Clinical Immunology Communications最新文献

英文中文

The role of the T helper 17 and T regulatory cell ratio in the gut-thyroid axis 辅助性T - 17和T调节细胞比例在肠-甲状腺轴中的作用

Clinical Immunology Communications

Pub Date : 2025-06-18 DOI: 10.1016/j.clicom.2025.06.002

Julia Williams, Anna Gruvstad Melén, Michelle Barrow

Alterations to the gut microbiota (GM) and its metabolites have been associated with Hashimoto’s Thyroiditis (HT) via modulation of T helper 17 (Th17) and T regulatory (Treg) cells. However, in comparison to other autoimmune diseases there is a shortfall in research investigating pathophysiological mechanisms. The aim of this review was to evaluate mechanisms linking the GM to the immune modulation of Th17 and Tregs in the context of HT.

A systematic literature search was undertaken in two tranches: 1) review papers; 2) primary human, animal and in vitro evidence. 80 papers met the inclusion criteria. Primary papers were critically appraised using SIGN50 and ARRIVE guidelines. Narrative analysis of the key mechanistic themes from primary studies was conducted and a network diagram was developed.

Th17 has a pathogenic phenotype but the context by which this conversion occurs is less well understood. Results suggested microbiota induced production of interleukin-6, interleukin-23 and serum amyloid A proteins play a role. However, downregulation of Tregs could be a prerequisite given their role in T effector cell suppression. Short-chain fatty acids may promote Treg activity; therefore, reduced levels could create a pathogenic environment. Translocation of lipopolysaccharides was indicated as a potential inducer of Th17. Evidence to support the migration of T cells primed in the intestines to other tissues also provided plausibility for mechanisms involving the gut-thyroid axis.

The findings suggest that the GM and its metabolites have immunomodulatory effects on the Th17/Treg ratio. However, research is lacking in HT patients and experimental thyroiditis animal models.

肠道微生物群（GM）及其代谢物的改变与桥本甲状腺炎（HT）有关，这是通过调节辅助性T 17 （Th17）和T调节（Treg）细胞实现的。然而，与其他自身免疫性疾病相比，对其病理生理机制的研究还存在不足。本综述的目的是评估在HT背景下GM与Th17和Tregs免疫调节的机制。系统的文献检索分为两部分：1)综述论文；2)主要的人类、动物和体外证据。80篇论文符合纳入标准。使用SIGN50和ARRIVE指南对主要论文进行批判性评价。对主要研究中的关键机制主题进行了叙述性分析，并绘制了网络图。Th17具有致病表型，但这种转化发生的背景尚不清楚。结果提示微生物群诱导白介素-6、白介素-23和血清淀粉样蛋白A的产生起一定作用。然而，考虑到Tregs在T效应细胞抑制中的作用，下调Tregs可能是一个先决条件。短链脂肪酸可促进Treg活性；因此，水平降低可能会造成致病性环境。脂多糖易位被认为是Th17的潜在诱导剂。支持T细胞在肠道中迁移到其他组织的证据也为涉及肠-甲状腺轴的机制提供了合理性。结果提示，转基因及其代谢物对Th17/Treg比值具有免疫调节作用。然而，对HT患者和实验性甲状腺炎动物模型的研究缺乏。

