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Hematopoietic stem cell transplantation in a patient with activated phosphoinositide 3‑kinase δ syndrome: A case report and literature review 活化磷酸肌酸 3- 激酶 δ 综合征患者的造血干细胞移植:病例报告与文献综述
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-12-21 DOI: 10.5114/ceji.2023.133949
Mateusz P. Łyżwa, Karolina Kędziora, Natalia Kałamarz, Jowita Frączkiewicz, Anna Panasiuk, Joanna Owoc-Lempach, Barbara Piątosa, Marcin Hennig, Ninela Irga-Jaworska, Krzysztof Kałwak
Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described disease characterized by recurrent infections, lymphoproliferation with a high risk of malignancy, early-onset cytopenia, and a propensity for autoimmune diseases. Hematopoietic stem cell transplantation (HSCT) has proven to be an effective treatment method; however, the recovery process after HSCT is prolonged and accompanied by complications. In this study, we present the case of a patient with APDS type 1. Despite showing signs of immunodeficiency at the age of 6 months, it took almost 6 years to reach a definitive diagnosis. The patient experienced recurrent infections, often accompanied by anemia requiring transfusions, and multifocal nonmalignant lymphoproliferation. Only after receiving the appropriate diagnosis was it possible to implement proper and accurate treatment. HSCT was performed when the patient was 6 years old, leading to significant improvement in his condition. At the 17-month post-HSCT follow-up, the boy is asymptomatic and in good general health, although close monitoring continues due to mixed chimerism and delayed humoral immune recovery. Applying HSCT before the patient develops malignancy contributes to expanding the use of HSCT as a treatment option for APDS type 1.
活化磷酸肌酸 3- 激酶δ综合征(APDS)是最近描述的一种疾病,其特点是反复感染、淋巴细胞增生(恶性肿瘤风险高)、早发全血细胞减少症和自身免疫性疾病倾向。造血干细胞移植(HSCT)已被证明是一种有效的治疗方法;然而,造血干细胞移植后的恢复过程漫长且伴有并发症。在本研究中,我们介绍了一名 APDS 1 型患者的病例。尽管患者在 6 个月大时就出现了免疫缺陷的症状,但经过近 6 年的时间才得到明确诊断。患者反复感染,经常伴有贫血,需要输血,并出现多灶性非恶性淋巴细胞增生。只有在得到适当的诊断后,才有可能实施适当而准确的治疗。患者在 6 岁时接受了造血干细胞移植,病情明显好转。在造血干细胞移植后 17 个月的随访中,男孩没有任何症状,总体健康状况良好,但由于混合嵌合体和体液免疫恢复延迟,仍需继续密切监测。在患者发生恶性肿瘤之前进行造血干细胞移植,有助于扩大造血干细胞移植在治疗 APDS 1 型中的应用。
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引用次数: 0
The role of inflammatory and remodelling biomarkers in patients with non-small cell lung cancer 炎症和重塑生物标志物在非小细胞肺癌患者中的作用
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-12-13 DOI: 10.5114/ceji.2023.133725
Hemn Abdalla Omer, Christer Janson, Kawa Amin
Introduction:
Biomarkers play a crucial role in evaluating the prognosis, diagnosis, and monitoring of non-small cell lung cancer (NSCLC). The aim of this study was to compare the levels of inflammatory and remodelling biomarkers among patients with NSCLC and healthy controls (HCs) and to investigate the correlation between these biomarkers.

Material and methods:
Blood samples were taken from 93 NSCLC and 84 HCs. Each sample was analysed for the inflammatory biomarkers transforming growth factor β1 (TGF-β1), mothers against decapentaplegic homolog 2 (SMAD2) and the remodelling biomarkers Wingless-related integration site (Wnt3a) and β-catenin (CTNN-β1).

Results:
The patients with NSCLC had significantly higher levels of all the measured biomarkers. In the NSCLC patients, TGF-β1 correlated significantly with SMAD2 (r = 0.34, p = 0.0008), Wnt3a (r = 0.328, p = 0.0013), and CTNN-β1 levels (r = 0.30, p = 0.004). SMAD2 correlated significantly with CTNN β1 (r = 0.546, p = 0.0001) and Wnt3a (r = 0.598, p = 0.0001). CTNN-β1 level also correlated with the level of Wnt3a (r = 0.61, p = 0.0001). No correlation was found between biomarkers and symptom scores.

