致瘤性,以及身体、肌肉和器官重量。用流式细胞术评估HLA-ABC标记物,检测人DEC在靶器官(心脏、膈肌、腓肠肌)和非靶器官(血液、骨髓、肺、肝、脾)的生物分布。通过免疫荧光法对肌营养不良蛋白和人谱蛋白的共定位,证实了肌营养不良蛋白的人源性。人DEC骨内移植后无并发症,供体和融合DEC细胞的彗星测定证实无DNA损伤。HLA-ABC表达的生物分布分析显示,人DEC细胞在靶器官中存在剂量依赖性,而在非靶器官中检测到可忽略不计的存在。人类来源于心脏、膈肌和腓肠肌的肌营养不良蛋白与人谱蛋白的表达共定位证实。MRI未见肿瘤形成。体质量、肌肉和器官重量稳定,与对照组相当,进一步证实了移植后180天DEC的安全性。这项临床前研究证实了骨内给药后180天人DEC治疗的长期局部和全身安全性。因此,DEC可被认为是一种新型的基于成肌细胞的DMD患者高级治疗药物。
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引用次数: 4
Immunotherapy in Ovarian Cancer 卵巢癌的免疫治疗
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-09 DOI: 10.1007/s00005-022-00655-8
Natalia Siminiak, Rafał Czepczyński, Mikołaj Piotr Zaborowski, Dariusz Iżycki

Despite advances in surgery and chemotherapy, ovarian cancer remains one of the most lethal malignancies. Hence, the implementation of novel treatment approaches is required to improve the outcomes of the disease. Immunotherapy has been proven to be effective in many tumors and has already been incorporated into clinical practice. In this review, we describe key strategies in immunotherapy of ovarian cancer and summarize data from clinical studies assessing immunological prospects which could improve ovarian cancer treatment approaches in the future. The most notable current strategies include checkpoint blockade agents, the use of vaccines, adoptive cell transfer, as well as various combinations of these methods. While several of these options are promising, large controlled randomized studies are still needed to implement new immunotherapeutic options into clinical practice.

尽管在手术和化疗方面取得了进展,卵巢癌仍然是最致命的恶性肿瘤之一。因此,需要实施新的治疗方法来改善疾病的结果。免疫疗法已被证明对许多肿瘤有效,并已被纳入临床实践。在这篇综述中,我们描述了卵巢癌免疫治疗的关键策略,并总结了评估免疫学前景的临床研究数据,这些数据可以改善未来卵巢癌的治疗方法。目前最值得注意的策略包括检查点阻断剂、疫苗的使用、过继细胞转移以及这些方法的各种组合。虽然这些选择中有几个是有希望的,但仍然需要大规模的对照随机研究来将新的免疫治疗选择应用于临床实践。
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引用次数: 3
Elevated Levels of Soluble CD147 are Associated with Hyperinflammation and Disease Severity in COVID-19: A Proof-of-Concept Clinical Study 可溶性CD147水平升高与COVID-19的高炎症和疾病严重程度相关:一项概念验证临床研究
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-08-03 DOI: 10.1007/s00005-022-00657-6
Rashidi Springall, Julieta González-Flores, Carlos García-Ávila, Yaneli Juárez-Vicuña, Adrián Hernández-Diazcouder, Ricardo Márquez-Velasco, Sergio Cásares-Alvarado, Fausto Sánchez-Muñoz, Edna Basilio-Gálvez, Mauricio Castillo-Salazar, Martha A. Ballinas-Verdugo, Malinalli Brianza-Padilla, José L. Sánchez-Gloria, Claudia Tavera-Alonso, Julio Sandoval, Héctor González-Pacheco, Luis M. Amezcua-Guerra