{"title":"The role of the T helper 17 and T regulatory cell ratio in the gut-thyroid axis","authors":"Julia Williams, Anna Gruvstad Melén, Michelle Barrow","doi":"10.1016/j.clicom.2025.06.002","DOIUrl":"10.1016/j.clicom.2025.06.002","url":null,"abstract":"<div><div>Alterations to the gut microbiota (GM) and its metabolites have been associated with Hashimoto’s Thyroiditis (HT) via modulation of T helper 17 (Th17) and T regulatory (Treg) cells. However, in comparison to other autoimmune diseases there is a shortfall in research investigating pathophysiological mechanisms. The aim of this review was to evaluate mechanisms linking the GM to the immune modulation of Th17 and Tregs in the context of HT.</div><div>A systematic literature search was undertaken in two tranches: 1) review papers; 2) primary human, animal and <em>in vitro</em> evidence. 80 papers met the inclusion criteria. Primary papers were critically appraised using SIGN50 and ARRIVE guidelines. Narrative analysis of the key mechanistic themes from primary studies was conducted and a network diagram was developed.</div><div>Th17 has a pathogenic phenotype but the context by which this conversion occurs is less well understood. Results suggested microbiota induced production of interleukin-6, interleukin-23 and serum amyloid A proteins play a role. However, downregulation of Tregs could be a prerequisite given their role in T effector cell suppression. Short-chain fatty acids may promote Treg activity; therefore, reduced levels could create a pathogenic environment. Translocation of lipopolysaccharides was indicated as a potential inducer of Th17. Evidence to support the migration of T cells primed in the intestines to other tissues also provided plausibility for mechanisms involving the gut-thyroid axis.</div><div>The findings suggest that the GM and its metabolites have immunomodulatory effects on the Th17/Treg ratio. However, research is lacking in HT patients and experimental thyroiditis animal models.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 10-25"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DOCK8 deficiency patient presenting with purpura fulminans caused by group A β-hemolytic Streptococcus sepsis DOCK8缺乏患者表现为A组β溶血性链球菌脓毒症引起的暴发性紫癜

Clinical Immunology Communications

Pub Date : 2025-06-04 DOI: 10.1016/j.clicom.2025.06.001

Abduarahman Almutairi , Nouf Althubaiti , Khaled Abuneim , Ghaziaa Alanezi , Abdullah Alamer , Imad A El Hag , Fayhan J Alroqi , Abdulrahman Alrasheed , Waleed Al Maneea

We report a male infant presenting with Purpura fulminans (PF) secondary to sepsis caused by group A β-hemolytic Streptococcus (GAS) associated with hyper-IgE syndrome due to deletion mutation in DOCK8. The patient, previously healthy, presented with clinical symptoms of fever, lethargy, hypotension with blood culture confirming GAS infection. Subsequently, he developed purpuric skin lesions on his extremities which progressed to gangrene necessitating amputation of his fingers and toes. The findings underscore the importance of considering inborn error of immunity, especially DOCK8 deficiency, in cases of infant presenting with acute infectious PF.

我们报告了一名男婴因DOCK8缺失突变引起的a组β-溶血性链球菌（GAS）与高ige综合征相关的脓毒症继发于暴发性紫癜（PF）。患者既往健康，临床表现为发热、嗜睡、低血压，血培养证实GAS感染。随后，他的四肢出现紫癜性皮肤病变，并发展为坏疽，需要截肢手指和脚趾。研究结果强调了在婴儿急性感染性PF病例中考虑先天免疫错误，特别是DOCK8缺陷的重要性。

引用次数: 0

Assessment of CD38brightHLA-DR+ T cells using a rapid flow cytometry-based assay to aid in the diagnosis of hemophagocytic lymphohistiocytosis and immune regulatory disorders in adult subjects 使用快速流式细胞术检测CD38brightHLA-DR+ T细胞，以帮助诊断成年受试者的噬血细胞淋巴组织细胞增多症和免疫调节障碍

Clinical Immunology Communications

Pub Date : 2025-05-31 DOI: 10.1016/j.clicom.2025.05.004

Aaruni Khanolkar, Erin Weyers, Ramakrishna Sompallae, Matthew D. Krasowski

Rapid and accurate diagnosis of patients suspected of suffering from hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH) is a critical aspect of timely management for such disorders. Soluble IL-2Rα (sIL-2Rα) and plasma ferritin constitute the mainstay of frontline laboratory investigations performed to establish a clinical diagnosis for these patients. However, there is a paucity of clinical laboratories that perform the sIL-2Rα measurement as a stat test which can delay the diagnosis and management of these patients. Consequently, rapid flow cytometry-based tests that measure T cell activation are currently being evaluated. Previous studies have examined the utility of flow-cytometry based testing in pediatric subjects with HLH and immune dysregulation disorders. In this report, we assessed the utility of our flow-cytometry based test in adult patients suspected of HLH and discuss its performance in relation to what has been reported previously in the literature for pediatric patients.