Discussion:
In this study, patients with NSCLC had higher inflammatory and remodelling biomarker levels than HCs. In the NSCLC, there were significant associations between inflammatory and remodelling biomarkers. This indicates that measuring biomarkers could be valuable in the workup of NSCLC patients.

Conclusions:
Our investigation showed that inflammatory and remodelling biomarkers might play a role in future immunologic response and pharmacologically targeted NSCLC therapy.

导言:生物标志物在非小细胞肺癌(NSCLC)的预后评估、诊断和监测中发挥着至关重要的作用。本研究旨在比较非小细胞肺癌患者和健康对照组(HCs)的炎症和重塑生物标志物水平,并研究这些生物标志物之间的相关性。每个样本都分析了炎症生物标志物转化生长因子β1(TGF-β1)、抗截瘫同源母细胞2(SMAD2)以及重塑生物标志物Wingless相关整合位点(Wnt3a)和β-catenin(CTNN-β1)。在 NSCLC 患者中,TGF-β1 与 SMAD2(r = 0.34,p = 0.0008)、Wnt3a(r = 0.328,p = 0.0013)和 CTNN-β1 水平(r = 0.30,p = 0.004)显著相关。SMAD2 与 CTNN β1(r = 0.546,p = 0.0001)和 Wnt3a(r = 0.598,p = 0.0001)明显相关。CTNN-β1 的水平也与 Wnt3a 的水平相关(r = 0.61,p = 0.0001)。讨论:在本研究中,NSCLC 患者的炎症和重塑生物标志物水平高于 HCs。在 NSCLC 患者中,炎症和重塑生物标志物之间存在显著关联。结论:我们的研究表明,炎症和重塑生物标志物可能在未来的免疫反应和药物靶向治疗中发挥作用。
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引用次数: 0
Association of human leukocyte antigen class II alleles with epithelial cell apoptosis and extracellular matrix production in acute COVID-19 人类白细胞抗原 II 类等位基因与急性 COVID-19 上皮细胞凋亡和细胞外基质生成的关系
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-12-12 DOI: 10.5114/ceji.2023.133684
Ieva Vanaga, Oksana Kolesova, Aleksandrs Kolesovs, Gunta Sture, Elvira Hagina, Jelena Storozenko, Liene Nikitina-Zake, Ludmila Viksna
Introduction:
Pathogenic mechanisms and long-term consequences of COVID-19 require attention in studies on SARS-CoV-2. The association of the severity of COVID-19 with genetic factors, such as human leukocyte antigen (HLA) genes, remains underexplored. Our study assessed the relationships between HLA class II alleles and COVID-19 severity and blood-based indicators of systemic inflammation and organ damage, serum markers of epithelial cell apoptosis such as caspase-cleaved CK18 fragment M30 (CK18-M30) and the extracellular matrix product hyaluronic acid (HA).

Material and methods:
The study included 101 hospitalized COVID-19 patients (mean age 60 ±14 years). Clinical tests were performed at admission to the hospital. The levels of CK18-M30 and HA were detected in serum by enzyme-linked immunosorbent assay (ELISA). HLA typing was performed in HLA-DRB1, -DQA1, and -DQB1 loci by the polymerase chain reaction with low-resolution sequence-specific primers.

Results:
Sixty-one patients had a non-severe and 40 had a severe or critical disease course (following the WHO definition). The severity was associated with older age, male gender, higher HA, CK18-M30, and some indicators of inflammation. Despite the lack of direct association between HLA alleles and the severity of COVID-19, the presence of HLA-DRB1*04 and 12 alleles in the genotype was associated with lowered or elevated HA, respectively. The HLA-DQB1*03:01 allele was associated with lowered CK18-M30, aspartate aminotransferase, and ferritin. In addition, HLA-DQB1*06:01 was associated with elevated alanine aminotransferase.

Conclusions:
Associations of HLA class II alleles with markers of epithelial cell apoptosis and extracellular matrix production indirectly support the influence of HLA genes on acute COVID-19 severity.