To evaluate soluble CD147 levels in COVID-19 and identify whether these are associated with hyperinflammation and disease severity. One-hundred and nine COVID-19 patients and 72 healthy blood donors were studied. Levels of CD147, matrix metalloproteases (MMP) and inflammatory markers were measured on hospital arrival, while the need for mechanical ventilation and the occurrence of death during hospitalization were recorded. CD147 levels were higher in COVID-19 (1.6, 1.0–2.3 vs 1.3, 1.0–1.6 ng/ml; P = 0.003) than controls. MMP-2 (9.2, 4.5–12.9 vs 4.2, 3.7–4.6 ng/ml; P < 0.001), MMP-3 (1.1, 0.9–1.3 vs 0.9, 0.7–1.0 ng/ml; P < 0.001) and MMP-9 (0.9, 0.5–1.2 vs 0.4, 0.2–0.6 ng/ml; P < 0.001) were also higher in COVID-19, while MMP-1 (0.6, 0–1.4 vs 0.6, 0.3–0.7 ng/ml; P = 0.711) was not different. Significant correlations were found between CD147 and MMP-2 (ρ = 0.34), MMP-3 (ρ = 0.21), interleukin 6 (ρ = 0.21), and the neutrophil/lymphocyte ratio (ρ = 0.26). Furthermore, CD147 levels were higher in patients who required mechanical ventilation (1.8, 1.4–2.4 vs 1.2, 0.8–1.9 ng/ml; P < 0.001) and in those who ultimately died (1.9, 1.4–2.7 vs 1.4, 0.9–1.9 ng/ml; P = 0.009). CD147 is elevated in COVID-19 and appears to contribute to hyperinflammation and disease severity.

评估COVID-19中可溶性CD147水平,并确定这些水平是否与过度炎症和疾病严重程度相关。对109名新冠肺炎患者和72名健康献血者进行了研究。在到达医院时测量CD147、基质金属蛋白酶(MMP)和炎症标志物的水平,同时记录住院期间机械通气的需要和死亡的发生。CD147水平在COVID-19中较高(1.6,1.0-2.3 vs 1.3, 1.0-1.6 ng/ml;P = 0.003)。MMP-2 (9.2, 4.5-12.9 vs 4.2, 3.7-4.6 ng/ml;P & lt; 0.001), MMP-3(1.1、0.9 - -1.3 vs 0.9 0.7 -1.0 ng / ml;P & lt; 0.001)和MMP-9(0.9、0.5 - -1.2 vs 0.4 0.2 -0.6 ng / ml;P < 0.001),而MMP-1 (0.6, 0-1.4 vs 0.6, 0.3-0.7 ng/ml;P = 0.711)差异无统计学意义。CD147与MMP-2 (ρ = 0.34)、MMP-3 (ρ = 0.21)、白细胞介素6 (ρ = 0.21)和中性粒细胞/淋巴细胞比值(ρ = 0.26)有显著相关性。此外,需要机械通气的患者CD147水平更高(1.8,1.4-2.4 vs 1.2, 0.8-1.9 ng/ml;P < 0.001)和最终死亡的患者(1.9,1.4 - 2.7 vs 1.4, 0.9-1.9 ng/ml;p = 0.009)。CD147在COVID-19中升高,似乎有助于过度炎症和疾病严重程度。
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引用次数: 6
The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice 吸入空气颗粒物SRM 1648a对DBA/J小鼠轻度胶原性关节炎发展的影响
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-07-28 DOI: 10.1007/s00005-022-00654-9
Bernadeta Nowak, Grzegorz Majka, Małgorzata Śróttek, Anna Skałkowska, Janusz Marcinkiewicz

Air pollution is considered to be one of a risk factor for rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is commonly used as a mouse model of human RA. However, the impact of specific particulate matter (PM) components on the incidence and severity of RA has still not been established. The aim of this study was to develop an experimental model of CIA suitable to test arthritogenicity of inhaled PM. A mild form of CIA was induced in DBA1/J mice inhaled with various components of SRM 1648a PM. The incidence and severity of arthritis was assessed, and the selected serum markers of autoimmunity and inflammation were determined. Clinical arthritis was observed from the booster CII immunisation onward. Anti-cyclic citrullinated peptide antibodies, a diagnostic marker of RA, were detected in serum of these mice. All inhaled pollutants, crude PM, PM with reduced organic content, ferric, and silica nanoparticles markedly increased CIA incidence and severity. The fastest progression of CIA development was caused by crude PM and was linked to enhanced serum levels of anti-CII IgG, the prominent arthritogenic autoantibodies. On the other hand, inhaled nanoparticles enhanced serum levels of TNFα, a major proinflammatory arthritogenic cytokine. We recommend this experimental model of mild CIA to test the mechanisms of arthritis exacerbation by inhaled air pollutants. Further studies are necessary to determine whether PM-aggravated arthritis is caused by inflammatory mediators translocated from inflamed lung into systemic circulation or whether PM translocated into the bloodstream directly exacerbate joint inflammation.