快速准确地诊断疑似患有高炎性疾病的患者，如噬血细胞性淋巴组织细胞增多症（HLH），是及时治疗此类疾病的关键方面。可溶性IL-2Rα (sIL-2Rα)和血浆铁蛋白是一线实验室调查的主要内容，用于建立这些患者的临床诊断。然而，缺乏临床实验室将sIL-2Rα测量作为一种初始测试，这可能会延迟这些患者的诊断和管理。因此，目前正在评估基于快速流式细胞术的检测T细胞活化的方法。先前的研究已经检查了基于流式细胞术的检测在儿童HLH和免疫失调疾病中的效用。在本报告中，我们评估了我们的基于流式细胞术的检测在疑似HLH的成人患者中的效用，并讨论了其与先前文献中报道的儿科患者的表现的关系。

{"title":"Assessment of CD38brightHLA-DR+ T cells using a rapid flow cytometry-based assay to aid in the diagnosis of hemophagocytic lymphohistiocytosis and immune regulatory disorders in adult subjects","authors":"Aaruni Khanolkar, Erin Weyers, Ramakrishna Sompallae, Matthew D. Krasowski","doi":"10.1016/j.clicom.2025.05.004","DOIUrl":"10.1016/j.clicom.2025.05.004","url":null,"abstract":"<div><div>Rapid and accurate diagnosis of patients suspected of suffering from hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH) is a critical aspect of timely management for such disorders. Soluble IL-2Rα (sIL-2Rα) and plasma ferritin constitute the mainstay of frontline laboratory investigations performed to establish a clinical diagnosis for these patients. However, there is a paucity of clinical laboratories that perform the sIL-2Rα measurement as a <em>stat</em> test which can delay the diagnosis and management of these patients. Consequently, rapid flow cytometry-based tests that measure T cell activation are currently being evaluated. Previous studies have examined the utility of flow-cytometry based testing in pediatric subjects with HLH and immune dysregulation disorders. In this report, we assessed the utility of our flow-cytometry based test in adult patients suspected of HLH and discuss its performance in relation to what has been reported previously in the literature for pediatric patients.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 1-5"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence and significance of anti-citrullinated cyclic peptide antibodies in relapsing polychondritis 抗瓜氨酸环肽抗体在复发性多软骨炎中的流行及意义

Clinical Immunology Communications

Pub Date : 2025-05-23 DOI: 10.1016/j.clicom.2025.05.003

Damien Sène , Sophie Hue , Pascale Ghillani-Dalbin , Sophie Caillat-Zucman , Jean-Charles Piette

引用次数: 0

Gal-9: A potential game-changer in COVID-19 severity assessment 目标9:COVID-19严重程度评估的潜在改变者

Clinical Immunology Communications

Pub Date : 2025-05-13 DOI: 10.1016/j.clicom.2025.05.002

Eduardo Davi Lima da Silva , Heloisa Isabela Leão , Ryan Cordeiro Silva , Nathália Tavares Ferreira , Amanda Pinheiro de Barros Albuquerque , André Machado de Siqueira , Michelly Cristiny Pereira , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Maira Galdino da Rocha Pitta

Background

This study investigates Galectin-9 (Gal-9) as a potential biomarker for COVID-19 severity, aiming to improve patient stratification and guide clinical management.

Design and methods

We analyzed Gal-9 levels (blood and saliva) in 112 mild, 57 severe COVID-19 patients, 93 symptomatic non-COVID-19 individuals, and 70 controls (healthy controls) using ELISA and RT-qPCR.

Results

Both mild and severe COVID-19 patients exhibited elevated Galectin-9 (Gal-9) levels, with severe cases showing significantly higher serum levels (mRNA and protein) compared to mild or healthy controls. This suggests Galectin-9 involvement in the acute phase, as levels declined within 15 days post-diagnosis. Fever and cough correlated with disease severity. ROC analysis demonstrated high accuracy in patient stratification. Furthermore, we detected elevated Galectin-9 protein in the saliva of individuals with mild COVID-19, highlighting its potential as a non-invasive biomarker for early disease detection.