导言:在对 SARS-CoV-2 进行研究时,需要关注 COVID-19 的致病机制和长期后果。COVID-19的严重程度与遗传因素(如人类白细胞抗原(HLA)基因)之间的关系仍未得到充分探讨。我们的研究评估了HLA II类等位基因与COVID-19严重程度之间的关系,以及基于血液的全身炎症和器官损伤指标、上皮细胞凋亡血清标志物(如Caspase裂解的CK18片段M30(CK18-M30)和细胞外基质产物透明质酸(HA))之间的关系。入院时进行了临床检测。通过酶联免疫吸附试验(ELISA)检测血清中 CK18-M30 和 HA 的水平。结果:61 名患者的病程不严重,40 名患者的病程严重或危重(根据世界卫生组织的定义)。严重程度与年龄、性别、较高的 HA、CK18-M30 和一些炎症指标有关。尽管 HLA 等位基因与 COVID-19 的严重程度没有直接联系,但基因型中存在 HLA-DRB1*04 和 12 等位基因分别与 HA 降低或升高有关。HLA-DQB1*03:01等位基因与CK18-M30、天冬氨酸氨基转移酶和铁蛋白的降低有关。结论:HLA II类等位基因与上皮细胞凋亡和细胞外基质生成标记物的相关性间接支持了HLA基因对急性COVID-19严重程度的影响。
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引用次数: 0
Immunotherapy of B cell lymphoma with CD22-redirected CAR NK-92 cells. cd22重定向CAR - NK-92细胞对B细胞淋巴瘤的免疫治疗
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.126672
Xiaopeng Tian, Ruixi Zhang, Huimin Qin, Xiangru Shi, Wenhui Qi, Dongpeng Jiang, Tingting Zhu, Aining Sun

Introduction: Chimeric antigen receptor (CAR)-NK cells are considered safer than CAR-T cells due to their short lifetime and production of lower toxicity cytokines. By virtue of unlimited proliferative ability in vitro, NK-92 cells could be utilized as the source for CAR-engineered NK cells. CD22 is highly expressed in B cell lymphoma. The goal of our study was to determine whether CD22 could become an alternative target for CAR-NK-92 therapy against B cell lymphoma.

Material and methods: We first generated m971-BBZ NK-92 that expressed a CAR for binding CD22 in vitro. The expression of CAR was assessed by flow cytometric analysis as well as immunoblotting. The cytotoxicity of the m971-BBZ NK-92 cells towards target lymphoma cells was determined by the luciferase-based cytolysis assay. The production of cytokines in CAR NK-92 cells in response to target cells was evaluated by ELISA assay. Lastly, the cytolytic effect was evaluated by the cytolysis assay mentioned above following irradiation. The level of inhibitory receptor of CAR-expressing cells was assessed by flow cytometry.

Results: CD22-specific CAR was expressed on m971-BBZ NK-92 cells successfully. m971-BBZ NK-92 cells efficiently lysed CD22-expressing lymphoma cells and produced large amounts of cytokines after coculture with target cells. Meanwhile, irradiation did not apparently influence the cytotoxicity of m971-BBZ NK-92 cells. Inhibitory receptor detection exhibited a lower level of PD-1 in m971-BBZ NK-92 cells than FMC-63 BBZ T cells after repeated antigen stimulation.

Conclusions: Our data show that adoptive transfer of m971-BBZ NK-92 could serve as a promising strategy for immunotherapy of B cell lymphoma.

