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Endogenous antibody response to SARS-CoV-2 in patients who received monoclonal antibodies against COVID-19: A systematic review 接受COVID-19单克隆抗体的患者对SARS-CoV-2的内源性抗体反应:一项系统综述
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.08.003
Andrea Lombardi , Cecilia Azzarà , Giulia Renisi , Giulia Viero , Andrea Gori , Alessandra Bandera

Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.

单克隆抗体被动免疫已应用于COVID-19。我们进行了一项系统的文献综述,评估了单克隆抗体治疗患者对SARS-CoV-2的内源性体液免疫反应。在血清阴性患者中使用单克隆抗体导致抗体滴度和对病毒的中和活性降低。
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引用次数: 1
Differential peripheral blood mononuclear cell reactivity against SARS-CoV-2 proteins in naïve and previously infected subjects following COVID-19 vaccination naïve和先前感染的受试者接种COVID-19疫苗后外周血单个核细胞对SARS-CoV-2蛋白的反应性差异
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.11.004
Elizabete Cristina Iseke Bispo , Amandda Évelin Silva-Carvalho , Marielly Reis Resende Sousa , Francisco de Assis Rocha Neves , Juliana Lott Carvalho , Enrique Roberto Arganaraz , Felipe Saldanha-Araujo

The decline in vaccine efficacy and the risk of reinfection by SARS-CoV-2 make new studies important to better characterize the immune response against the virus and its components. Here, we investigated the pattern of activation of T-cells and the expression of inflammatory factors by PBMCs obtained from naïve and previously infected subjects following COVID-19 vaccination, after PBMCs stimulation with S1, RBD, and N-RBD SARS-CoV-2 proteins. PBMCs showed low levels of ACE2 and TMPRSS2 transcripts, which were not modulated by the exposure of these cells to SARS-CoV-2 proteins. Compared to S1 and RBD, N-RBD stimulation showed a greater ability to stimulate T-cell reactivity, according to CD25 and CD69 markers. Interestingly, T-cell reactivity was more pronounced in vaccinated subjects with prior SARS-CoV-2 infection than in vaccinated donors who never had been diagnosed with COVID-19. Finally, N-RBD stimulation promoted greater expression of IL-6 and IFN-γ in PBMCs, which reinforces the greater immunogenic potential of this protein in the vaccinated subjects. These data suggest that PBMCs from previously infected and vaccinated subjects are more reactive than those derived from just vaccinated donors. Moreover, the N-RBD together viral proteins showed a greater stimulatory capacity than S1 and RBD viral proteins.

疫苗效力的下降和SARS-CoV-2再感染的风险使得新的研究对更好地表征针对该病毒及其成分的免疫反应具有重要意义。在这里,我们研究了在接种COVID-19疫苗后,在PBMCs受到S1、RBD和N-RBD SARS-CoV-2蛋白刺激后,从naïve和先前感染的受试者中获得的PBMCs激活t细胞和炎症因子表达的模式。pbmc显示出低水平的ACE2和TMPRSS2转录本,这些转录本不受这些细胞暴露于SARS-CoV-2蛋白的调节。根据CD25和CD69标记,与S1和RBD相比,N-RBD刺激显示出更大的刺激t细胞反应性的能力。有趣的是,在先前感染过SARS-CoV-2的接种疫苗的受试者中,t细胞反应性比从未被诊断为COVID-19的接种疫苗的捐赠者更明显。最后,N-RBD刺激促进了pbmc中IL-6和IFN-γ的表达,这加强了该蛋白在接种受试者中更大的免疫原性潜力。这些数据表明,来自先前感染和接种过疫苗的受试者的pbmc比来自刚刚接种过疫苗的供者的pbmc更具反应性。此外,N-RBD组合病毒蛋白比S1和RBD组合病毒蛋白表现出更强的刺激能力。
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引用次数: 2
Evaluation of the performance of a lateral flow device for quantitative detection of anti-SARS-CoV-2 IgG 抗sars - cov -2 IgG水平流式定量检测装置的性能评价
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.09.001
J.S. Moore , L.J. Robertson , R. Price , G. Curry , J. Farnan , A. Black , M.A. Nesbit , J.A. McLaughlin , T. Moore

Introduction: The AbC-19™ lateral flow immunoassay (LFIA) performance was evaluated on plasma samples from a SARS-CoV-2 vaccination cohort, WHO international standards for anti-SARS-CoV-2 IgG (human), individuals ≥2 weeks from infection of RT-PCR confirmed SARS-CoV-2 genetic variants, as well as microorganism serology.