Conclusion

This study identifies Gal-9 as a promising biomarker for COVID-19 severity. Elevated Gal-9 levels hold potential for improved patient stratification and clinical management, highlighting the importance of biomarker research in understanding COVID-19 pathophysiology.

本研究旨在探讨半乳糖凝集素-9 （Galectin-9, Gal-9）作为COVID-19严重程度的潜在生物标志物，以改善患者分层和指导临床管理。设计与方法采用ELISA和RT-qPCR方法分析112例轻、57例重度COVID-19患者、93例有症状的非COVID-19个体和70例对照组（健康对照组）血液和唾液中Gal-9的水平。结果轻、重度COVID-19患者血清Galectin-9 （Gal-9）水平均升高，重症患者血清Galectin-9 （mRNA和蛋白）水平明显高于轻、重度对照组。这表明半乳糖凝集素-9参与急性期，在诊断后15天内水平下降。发烧和咳嗽与疾病严重程度相关。ROC分析显示患者分层具有较高的准确性。此外，我们在轻度COVID-19患者的唾液中检测到半乳糖凝集素-9蛋白升高，这突出了其作为早期疾病检测的非侵入性生物标志物的潜力。本研究确定Gal-9是一种有前景的COVID-19严重程度生物标志物。升高的Gal-9水平具有改善患者分层和临床管理的潜力，突出了生物标志物研究对了解COVID-19病理生理学的重要性。

{"title":"Gal-9: A potential game-changer in COVID-19 severity assessment","authors":"Eduardo Davi Lima da Silva , Heloisa Isabela Leão , Ryan Cordeiro Silva , Nathália Tavares Ferreira , Amanda Pinheiro de Barros Albuquerque , André Machado de Siqueira , Michelly Cristiny Pereira , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Maira Galdino da Rocha Pitta","doi":"10.1016/j.clicom.2025.05.002","DOIUrl":"10.1016/j.clicom.2025.05.002","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates Galectin-9 (Gal-9) as a potential biomarker for COVID-19 severity, aiming to improve patient stratification and guide clinical management.</div></div><div><h3>Design and methods</h3><div>We analyzed Gal-9 levels (blood and saliva) in 112 mild, 57 severe COVID-19 patients, 93 symptomatic non-COVID-19 individuals, and 70 controls (healthy controls) using ELISA and RT-qPCR.</div></div><div><h3>Results</h3><div>Both mild and severe COVID-19 patients exhibited elevated Galectin-9 (Gal-9) levels, with severe cases showing significantly higher serum levels (mRNA and protein) compared to mild or healthy controls. This suggests Galectin-9 involvement in the acute phase, as levels declined within 15 days post-diagnosis. Fever and cough correlated with disease severity. ROC analysis demonstrated high accuracy in patient stratification. Furthermore, we detected elevated Galectin-9 protein in the saliva of individuals with mild COVID-19, highlighting its potential as a non-invasive biomarker for early disease detection.</div></div><div><h3>Conclusion</h3><div>This study identifies Gal-9 as a promising biomarker for COVID-19 severity. Elevated Gal-9 levels hold potential for improved patient stratification and clinical management, highlighting the importance of biomarker research in understanding COVID-19 pathophysiology.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 64-71"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficiency of the interleukin-1 receptor antagonist: Characterizing the molecular consequences of loss-of-function IL1RN variants from structural and biochemical evidence 白细胞介素-1受体拮抗剂的缺乏：从结构和生化证据表征功能丧失的IL1RN变异的分子后果

Clinical Immunology Communications

Pub Date : 2025-05-13 DOI: 10.1016/j.clicom.2025.05.001

Joshua Pillai , Spencer Fang

Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare autoinflammatory disease with neonatal onset defined by periostitis, pustulosis, and sterile osteomyelitis. DIRA is caused by biallelic loss-of-function mutations in the IL1RN gene, including 16 cytogenetic abnormalities to date. Due to the rarity of the condition, limited studies have evaluated the molecular basis and consequences of pathogenic IL1RN variants. Herein, we reviewed structural data from the crystal structure of IL-1Ra/IL-1R1 complex along with complementary experimental evidence from prior studies to characterize impacts on protein folding and binding affinity to IL-1R1. Furthermore, we define the hypomorphic R26X variant and suggest that genomic distance influences the ability of translation reinitiation in the context of DIRA, as another variant in the N-terminal did not undergo the same mechanism. Lastly, we provide a multiple-sequence alignment and structural template to better streamline analyses and reporting of novel IL1RN variants in the near future.