嵌合抗原受体(CAR)-NK细胞被认为比CAR- t细胞更安全,因为它们寿命短,产生的毒性较低的细胞因子。NK-92细胞在体外具有无限的增殖能力,可以作为car工程NK细胞的来源。CD22在B细胞淋巴瘤中高表达。我们研究的目的是确定CD22是否可以成为CAR-NK-92治疗B细胞淋巴瘤的替代靶点。材料和方法:我们首先在体外生成了表达CAR结合CD22的m971-BBZ NK-92。通过流式细胞分析和免疫印迹法检测CAR的表达。采用荧光素酶细胞溶解法测定m971-BBZ NK-92细胞对靶淋巴瘤细胞的细胞毒性。ELISA法检测CAR - NK-92细胞对靶细胞产生的细胞因子。最后,通过上述照射后的细胞溶解试验来评价细胞溶解作用。流式细胞术检测car表达细胞的抑制受体水平。结果:cd22特异性CAR在m971-BBZ NK-92细胞上成功表达。m971-BBZ NK-92细胞与靶细胞共培养后,能高效裂解表达cd22的淋巴瘤细胞,并产生大量细胞因子。同时,辐照对m971-BBZ NK-92细胞的细胞毒性无明显影响。抑制受体检测显示,经过多次抗原刺激后,m971-BBZ NK-92细胞中的PD-1水平低于FMC-63 BBZ T细胞。结论:我们的数据表明,过继性转移m971-BBZ NK-92可能是一种有希望的B细胞淋巴瘤免疫治疗策略。
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引用次数: 0
Newly diagnosed seropositive rheumatoid arthritis in a 52-year-old man superimposed on long-standing ankylosing spondylitis during secukinumab treatment 新诊断的血清阳性类风湿关节炎在52岁的男性叠加长期强直性脊柱炎在secukinumab治疗期间
4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.132066
Jaroslaw Nowakowski, Anna Tomoń, Dorota Telesińska-Jasiówka
rheumatoid arthritis (ra) and ankylosing spondylitis (as) are severe chronic inflammatory joint diseases with different immune-mediated mechanisms playing a role in their pathogenesis. rheumatoid arthritis is an erosive arthritis of peripheral joints and as is a spondyloarthropathy affecting mainly sacroiliac and spinal joints leading to excessive bone formation and ankylosis. The coexistence of rA and As in the same patient is rare. Presented here is a 52-year-old patient with long-standing As with bilateral ankylosis of sacroiliac joints who developed peripheral symmetric polyarthritis while being treated with the interleukin 17 inhibitor secukinumab introduced due to secondary inefficacy of the tu - mor necrosis a inhibitor etanercept. He was finally diagnosed with seropositive rA coexisting with As and treatment was changed to the Janus kinase inhibitor tofacitinib. eventually, remission was sustained with use of the interleukin 6 inhibitor tocilizumab. This is the first case of rA developing during anti-interleukin 17 therapy. Although tocilizumab lacks efficaciousness in As, in this case therapy was succesful as the rA-driving cytokine mechanism possibly prevailed.
{"title":"Newly diagnosed seropositive rheumatoid arthritis in a 52-year-old man superimposed on long-standing ankylosing spondylitis during secukinumab treatment","authors":"Jaroslaw Nowakowski, Anna Tomoń, Dorota Telesińska-Jasiówka","doi":"10.5114/ceji.2023.132066","DOIUrl":"https://doi.org/10.5114/ceji.2023.132066","url":null,"abstract":"rheumatoid arthritis (ra) and ankylosing spondylitis (as) are severe chronic inflammatory joint diseases with different immune-mediated mechanisms playing a role in their pathogenesis. rheumatoid arthritis is an erosive arthritis of peripheral joints and as is a spondyloarthropathy affecting mainly sacroiliac and spinal joints leading to excessive bone formation and ankylosis. The coexistence of rA and As in the same patient is rare. Presented here is a 52-year-old patient with long-standing As with bilateral ankylosis of sacroiliac joints who developed peripheral symmetric polyarthritis while being treated with the interleukin 17 inhibitor secukinumab introduced due to secondary inefficacy of the tu - mor necrosis a inhibitor etanercept. He was finally diagnosed with seropositive rA coexisting with As and treatment was changed to the Janus kinase inhibitor tofacitinib. eventually, remission was sustained with use of the interleukin 6 inhibitor tocilizumab. This is the first case of rA developing during anti-interleukin 17 therapy. Although tocilizumab lacks efficaciousness in As, in this case therapy was succesful as the rA-driving cytokine mechanism possibly prevailed.","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135059027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trigeminal neuralgia occurring after the third dose of Pfizer BioNTech COVID-19 vaccine. Complication or coincidence? An illustrative case report and literature review. 三叉神经痛发生在第三剂辉瑞BioNTech COVID-19疫苗后。复杂还是巧合?一篇说明性病例报告及文献回顾。
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.125309
Kacper Chrostowski, Michał Piasecki, Joanna Bielewicz