Methods: Pre-vaccination to three weeks post-booster samples were collected from a cohort of 111 patients (including clinically extremely vulnerable patients) from Northern Ireland. All patients received Oxford-AstraZeneca COVID-19 vaccination for the first and second dose, and Pfizer-BioNTech for the third (first booster). WHO international standards, 15 samples from 2 variants of concern (Delta and Omicron) and cross-reactivity with plasma samples from other microorganism infections were also assessed on AbC-19™.

Results: All 80 (100%) participants sampled post-booster had high positive IgG responses, compared to 38/95 (40%) participants at 6 months post-first vaccination. WHO standard results correlated with information from corresponding biological data sheets, and antibodies to all genetic variants were detected by LFIA. No cross-reactivity was found with exception of one (of five) Dengue virus samples.

Conclusion: These findings suggest BNT162b2 booster vaccination enhanced humoral immunity to SARS-CoV-2 from pre-booster levels, and that this antibody response was detectable by the LFIA. In combination with cross-reactivity, standards and genetic variant results would suggest LFIA may be a cost-effective measure to assess SARS-CoV-2 antibody status.

本研究对来自SARS-CoV-2疫苗接种队列、WHO抗SARS-CoV-2 IgG(人)国际标准、感染RT-PCR确认的SARS-CoV-2遗传变异≥2周的个体以及微生物血清学的血浆样本进行了AbC-19™横向流动免疫测定(LFIA)性能评估。方法:从北爱尔兰111例患者(包括临床极度易感患者)中收集疫苗接种前至加强后三周的样本。所有患者均接种了第一剂和第二剂牛津-阿斯利康COVID-19疫苗,第三剂为辉瑞- biontech疫苗(第一次加强剂)。还用AbC-19™评估了世卫组织国际标准、来自两种关注变体(Delta和Omicron)的15份样本以及与其他微生物感染血浆样本的交叉反应性。结果:与首次接种疫苗6个月后38/95(40%)的参与者相比,所有80名(100%)接种强化疫苗后的参与者都有高阳性IgG反应。世卫组织标准结果与相应生物数据表的信息相关,LFIA检测到所有遗传变异的抗体。除五份登革热病毒样本中的一份外,未发现交叉反应性。结论:上述结果提示BNT162b2加强疫苗接种可增强对SARS-CoV-2的体液免疫,且这种抗体应答可通过LFIA检测到。结合交叉反应性、标准和遗传变异结果,LFIA可能是评估SARS-CoV-2抗体状态的一种具有成本效益的措施。
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引用次数: 0
Appraising SARS-CoV-2 infections after full mRNA COVID-19 vaccination in patients with systemic lupus erythematosus (SLE) 系统性红斑狼疮(SLE)患者全mRNA COVID-19疫苗接种后SARS-CoV-2感染的评价
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.03.002
Anderson Anuforo , Michael Sandhu , Jianghong Yu , Andras Perl

The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects – both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.

2019冠状病毒病(COVID-19)疫苗是抗击冠状病毒2型(SARS-CoV-2)引起的严重急性呼吸系统综合征(SARS-CoV-2)的主要武器。该疫苗可显著降低感染SARS-CoV-2的风险和严重程度。系统性红斑狼疮(SLE)患者需要预防疫苗可预防的疾病,包括COVID-19。由于免疫抑制疗法和多种免疫缺陷,SLE患者的严重感染发生率更高,这两者都能够减弱接种疫苗后的免疫反应。在COVID-19的管理中,已经制定了建议,以指导在接种基于mrna或病毒载体递送的疫苗后调整和/或继续使用免疫抑制疗法,以实现有效的免疫反应。自2021年12月起,单克隆抗体也已上市。在这里,我们报告了三例接种疫苗后感染COVID-19的SLE患者。1例在门诊环境中进行管理,2例需要住院治疗。
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引用次数: 2
Real-life efficacy and safety of mepolizumab for eosinophilic granulomatosis with polyangiitis mepolizumab治疗嗜酸性肉芽肿合并多血管炎的临床疗效和安全性
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.01.002
Giuseppe A. Ramirez , Adriana Cariddi , Silvia Noviello , Corrado Campochiaro , Valentina Canti , Luca Moroni , Mona-Rita Yacoub , Elena M. Baldissera , Enrica P. Bozzolo , Lorenzo Dagna

Little is known about the efficacy and safety of the anti-interleukin 5 monoclonal antibody mepolizumab (MPZ) in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in real-life. We thus evaluated disease activity, damage and disease-related complications in 14 patients with EGPA receiving MPZ for refractory disease for a median time of 16 months in comparison with up to five years before MPZ start. Asthma exacerbation rates, the Birmingham Vasculitis Activity Score and corticosteroid dosage decreased during MPZ (p < 0.001, p < 0.001 and p = 0.001, respectively). Five patients could discontinue prednisone. Infection rates were higher during MPZ (p < 10–6), but no rises in hospitalizations, asthma exacerbations or damage accrual were observed. Real-life data confirm the effectiveness of MPZ in refractory EGPA with active asthma. Higher infections rates are in line with other studies and might be due to relative overreporting secondary to increased visit frequency, although a pharmacological effect could not be ruled out.