白细胞介素-1受体拮抗剂缺乏症（DIRA）是一种罕见的自身炎症性疾病，新生儿发病为骨膜炎、脓疱病和无菌性骨髓炎。DIRA是由IL1RN基因的双等位基因功能丧失突变引起的，迄今为止包括16种细胞遗传学异常。由于这种疾病的罕见性，有限的研究评估了致病性IL1RN变异的分子基础和后果。在此，我们回顾了IL-1Ra/IL-1R1复合体的晶体结构数据以及先前研究的补充实验证据，以表征对蛋白质折叠和与IL-1R1结合亲和力的影响。此外，我们定义了亚形态R26X变体，并提出基因组距离影响DIRA背景下翻译重新启动的能力，因为n端的另一个变体没有经历相同的机制。最后，我们提供了一个多序列比对和结构模板，以便在不久的将来更好地简化分析和报告新的IL1RN变异。

{"title":"Deficiency of the interleukin-1 receptor antagonist: Characterizing the molecular consequences of loss-of-function IL1RN variants from structural and biochemical evidence","authors":"Joshua Pillai , Spencer Fang","doi":"10.1016/j.clicom.2025.05.001","DOIUrl":"10.1016/j.clicom.2025.05.001","url":null,"abstract":"<div><div>Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare autoinflammatory disease with neonatal onset defined by periostitis, pustulosis, and sterile osteomyelitis. DIRA is caused by biallelic loss-of-function mutations in the <em>IL1RN</em> gene, including 16 cytogenetic abnormalities to date. Due to the rarity of the condition, limited studies have evaluated the molecular basis and consequences of pathogenic <em>IL1RN</em> variants. Herein, we reviewed structural data from the crystal structure of IL-1Ra/IL-1R1 complex along with complementary experimental evidence from prior studies to characterize impacts on protein folding and binding affinity to IL-1R1. Furthermore, we define the hypomorphic R26X variant and suggest that genomic distance influences the ability of translation reinitiation in the context of DIRA, as another variant in the N-terminal did not undergo the same mechanism. Lastly, we provide a multiple-sequence alignment and structural template to better streamline analyses and reporting of novel <em>IL1RN</em> variants in the near future.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 72-78"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes

Clinical Immunology Communications

Pub Date : 2025-04-29 DOI: 10.1016/j.clicom.2025.04.001

Susanna P.C. Höppener , Saskia R. Veldkamp , Mark C.H. de Groot , Saskia Haitjema , Julia Drylewicz , Jaap Jan Boelens , Caroline A. Lindemans , Joris van Montfrans , Annet van Royen-Kerkhof , Marc H.A. Jansen

Hypogammaglobulinemia is a known side effect of rituximab (RTX) in adults, but its prevalence and persistence in children remain underexplored. This retrospective cohort study at a tertiary care center examines the prevalence and clinical outcomes of hypogammaglobulinemia in pediatric patients after RTX therapy. Patients aged ≤ 18 years treated with RTX for various indications between 2000 and 2020 were included. Patients were classified as having hypogammaglobulinemia when (1) IgG levels were <-2SD below reference for age, or (2) when they received immunoglobulin replacement therapy (IGRT) for the indication hypogammaglobulinemia. Hypogammaglobulinemia after RTX treatment was observed in 74/134 patients (55.2 %). Persistent hypogammaglobulinemia (>6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic >5 years. Low baseline IgG and IgM levels were significantly associated with persistent hypogammaglobulinemia, while patients receiving RTX therapy for autoimmune diseases were less frequently affected. CD19⁺ B cells reconstituted in a median of 11 months (IQR=[7.3–18.0]), while CD19⁺CD27⁺IgG⁺ switched memory B cells took significantly longer, with a median of 1.8 years (IQR=[1.0–2.9]). Three patients developed class-switch recombination-deficiencies and never recovered. Recurrent infections, of which two fatal, were recorded in 18 patients and were significantly more prevalent in those with persistent hypogammaglobulinemia. In conclusion, over half of children had low IgG levels and/or required IGRT for hypogammaglobulinemia following RTX therapy. Persistent hypogammaglobulinemia was associated with low pre-RTX IgG and/or IgM levels. Children with hypogammaglobulinemia after RTX are often IGRT-dependent, experience recurrent (and sometimes fatal) infections, and may develop secondary immunoglobulin class-switch defects.