The coronavirus disease 2019 pandemic is an ongoing concern for medical care worldwide. Since its emergence, multiple COVID-19 vaccines have been designed, allowing for more effective control of the pandemic. COVID-19 vaccines, like any other form of medical intervention, may cause adverse and unforeseen side effects, varying in frequency and severity. Determining a correlation between the occurring symptoms and the vaccination is often a challenging task, requiring multiple data sources and reported cases. So far, there have been multiple reports of trigeminal neuralgia developing after COVID-19 vaccination. A 36-year-old woman was admitted to the Emergency Ward due to chronic pain attacks in the left side of her face. The pain appeared two months ago, on the day following the vaccination using the third dose of the Pfizer BioNTech COVID-19 vaccine. At the Neurology Department she was diagnosed with trigeminal neuralgia. Based on the lack of any obvious causes, relation to the vaccination, and other similar reports, we assumed that the trigeminal neuralgia was a complication of the vaccination. Hospital treatment consisted of oxcarbazepine, dexamethasone and pregabalin. Treatment was successful, with transient episodes of exacerbation. Six months after the onset of the disorder the patient remains without pain. We believe that the presented case supports the possibility of trigeminal neuralgia occurring in relation to the Pfizer BioNTech COVID-19 vaccine administration. Additional reports may further contribute to establishing a certain link.

2019年冠状病毒病大流行是全球医疗保健持续关注的问题。自出现以来,已设计出多种COVID-19疫苗,从而能够更有效地控制大流行。与任何其他形式的医疗干预一样,COVID-19疫苗可能会导致不良和不可预见的副作用,其频率和严重程度各不相同。确定出现的症状与疫苗接种之间的相关性往往是一项具有挑战性的任务,需要多个数据来源和报告的病例。到目前为止,已有多例报告显示,接种COVID-19疫苗后出现三叉神经痛。一名36岁妇女因左脸慢性疼痛发作被送入急诊室。这种疼痛出现在两个月前,即注射第三剂辉瑞BioNTech新冠疫苗的第二天。在神经科,她被诊断为三叉神经痛。基于缺乏任何明显的原因,与疫苗接种有关,以及其他类似的报告,我们假设三叉神经痛是疫苗接种的并发症。住院治疗包括奥卡西平、地塞米松和普瑞巴林。治疗是成功的,有短暂的发作。发病6个月后,病人仍无疼痛。我们认为,本病例支持与辉瑞BioNTech COVID-19疫苗接种有关的三叉神经痛发生的可能性。其他报告可能进一步有助于建立某种联系。
{"title":"Trigeminal neuralgia occurring after the third dose of Pfizer BioNTech COVID-19 vaccine. Complication or coincidence? An illustrative case report and literature review.","authors":"Kacper Chrostowski,&nbsp;Michał Piasecki,&nbsp;Joanna Bielewicz","doi":"10.5114/ceji.2023.125309","DOIUrl":"https://doi.org/10.5114/ceji.2023.125309","url":null,"abstract":"<p><p>The coronavirus disease 2019 pandemic is an ongoing concern for medical care worldwide. Since its emergence, multiple COVID-19 vaccines have been designed, allowing for more effective control of the pandemic. COVID-19 vaccines, like any other form of medical intervention, may cause adverse and unforeseen side effects, varying in frequency and severity. Determining a correlation between the occurring symptoms and the vaccination is often a challenging task, requiring multiple data sources and reported cases. So far, there have been multiple reports of trigeminal neuralgia developing after COVID-19 vaccination. A 36-year-old woman was admitted to the Emergency Ward due to chronic pain attacks in the left side of her face. The pain appeared two months ago, on the day following the vaccination using the third dose of the Pfizer BioNTech COVID-19 vaccine. At the Neurology Department she was diagnosed with trigeminal neuralgia. Based on the lack of any obvious causes, relation to the vaccination, and other similar reports, we assumed that the trigeminal neuralgia was a complication of the vaccination. Hospital treatment consisted of oxcarbazepine, dexamethasone and pregabalin. Treatment was successful, with transient episodes of exacerbation. Six months after the onset of the disorder the patient remains without pain. We believe that the presented case supports the possibility of trigeminal neuralgia occurring in relation to the Pfizer BioNTech COVID-19 vaccine administration. Additional reports may further contribute to establishing a certain link.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"48 1","pages":"75-80"},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/14/CEJI-48-50183.PMC10189574.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9930538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The role of monocytes in malaria infection. 单核细胞在疟疾感染中的作用。
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.126650
Keh Min Xuan, Nurhidanatasha Abu Bakar, Khairul Mohd Fadzli Mustaffa, Maryam Azlan