抗白细胞介素5单克隆抗体mepolizumab (MPZ)在现实生活中对嗜酸性肉芽肿病合并多血管炎(EGPA)患者的疗效和安全性知之甚少。因此,我们评估了14例接受MPZ治疗难治性疾病的EGPA患者的疾病活动性、损伤和疾病相关并发症,中位时间为16个月,而MPZ治疗前最长为5年。MPZ期间哮喘加重率、伯明翰血管炎活动度评分和皮质类固醇剂量下降(p <0.001, p <0.001和p = 0.001)。5例患者可以停用强的松。MPZ期间感染率较高(p <10-6),但没有观察到住院、哮喘加重或损伤增加。实际数据证实了MPZ治疗难治性EGPA伴活动性哮喘的有效性。较高的感染率与其他研究一致,可能是由于就诊频率增加导致的相对多报,尽管不能排除药理学作用。
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引用次数: 2
Continuous increase of immunoglobulin therapy in Iceland 冰岛免疫球蛋白治疗持续增加
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.06.001
Valgeir Steinn Runólfsson , Björn Rúnar Lúdvíksson , Rannveig Einarsdóttir , Þórunn Óskarsdóttir , Valtýr Thors , Ásgeir Haraldsson

Background

The use of immunoglobulin treatment has been increasing for various indications. The objective of this study was to evaluate clinical use of immunoglobulin therapy in Iceland, estimate off-label usage and describe possible changes in this treatment option.

Methods

All prescriptions for intravenous or subcutaneous immunoglobulin treatment require authorisation from Landspitali University Hospital. Patient information is registered and was retrieved for the period 2010 to 2019.

Results

A total of 921 patients received immunoglobulin treatment in the study period, intravenous therapy was given in 895 (97.2%) of the cases. Registered indications were 667, off-label indications were 245 and uncertain were nine. The total annual number of patients receiving immunoglobulin treatment increased from 87 in 2010 to 392 in 2019. The increase in immunoglobulin usage was both for registered and off-label indications, 61 to 309 and 26 to 83, respectively.

Conclusion

Continually increasing demand and global shortage dictates careful consideration of indications before initiating or continuing treatment with immunoglobulins.

Key Message

With global shortage of immunoglobulins, careful consideration and patient selection is important.

Capsule Summary

Increasing immunoglobulin usage improves treatment for many patients. However, immunoglobulins are a limited resource and prudent use is imperative.

背景免疫球蛋白治疗在各种适应症中的应用越来越多。本研究的目的是评估冰岛免疫球蛋白治疗的临床使用,估计标签外使用情况,并描述这种治疗方案可能发生的变化。方法所有静脉注射或皮下注射免疫球蛋白的处方均需获得兰德斯皮塔利大学医院的批准。注册并检索了2010年至2019年期间的患者信息。结果研究期间共921例患者接受免疫球蛋白治疗,其中895例(97.2%)患者接受静脉注射治疗。注册适应症667例,说明书外适应症245例,不确定适应症9例。每年接受免疫球蛋白治疗的患者总数从2010年的87人增加到2019年的392人。免疫球蛋白的使用在注册适应症和说明书外适应症中均有所增加,分别为61至309例和26至83例。结论持续增长的需求和全球短缺要求在开始或继续使用免疫球蛋白治疗前仔细考虑适应症。随着全球免疫球蛋白的短缺,仔细考虑和患者选择是重要的。增加免疫球蛋白的使用改善了许多患者的治疗。然而,免疫球蛋白是一种有限的资源,必须谨慎使用。
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引用次数: 0
Daily oral vitamin D3 without concomitant therapy in the management of psoriasis: A case series 每日口服维生素D3不伴随治疗牛皮癣的管理:一个病例系列
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.01.001
Renu Mahtani , Pradeep M.K. Nair

Evidence suggests vitamin D3 resistance with gene polymorphisms related to its metabolism to have a potential role in the patho-prognosis of psoriasis. We report 6 cases of psoriasis treated with daily oral Vitamin D3 (25 hydroxy cholecalciferol) in doses ranging from 30,000 IU to 60,000 IU over a period of 2 to 6 months and then followed by lower daily maintenance dose. The dose of vitamin D3 was adjusted based on the drop in the level of parathyroid hormone as the ionized calcium levels were also periodically monitored to prevent hypercalcemia. Complete control of psoriasis was observed within a span of 2–6 months, which was measured by Psoriasis Area and Severity Index (PASI) and a symptom Visual analog scale. Our observations suggest that supervised, daily oral higher than usual Vitamin D3 can be given safely as an effective therapeutic modality for treating psoriasis.