空气污染被认为是类风湿性关节炎(RA)的危险因素之一。胶原诱导关节炎(CIA)是常用的人类类风湿性关节炎小鼠模型。然而,特定颗粒物(PM)成分对RA发病率和严重程度的影响尚不明确。本研究旨在建立一种适合于检测吸入PM致关节炎性的CIA实验模型。用SRM 1648a PM的不同组分吸入DBA1/J小鼠,诱导轻度CIA。评估关节炎的发病率和严重程度,并选择自身免疫和炎症的血清标志物进行测定。临床关节炎观察从加强CII免疫后。在小鼠血清中检测到RA诊断标志物抗环瓜氨酸肽抗体。所有吸入污染物、粗颗粒物、有机含量降低的颗粒物、铁和二氧化硅纳米颗粒都显著增加了CIA的发病率和严重程度。CIA发展的最快进展是由粗PM引起的,并与血清抗cii IgG(主要的关节炎自身抗体)水平升高有关。另一方面,吸入纳米颗粒可提高血清TNFα水平,TNFα是一种主要的促炎关节炎细胞因子。我们推荐这个轻度CIA的实验模型来测试吸入空气污染物导致关节炎恶化的机制。PM加重的关节炎是由炎症介质从发炎的肺部转移到体循环引起的,还是PM转移到血液中直接加剧了关节炎症,还需要进一步的研究来确定。
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引用次数: 4
Sex Differences in Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients 阿尔茨海默病患者外周血白细胞先天免疫反应的性别差异
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-06-16 DOI: 10.1007/s00005-022-00653-w
Marta Sochocka, Michał Ochnik, Maciej Sobczyński, Beata Orzechowska, Jerzy Leszek

Neurodegenerative disorders, including Alzheimer’s disease (AD), are associated with a disruption of normal immune function that could potentially impact the brain. In AD sex and gender have been noted as relevant to disease prevalence or clinical manifestation. It is suggested that disease progression could vary as a result of the different inflammation state among males and females. The objective was to investigate sex-dependent difference in innate immunity of AD patients and healthy, age-matched controls. The level of innate immunity was measured with test based on peripheral blood leukocytes (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo. Cytokine: TNF-α, IFN-γ, IL-1β, IL-10 production by uninfected and VSV-infected PBLs ex vivo with enzyme-linked immunosorbent assay were examined. In contrast to controls, women with AD exhibit lower average level of innate immunity than AD men. The mean level of TNF-α, IL-10 and IL-1β was higher in AD men than in AD women whereas such changes were not observed among controls. The level of IFN-γ was higher in AD than in controls. PBLs from AD did not increase IFN-γ production after viral infection in contrast to controls. Leukocytes from women with AD exhibited a weaker response to viral infection and much less cytokine production compared to men with AD. It is important to consider sex as a biological variable in AD as it shows promises to advance our understanding of mechanisms of AD pathology and may be the basis for future treatment of AD.

包括阿尔茨海默病(AD)在内的神经退行性疾病与正常免疫功能的破坏有关,这可能会影响大脑。在AD中,性别和性别被认为与疾病流行率或临床表现有关。研究表明,男性和女性的炎症状态不同,疾病进展可能会有所不同。目的是研究AD患者和健康、年龄匹配的对照组先天免疫的性别依赖性差异。先天免疫水平是通过基于外周血白细胞(PBL)对病毒感染(水泡性口腔炎病毒,VSV)的体外抵抗力的测试来测量的。用酶联免疫吸附法检测未感染和VSV感染的PBL体外产生的细胞因子:TNF-α、IFN-γ、IL-1β、IL-10。与对照组相比,患有AD的女性比患有AD的男性表现出更低的平均先天免疫水平。AD男性的TNF-α、IL-10和IL-1β的平均水平高于AD女性,而在对照组中没有观察到这种变化。AD患者的IFN-γ水平高于对照组。与对照组相比,AD的PBL在病毒感染后没有增加IFN-γ的产生。与患有AD的男性相比,患有AD的女性白细胞对病毒感染的反应较弱,细胞因子的产生也少得多。将性别视为AD的一个生物学变量很重要,因为它有望促进我们对AD病理机制的理解,并可能成为未来治疗AD的基础。
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引用次数: 1
Transcriptome Studies in Lupus Nephritis 狼疮性肾炎的转录组研究
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-04-25 DOI: 10.1007/s00005-022-00651-y
Marta E. Alarcón-Riquelme