Malaria remains one of the most common human infections worldwide. In endemic areas, malaria is a leading cause of morbidity and mortality and it imposes significant socioeconomic burdens on the people affected. Monocytes are part of the immune system controlling parasite burden and protecting the host against malaria infection. Monocytes play their protective roles against malaria via phagocytosis, cytokine production and antigen presentation. Though monocytes are crucial for clearance of malaria infection, they have also been shown to cause adverse clinical outcomes. In this review, we discuss recent findings regarding the role of monocytes in malaria via mechanisms such as parasite detection and clearance, pro-inflammatory activities, and activation of other immune components. We also highlight the role of different monocyte subsets, and other myeloid cells that are involved in malaria infection. However, more investigations are required in order to explore the exact roles of these monocytes in malaria infection.

疟疾仍然是世界上最常见的人类传染病之一。在流行地区,疟疾是发病和死亡的主要原因,并给受影响的人造成重大的社会经济负担。单核细胞是控制寄生虫负担和保护宿主免受疟疾感染的免疫系统的一部分。单核细胞通过吞噬作用、细胞因子产生和抗原呈递发挥抗疟疾的保护作用。虽然单核细胞对清除疟疾感染至关重要,但它们也被证明会导致不良的临床结果。在这篇综述中,我们讨论了关于单核细胞在疟疾中的作用的最新发现,如寄生虫检测和清除、促炎活性和其他免疫成分的激活。我们还强调了不同的单核细胞亚群和其他参与疟疾感染的骨髓细胞的作用。然而,为了探索这些单核细胞在疟疾感染中的确切作用,还需要更多的研究。
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引用次数: 0
Molecular regulatory mechanism of LILRB4 in the immune response. LILRB4在免疫应答中的分子调控机制。
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.125238
Haiyin Liu, Jun Yang, Jing Zhang, Peiyue Zhang, Mengting Zhang, Chaojun Yang, Li Liu, Cuiyuan Huang, Wei Wang, Yuhong Zhai, Jian Yang

Immune diseases are caused by the imbalance of immune regulation. This imbalance is regulated by many factors, both negative and positive. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is a member of leukocyte immunoglobulin-like receptors (LILRs). LILRs are expressed constitutively on the surface of multiple immune cells which associate with membrane adaptors to signal through multi- ple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or immunoreceptor tyro-sine-based activation motifs (ITAMs). Through ITIM, LILRB4 could recruit the src homology domain type-2-containing tyrosine phosphatase 1 or 2 (SHP-1 or SHP-2) into the cell membrane. In addition, many factors can induce the expression of LILRB4, such as vitamin D, interferon and so on. Studies have demonstrated that LILRB4 had a negative regulatory role in various of immune diseases. The present review intends to expound the structure and function of LILRB4, as well as its regulators and receptors in the immune cells, so as to provide a theoretical basis for immune disease therapy.

免疫性疾病是由免疫调节失衡引起的。这种不平衡受到许多因素的调节,既有消极的因素,也有积极的因素。白细胞免疫球蛋白样受体B4 (LILRB4)是白细胞免疫球蛋白样受体(LILRs)的一个成员。lilr在多种免疫细胞表面组成性地表达,这些细胞通过多种细胞质免疫受体酪氨酸抑制基序(ITIMs)或免疫受体酪氨酸激活基序(ITAMs)与膜受体结合,发出信号。LILRB4通过ITIM将src同源结构域2型酪氨酸磷酸酶1或2 (SHP-1或SHP-2)募集到细胞膜内。此外,许多因素可以诱导LILRB4的表达,如维生素D、干扰素等。研究表明,LILRB4在多种免疫疾病中具有负调控作用。本文拟阐述LILRB4的结构和功能,以及其在免疫细胞中的调节因子和受体,为免疫疾病的治疗提供理论依据。
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引用次数: 0
A rare cause of steroid-resistant nephrotic syndrome - a case report. 类固醇抵抗性肾病综合征的罕见病因- 1例报告。
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.127534
Paulina Kuran, Emilia Platos, Małgorzata Mizerska-Wasiak, Małgorzata Pańczyk-Tomaszewska