有证据表明,维生素D3耐药及其代谢相关的基因多态性在银屑病的病理预后中具有潜在作用。我们报告了6例牛皮癣患者每日口服维生素D3(25羟基胆钙化醇)治疗,剂量从30,000 IU到60,000 IU,持续2至6个月,然后降低每日维持剂量。维生素D3的剂量根据甲状旁腺激素水平的下降进行调整,同时还定期监测电离钙水平,以防止高钙血症。通过银屑病面积和严重程度指数(PASI)和症状视觉模拟量表测量银屑病在2-6个月内完全控制。我们的观察表明,在监督下,每日口服高于平常的维生素D3可以作为治疗牛皮癣的有效治疗方式安全给予。
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引用次数: 0
Her2 expression can predict the survival of patients with salivary duct carcinoma Her2表达可预测涎腺导管癌患者的生存
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.09.004
Toshiaki Kawano, Takashi Hirano, Sonoka Takakura, Kazue Ito, Masashi Urabe, Kaori Tateyama, Masashi Suzuki

Salivary duct carcinoma (SDC) is a high-grade malignant tumor that mainly develops in the salivary glands, and SDC patients have a 5-year survival rate of less than 50%. Thirteen SDC patients (11 male and 2 female, average age 67.2 years) with primary salivary gland carcinoma who received primary treatment in our department from 2005 to 2016.

Although markers such as androgen receptors and gross cystic disease fluid protein-15 are effective in diagnosing SDC, there are no effective tumor-specific markers for prognosis prediction. Therefore, we investigated the expressions of human epidermal growth factor receptor 2 (Her2), Ki-67, EGFR, p16, P53 and PD-L1, and examined their prognostic effect.

Multivariate analysis showed that high Her2 expression was an exacerbating prognostic factor. In the future, the use of molecular-targeted drugs and immune checkpoint inhibitors for salivary gland malignancies may become more frequent. Her2 expression could be used as a predictor of prognosis.

涎腺导管癌(Salivary导管癌,SDC)是一种主要发生于唾液腺的高级别恶性肿瘤,患者5年生存率不足50%。2005 - 2016年在我科接受原发性唾液腺癌初级治疗的SDC患者13例,男11例,女2例,平均年龄67.2岁。虽然雄激素受体和总囊性疾病液蛋白-15等标志物对诊断SDC有效,但没有有效的肿瘤特异性标志物用于预测预后。因此,我们研究了人表皮生长因子受体2 (Her2)、Ki-67、EGFR、p16、P53和PD-L1的表达,并研究了它们对预后的影响。多因素分析显示,Her2高表达是加重预后的因素。在未来,使用分子靶向药物和免疫检查点抑制剂治疗唾液腺恶性肿瘤可能会变得更加频繁。Her2表达可作为预测预后的指标。
{"title":"Her2 expression can predict the survival of patients with salivary duct carcinoma","authors":"Toshiaki Kawano,&nbsp;Takashi Hirano,&nbsp;Sonoka Takakura,&nbsp;Kazue Ito,&nbsp;Masashi Urabe,&nbsp;Kaori Tateyama,&nbsp;Masashi Suzuki","doi":"10.1016/j.clicom.2022.09.004","DOIUrl":"10.1016/j.clicom.2022.09.004","url":null,"abstract":"<div><p>Salivary duct carcinoma (SDC) is a high-grade malignant tumor that mainly develops in the salivary glands, and SDC patients have a 5-year survival rate of less than 50%. Thirteen SDC patients (11 male and 2 female, average age 67.2 years) with primary salivary gland carcinoma who received primary treatment in our department from 2005 to 2016.</p><p>Although markers such as androgen receptors and gross cystic disease fluid protein-15 are effective in diagnosing SDC, there are no effective tumor-specific markers for prognosis prediction. Therefore, we investigated the expressions of human epidermal growth factor receptor 2 (Her2), Ki-67, EGFR, p16, P53 and PD-L1, and examined their prognostic effect.</p><p>Multivariate analysis showed that high Her2 expression was an exacerbating prognostic factor. In the future, the use of molecular-targeted drugs and immune checkpoint inhibitors for salivary gland malignancies may become more frequent. Her2 expression could be used as a predictor of prognosis.</p></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772613422000245/pdfft?md5=55a1cecc8e62cd16180601ad19dfd669&pid=1-s2.0-S2772613422000245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78832159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influenza A and influenza B antibody determination in an Austrian cohort 奥地利队列甲型流感和乙型流感抗体测定
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.09.002
Elisabeth Mara, Johannes Gratzer, Tobias Mader, Thomas Pekar