The present review is aimed at describing the main works that have used gene expression to analyze tissue kidney samples of lupus nephritis patients. Most studies used the gene expression arrays, which enormously advanced our knowledge on the possible mechanisms behind lupus nephritis. However, using bulk gene expression platforms, either as arrays, or as sequencing of RNA is not enough to go into detail of the cells and their molecular patterns and single cell mechanisms of disease. More recently, the first single cell RNA Sequencing study was published and this will also be discussed in the context of lupus nephritis. Single cell RNA sequencing allows to retrieve the genes expressed in each cell in the tissue of interest or in blood. In this context, the results of such studies give us a first glimpse of how a lupus nephritis kidney looks like, but much is still to be done to understand the changes that occur with treatment or with the different pathological subtypes of lupus nephritis and their cellular content.

本综述旨在描述利用基因表达分析狼疮性肾炎患者肾组织样本的主要工作。大多数研究都使用了基因表达阵列,这极大地提高了我们对狼疮性肾炎可能机制的认识。然而,使用大量基因表达平台,无论是作为阵列还是作为RNA测序,都不足以深入了解细胞及其分子模式和单细胞疾病机制的细节。最近,发表了第一项单细胞RNA测序研究,这也将在狼疮性肾炎的背景下进行讨论。单细胞RNA测序可以检索感兴趣组织或血液中每个细胞中表达的基因。在这种情况下,这些研究的结果让我们第一次看到了狼疮性肾炎肾脏的样子,但要了解狼疮性肾炎的治疗或不同病理亚型及其细胞含量的变化,还有很多工作要做。
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引用次数: 0
Hydroxychloroquine Therapy and Serum Immunoglobulin Levels in Women with IgG Subclass Deficiency and Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis: A Retrospective Study 羟氯喹治疗和血清免疫球蛋白水平在妇女IgG亚类缺乏和系统性红斑狼疮,Sjögren综合征,类风湿关节炎:回顾性研究
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-04-11 DOI: 10.1007/s00005-022-00652-x
James C. Barton, J. Clayborn Barton, Luigi F. Bertoli

Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found no report of Ig levels of women with IgG subclass deficiency (IgGSD) and systemic lupus erythematosus (SLE), SS, or RA treated with HCQ. We retrospectively evaluated IgG, IgG subclass, IgA, and IgM levels and other characteristics of women at IgGSD diagnosis who did and did not take HCQ for SLE, SS, or RA. There were 132 women (48 subnormal IgG1 only, 49 combined subnormal IgG1/IgG3, and 35 subnormal IgG3 only). Mean age was 49 ± 13 years. Twenty-two women with SLE, SS, RA, or combination thereof reported HCQ ≥ 200 mg/day ≥ 6 months. In each IgGSD subtype, median Ig levels of women who took HCQ were not significantly lower than those of women who did not take HCQ. Women with combined subnormal IgG1/IgG3 who took HCQ had greater median IgG2 than women who did not take HCQ (4.89 g/L (range 4.43, 4.94) vs. 2.57 g/L (1.21, 6.44), respectively; p = 0.0123). Regressions on IgG1, IgG2, and IgG3 revealed positive associations with HCQ therapy (p = 0.0043, 0.0037, and 0.0139, respectively). There were no significant Ig associations with age, SLE, SS, or RA as independent variables. HCQ therapy of SLE, SS, or RA in women with IgGSD was not associated with significantly lower IgG, IgG subclass, IgA, or IgM levels. IgG1, IgG2, and IgG3 were positively associated with HCQ therapy, after adjustment for other variables.