Steroid resistance is a common condition occurring in children with nephrotic syndrome. Until now, over 50 genes involved in steroid-resistant nephrotic syndrome (SRNS) pathogenesis have been identified, among which the most prevalent are NPHS1, NPHS2, CD2AP, and PTPRO. The patterns of inheritance of SRNS are autosomal recessive, autosomal dominant, or mitochondrial, and tissues of those patients show focal segmental glomerulosclerosis (FSGS) signs in histopathological image analysis. We present a case of a 6-year-old girl who was admitted to the pediatric nephrology department due to nephrotic range proteinuria and edema of the lower leg. We started therapy with prednisone at a dose of 45 mg (60 mg/m2), enalapril as a nephroprotection, and antihistamines as an additional treatment. During in-patient treatment, we detected increased blood pressure. Due to persistent proteinuria in spite of 6-week treatment with steroids at the maximal dose, we confirmed disease resistance to steroids. Additionally, FSGS signs were confirmed in kidney biopsy samples. After genetic screening for SRNS and detection of the rare gene mutation NUP93 we reduced prednisone but maintained nephroprotective treatment and administered cyclosporin A. The girl remains currently under the care of nephrologists with normal arterial blood pressure, trace proteinuria in follow-up examination, and normal kidney function. NUP93 mutation is extremely rare; therefore few cases have been described to date. The onset of the symptoms in all pediatric patients appeared before the age of 8 and they developed end stage kidney disease (ESKD). They might manifest symptoms from the other systems.

类固醇抵抗是儿童肾病综合征的常见病。到目前为止,已经鉴定出50多个与激素抵抗性肾病综合征(SRNS)发病相关的基因,其中最常见的是NPHS1、NPHS2、CD2AP和PTPRO。SRNS的遗传模式为常染色体隐性遗传、常染色体显性遗传或线粒体遗传,这些患者的组织病理图像分析显示局灶节段性肾小球硬化(FSGS)征象。我们报告一例6岁女童因肾病范围蛋白尿及下肢水肿而入院儿科肾脏病科。我们开始使用强的松治疗,剂量为45mg (60mg /m2),依那普利作为肾保护,抗组胺药作为附加治疗。在住院治疗期间,我们检测到血压升高。尽管用最大剂量的类固醇治疗了6周,但由于持续的蛋白尿,我们证实了对类固醇的疾病抵抗。此外,肾活检样本也证实了FSGS征象。经SRNS基因筛查和罕见基因突变NUP93检测后,我们减少了强的松治疗,但仍维持肾保护治疗并给予环孢素a。女孩目前仍在肾科医生的护理下,动脉血压正常,随访检查微量蛋白尿,肾功能正常。NUP93突变极为罕见;因此,迄今为止很少有病例被描述。所有儿童患者的症状均出现在8岁之前,并发展为终末期肾病(ESKD)。他们可能会出现其他系统的症状。
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引用次数: 1
Effects of theophylline combined with inhaled corticosteroids on patients with moderate and severe asthma and changes of T lymphocyte subsets in peripheral blood. 茶碱联合吸入皮质类固醇对中重度哮喘患者外周血T淋巴细胞亚群的影响。
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.5114/ceji.2023.127843
Xiaozhen Cai, Rong Rong, Yidan Huang, Xiaowen Pu, Nanhai Ge

Introduction: Asthma is a common respiratory disease. Theophylline combined with inhaled corticosteroids (ICS) is a promising therapy for asthma. This study explored the therapeutic effects of ICS combined with theophylline on moderate and severe asthma patients and T lymphocyte subsets (CD3+CD8+ T cells) in peripheral blood.

Material and methods: A total of 202 moderate and severe asthma patients were selected, with 101 treated with theophylline combined with ICS and 101 treated with ICS alone as controls. Lung function [forced expiratory volume within 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)] were tested using a spirometer. Asthma symptom control was evaluated by asthma control tests (ACT). The life quality was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). The number and percentage of CD3+ T, CD3+CD4+ T and CD3+CD8+ T cells in peripheral blood mononuclear cells were assessed by flow cytometry. The correlation between CD3+CD8+ T cells and lung function and asthma control of patients after combination therapy was analyzed by Pearson correlation analysis.

Results: Compared with moderate and severe patients treated with ICS alone, theophylline improved the efficacy of ICS. Theophylline combined with ICS decreased IL-4 and IL-6 levels, and CD3+ T and CD3+CD8+ T cell number and percentage. After combined treatment, CD3+ CD8+ T cells in peripheral blood of patients were positively correlated with lung function and negatively correlated with asthma control.