Influenza is an infectious respiratory disease caused by influenza A and B, which is a virus characterized by a high mutation rate with new strains appearing regularly, making regular booster vaccinations necessary.

In this study, we evaluated the immune status of Influenza A and B by using ELISA. A questionnaire was utilized to appraise the immunization anamnesis and the stance on vaccination.

In total, 202 probands participated in this study. 35.6% of the probands were vaccinated, 10.9% indicated a confirmed influenza infection. 88.1% had a positive influenza A titer, whereas a positive influenza B titer was determined in only 38.6%. Additionally, a correlation between vaccination and titer could be observed.

In this study, we were able to show a higher vaccination rate in our cohort than the Austrian average. Additionally, a higher percentage showed a positive influenza A titer compared to influenza B titer.

流感是一种由甲型和乙型流感引起的传染性呼吸道疾病,甲型和乙型流感是一种病毒,其特点是突变率高,经常出现新的毒株,因此需要定期接种加强疫苗。在这项研究中,我们用ELISA法评估了甲型流感和乙型流感的免疫状态。采用问卷调查的方式评价免疫记忆情况和对疫苗接种的态度。共有202名先证者参与本研究。35.6%的先证者接种了疫苗,10.9%确诊为流感感染。88.1%为甲型流感阳性,38.6%为乙型流感阳性。此外,可以观察到疫苗接种与滴度之间的相关性。在这项研究中,我们能够证明我们的队列中的疫苗接种率高于奥地利的平均水平。此外,a型流感抗体阳性的比例高于B型流感抗体阳性的比例。
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引用次数: 0
Early-onset Crohn's disease, IgA nephropathy, and hemophagocytic lymphohistiocytosis in a patient with IL-10 receptor deficiency IL-10受体缺乏患者的早发性克罗恩病、IgA肾病和噬血细胞性淋巴组织细胞增多症
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.09.003
Amer Khojah , Lauren Gunderman , Ameera Bukhari , Madeline Schutt , Valeria Cohran

IL-10 receptor (IL-10R) deficiency is a rare immune dysregulation disorder that is characterized by early-onset and life-threatening inflammatory bowel disease (IBD). Activation of the IL-10R inhibits the release of pro-inflammatory cytokines resulting in decreased inflammation. Herein, we present a case of novel homozygous IL-10RA mutation (c.243T>A; p.Y81*) resulting in early-onset Crohn's disease and failure to thrive who was treated with anakinra (IL-1 blocker). His disease course was complicated with IgA nephropathy while anakinra was held for the treatment of osteomyelitis and improved when anakinra was restarted. A year later, he developed inflammatory brain disease and Hemophagocytic Lymphohistiocytosis (HLH), which was treated with high dose steroid and hematopoietic stem cell transplant (HSCT). This case highlights IgA nephropathy, CNS autoinflammation, and HLH as possible extraintestinal manifestations of IL-10 receptor deficiency, especially in the setting of delayed stem cell transplantation.

IL-10受体(IL-10R)缺乏症是一种罕见的免疫失调疾病,以早发性和危及生命的炎症性肠病(IBD)为特征。IL-10R的激活抑制促炎细胞因子的释放,导致炎症减少。在此,我们提出了一个新的纯合IL-10RA突变(c.243T> a;p.Y81*)导致早发性克罗恩病和使用anakinra (IL-1阻滞剂)治疗的患者无法茁壮成长。在阿那白治疗骨髓炎期间,他的病程合并IgA肾病,重新使用阿那白后病情有所改善。一年后,他患上了炎症性脑疾病和噬血细胞性淋巴组织细胞增多症(HLH),接受了大剂量类固醇和造血干细胞移植(HSCT)治疗。本病例强调IgA肾病、中枢神经系统自身炎症和HLH可能是IL-10受体缺乏的肠外表现,特别是在延迟干细胞移植的情况下。
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引用次数: 0
期刊
Clinical Immunology Communications
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