在先前的研究中,羟氯喹(HCQ)治疗可降低Sjögren综合征(SS)和类风湿性关节炎(RA)患者的免疫球蛋白(Ig)水平。我们没有发现IgG亚类缺乏症(IgGSD)和系统性红斑狼疮(SLE)、SS或RA接受HCQ治疗的女性IgG水平的报告。我们回顾性地评估了IgG、IgG亚类、IgA和IgM水平以及诊断为IgGSD的女性在SLE、SS或RA中使用和未使用HCQ的其他特征。132名女性(48名仅IgG1亚正常,49名IgG1/IgG3合并亚正常,35名仅IgG3亚正常)。平均年龄49±13岁。22名SLE、SS、RA或合并患者报告HCQ≥200mg /天≥6个月。在每一种IgGSD亚型中,服用HCQ的女性的平均Ig水平并不显著低于未服用HCQ的女性。合并IgG1/IgG3不正常的妇女服用HCQ的IgG2中位数高于未服用HCQ的妇女(分别为4.89 g/L(范围4.43,4.94)和2.57 g/L(范围1.21,6.44);p = 0.0123)。IgG1、IgG2和IgG3的回归显示与HCQ治疗呈正相关(p分别= 0.0043、0.0037和0.0139)。Ig与年龄、SLE、SS或RA作为自变量无显著关联。患有IgGSD的女性SLE、SS或RA的HCQ治疗与IgG、IgG亚类、IgA或IgM水平的显著降低无关。在校正其他变量后,IgG1、IgG2和IgG3与HCQ治疗呈正相关。
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引用次数: 0
Hydroxychloroquine Therapy and Serum Immunoglobulin Levels in Women with IgG Subclass Deficiency and Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis: A Retrospective Study 羟氯喹治疗和血清免疫球蛋白水平在妇女IgG亚类缺乏和系统性红斑狼疮,Sjögren综合征,类风湿关节炎:回顾性研究
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-04-11 DOI: 10.1007/s00005-022-00652-x
J. Barton, J. Barton, L. Bertoli
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引用次数: 0
Preliminary Results for Personalized Therapy in Pregnant Women with Polycystic Ovary Syndrome During the COVID-19 Pandemic COVID-19大流行期间孕妇多囊卵巢综合征个体化治疗的初步结果
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2022-03-24 DOI: 10.1007/s00005-022-00650-z
Małgorzata Jerzak, Monika Szafarowska

Increased androgen level, hyperinsulinemia, diabetes, impaired fibrinolysis, obesity, hypertension, chronic inflammation, abnormal immune response to infections and hyperhomocysteinemia are the most common abnormalities related to polycystic ovary syndrome (PCOS) women and are the factors predisposing to the severe course of COVID-19. The SARS-Cov-2 infection during pregnancy is associated with an increased risk of complications (spontaneous abortion), similar to those in PCOS. The treatment of PCOS pregnant women with a history of fertility failures raises many doubts, especially during the COVID pandemic. However, due to the increasing incidence of infections among reproductive people and the potentially more serious course in pregnant women, numerous questions about the safety and effectiveness of the treatment are still very current. In our study we presented a series of cases of recurrent miscarriages or recurrent implantation failure PCOS pregnant women with confirmed COVID-19. The diagnosis of infertility confirmed the presence of plasminogen activator inhibitor type 1 and/or 5,10-methylenetetrahydrofolate reductase polymorphisms in each of them. Moreover, some of the women presented immune dysfunction associated with infertility. We have described the personalized treatments of each pregnant patient included: metformin, enoxaparin and tacrolimus. The treatment applied had the expected effect, supporting the implantation processes. Furthermore, despite the ambiguous data according to immunological therapy of infertile women during the COVID pandemic, we observed a mild or asymptomatic COVID-19 course and we noticed no pregnancy complications.

雄激素水平升高、高胰岛素血症、糖尿病、纤维蛋白溶解功能受损、肥胖、高血压、慢性炎症、对感染的异常免疫反应和高同型半胱氨酸血症是与多囊卵巢综合征(PCOS)女性相关的最常见异常,是导致COVID-19严重病程的因素。怀孕期间感染SARS-Cov-2与并发症(自然流产)的风险增加有关,类似于多囊卵巢综合征。有生育失败史的多囊卵巢综合征孕妇的治疗引起了许多疑问,特别是在COVID大流行期间。然而,由于在生育人群中感染的发生率不断增加,并且孕妇可能出现更严重的病程,关于治疗的安全性和有效性的许多问题仍然非常紧迫。在我们的研究中,我们报告了一系列确诊为COVID-19的PCOS孕妇复发性流产或复发性植入失败的病例。不孕症的诊断证实了纤溶酶原激活物抑制剂1型和/或5,10-亚甲基四氢叶酸还原酶多态性的存在。此外,一些妇女出现与不孕有关的免疫功能障碍。我们描述了每个孕妇的个性化治疗包括:二甲双胍,依诺肝素和他克莫司。所采用的治疗方法达到了预期的效果,支持了种植过程。此外,尽管关于COVID大流行期间不孕妇女免疫治疗的数据不明确,但我们观察到轻度或无症状的COVID-19病程,并且没有发现妊娠并发症。
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Archivum Immunologiae et Therapiae Experimentalis
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