Conclusions: The additional use of theophylline improved the efficacy of corticosteroids in asthma patient treatment and reduced inflammation level and CD3+ T and CD3+CD8+ T cell contents in peripheral blood.

哮喘是一种常见的呼吸系统疾病。茶碱联合吸入皮质类固醇(ICS)是一种很有前途的治疗哮喘的方法。本研究探讨ICS联合茶碱对中重度哮喘患者及外周血T淋巴细胞亚群(CD3+CD8+ T细胞)的治疗效果。材料与方法:选取202例中重度哮喘患者,其中茶碱联合ICS治疗101例,单独ICS治疗101例作为对照。使用肺活量计检测肺功能[1秒内用力呼气量(FEV1)、用力肺活量(FVC)和呼气峰值流量(PEF)]。通过哮喘控制试验(ACT)评估哮喘症状的控制情况。采用哮喘生活质量问卷(AQLQ)评价患者的生活质量。流式细胞术检测外周血单个核细胞中CD3+ T、CD3+CD4+ T和CD3+CD8+ T细胞的数量和百分比。采用Pearson相关分析CD3+CD8+ T细胞与联合治疗后患者肺功能及哮喘控制的相关性。结果:与单用ICS治疗的中重度患者相比,茶碱能提高ICS的疗效。茶碱联合ICS降低IL-4和IL-6水平,降低CD3+ T和CD3+CD8+ T细胞数量和百分比。综合治疗后,患者外周血CD3+ CD8+ T细胞与肺功能呈正相关,与哮喘控制呈负相关。结论:额外使用茶碱可提高皮质类固醇治疗哮喘患者的疗效,降低炎症水平和外周血CD3+ T和CD3+CD8+ T细胞含量。
{"title":"Effects of theophylline combined with inhaled corticosteroids on patients with moderate and severe asthma and changes of T lymphocyte subsets in peripheral blood.","authors":"Xiaozhen Cai,&nbsp;Rong Rong,&nbsp;Yidan Huang,&nbsp;Xiaowen Pu,&nbsp;Nanhai Ge","doi":"10.5114/ceji.2023.127843","DOIUrl":"https://doi.org/10.5114/ceji.2023.127843","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a common respiratory disease. Theophylline combined with inhaled corticosteroids (ICS) is a promising therapy for asthma. This study explored the therapeutic effects of ICS combined with theophylline on moderate and severe asthma patients and T lymphocyte subsets (CD3<sup>+</sup>CD8<sup>+</sup> T cells) in peripheral blood.</p><p><strong>Material and methods: </strong>A total of 202 moderate and severe asthma patients were selected, with 101 treated with theophylline combined with ICS and 101 treated with ICS alone as controls. Lung function [forced expiratory volume within 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)] were tested using a spirometer. Asthma symptom control was evaluated by asthma control tests (ACT). The life quality was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). The number and percentage of CD3<sup>+</sup> T, CD3<sup>+</sup>CD4<sup>+</sup> T and CD3<sup>+</sup>CD8<sup>+</sup> T cells in peripheral blood mononuclear cells were assessed by flow cytometry. The correlation between CD3<sup>+</sup>CD8<sup>+</sup> T cells and lung function and asthma control of patients after combination therapy was analyzed by Pearson correlation analysis.</p><p><strong>Results: </strong>Compared with moderate and severe patients treated with ICS alone, theophylline improved the efficacy of ICS. Theophylline combined with ICS decreased IL-4 and IL-6 levels, and CD3<sup>+</sup> T and CD3<sup>+</sup>CD8<sup>+</sup> T cell number and percentage. After combined treatment, CD3<sup>+</sup> CD8<sup>+</sup> T cells in peripheral blood of patients were positively correlated with lung function and negatively correlated with asthma control.</p><p><strong>Conclusions: </strong>The additional use of theophylline improved the efficacy of corticosteroids in asthma patient treatment and reduced inflammation level and CD3<sup>+</sup> T and CD3<sup>+</sup>CD8<sup>+</sup> T cell contents in peripheral blood.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"48 2","pages":"135-143"},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/09/CEJI-48-50786.PMC10485692.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10220434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Central European Journal of Immunology
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