低γ -球蛋白血症是已知的成人利妥昔单抗（RTX）的副作用，但其在儿童中的患病率和持久性仍未得到充分研究。这项在三级保健中心进行的回顾性队列研究调查了RTX治疗后儿科患者低丙种球蛋白血症的患病率和临床结果。纳入了2000年至2020年期间接受RTX治疗的各种适应症的年龄≤18岁的患者。当(1)IgG水平低于年龄参考值-2SD，或(2)接受免疫球蛋白替代疗法（IGRT）治疗低γ球蛋白血症时，患者被归类为低γ球蛋白血症。134例患者中有74例（55.2%）在RTX治疗后出现低γ -球蛋白血症。91例患者中有46例（50.5%）出现持续性低γ -球蛋白血症（6个月），其中9例患者维持低γ -球蛋白血症5年。低基线IgG和IgM水平与持续性低丙种球蛋白血症显著相关，而接受RTX治疗自身免疫性疾病的患者较少受到影响。CD19+ B细胞的重构中位数为11个月（IQR=[7.3-18.0]），而CD19+CD27+IgG+开关记忆B细胞的重构中位数为1.8年（IQR=[1.0-2.9]）。三名患者出现了类转换重组缺陷，并且从未康复。在18例患者中记录了复发性感染，其中2例死亡，并且在持续性低丙种球蛋白血症患者中更为普遍。总之，超过一半的儿童在RTX治疗后IgG水平低和/或需要IGRT治疗低丙种球蛋白血症。持续性低丙种球蛋白血症与rtx前IgG和/或IgM水平低有关。RTX后低γ球蛋白血症的儿童通常是igrt依赖性的，经历复发性（有时是致命的）感染，并可能发生继发性免疫球蛋白类转换缺陷。

{"title":"Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes","authors":"Susanna P.C. Höppener , Saskia R. Veldkamp , Mark C.H. de Groot , Saskia Haitjema , Julia Drylewicz , Jaap Jan Boelens , Caroline A. Lindemans , Joris van Montfrans , Annet van Royen-Kerkhof , Marc H.A. Jansen","doi":"10.1016/j.clicom.2025.04.001","DOIUrl":"10.1016/j.clicom.2025.04.001","url":null,"abstract":"<div><div>Hypogammaglobulinemia is a known side effect of rituximab (RTX) in adults, but its prevalence and persistence in children remain underexplored. This retrospective cohort study at a tertiary care center examines the prevalence and clinical outcomes of hypogammaglobulinemia in pediatric patients after RTX therapy. Patients aged ≤ 18 years treated with RTX for various indications between 2000 and 2020 were included. Patients were classified as having hypogammaglobulinemia when (1) IgG levels were <-2<em>SD</em> below reference for age, or (2) when they received immunoglobulin replacement therapy (IGRT) for the indication hypogammaglobulinemia. Hypogammaglobulinemia after RTX treatment was observed in 74/134 patients (55.2 %). Persistent hypogammaglobulinemia (>6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic >5 years. Low baseline IgG and IgM levels were significantly associated with persistent hypogammaglobulinemia, while patients receiving RTX therapy for autoimmune diseases were less frequently affected. CD19<sup>+</sup> <em>B</em> cells reconstituted in a median of 11 months (<em>IQR</em>=[7.3–18.0]), while CD19<sup>+</sup>CD27<sup>+</sup>IgG<sup>+</sup> switched memory B cells took significantly longer, with a median of 1.8 years (<em>IQR</em>=[1.0–2.9]). Three patients developed class-switch recombination-deficiencies and never recovered. Recurrent infections, of which two fatal, were recorded in 18 patients and were significantly more prevalent in those with persistent hypogammaglobulinemia. In conclusion, over half of children had low IgG levels and/or required IGRT for hypogammaglobulinemia following RTX therapy. Persistent hypogammaglobulinemia was associated with low pre-RTX IgG and/or IgM levels. Children with hypogammaglobulinemia after RTX are often IGRT-dependent, experience recurrent (and sometimes fatal) infections, and may develop secondary immunoglobulin class-switch defects.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 55-63"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expansion of SARS-CoV-2 mutations in patient with B-cell lymphoma and rare combination of ACE2, TLR4, DDX58 and IFIH1 variations: A retrospective analysis of the virus-host interplay b细胞淋巴瘤患者中SARS-CoV-2突变的扩增和ACE2、TLR4、DDX58和IFIH1变异的罕见组合：病毒-宿主相互作用的回顾性分析

Clinical Immunology Communications

Pub Date : 2025-02-28 DOI: 10.1016/j.clicom.2025.02.001

Angelina Trifonova , Adelina Yosifova , Atanas Syarov , Andrey Velichkov , Martin Pasev , Svetlomir Takov , Kalina Madarzhieva , Krassimir Angelov , Radoslava Vazharova , Velislava Terzieva

Lessons from the COVID-19 outbreak suggest a highly variable individual clinical course of infection and unpredictable outcomes among infected individuals. In this retrospective study, we examined the intra-host viral evolution in an immunocompromised patient with B-cell lymphoma, severe COVID-19, and a two-stage, long-lasting in-hospital period with lethal outcome. The whole-genome sequencing profile demonstrated a dynamic accumulation of new viral mutations in the entire viral genome, mainly in S1-RBD and Nsp12, against the background of antiviral treatment and convalescent plasma transfusion. Long range-PCR and nanopore sequencing of ACE2, TLR7, TLR8, TLR4, DDX58, and IFIH1 genes revealed single nucleotide substitutions in the ACE2, TLR4, DDX58, IFIH1, and TLR7 receptors, negatively affecting the disease course from the onset. Our results demonstrate that genetic variations in host innate immunity and impaired adaptive immunity facilitate the accumulation of viral mutations that overcome antiviral treatment and passive antibody transfer, affecting the course of SARS-CoV-2 infection.

2019冠状病毒病疫情的教训表明，个体感染的临床过程变化很大，感染者的结果不可预测。在这项回顾性研究中，我们研究了一名免疫功能低下的b细胞淋巴瘤患者的宿主内病毒进化，该患者合并了严重的COVID-19，并出现了两期长期住院治疗的致命结果。全基因组测序显示，在抗病毒治疗和恢复期血浆输注的背景下，整个病毒基因组中出现了新的病毒突变的动态积累，主要集中在S1-RBD和Nsp12。ACE2、TLR7、TLR8、TLR4、DDX58和IFIH1基因的远程pcr和纳米孔测序显示，ACE2、TLR4、DDX58、IFIH1和TLR7受体的单核苷酸取代，从发病开始就对病程产生负面影响。我们的研究结果表明，宿主先天免疫和适应性免疫受损的遗传变异促进了病毒突变的积累，这些突变克服了抗病毒治疗和被动抗体转移，影响了SARS-CoV-2感染的过程。

{"title":"Expansion of SARS-CoV-2 mutations in patient with B-cell lymphoma and rare combination of ACE2, TLR4, DDX58 and IFIH1 variations: A retrospective analysis of the virus-host interplay","authors":"Angelina Trifonova , Adelina Yosifova , Atanas Syarov , Andrey Velichkov , Martin Pasev , Svetlomir Takov , Kalina Madarzhieva , Krassimir Angelov , Radoslava Vazharova , Velislava Terzieva","doi":"10.1016/j.clicom.2025.02.001","DOIUrl":"10.1016/j.clicom.2025.02.001","url":null,"abstract":"<div><div>Lessons from the COVID-19 outbreak suggest a highly variable individual clinical course of infection and unpredictable outcomes among infected individuals. In this retrospective study, we examined the intra-host viral evolution in an immunocompromised patient with B-cell lymphoma, severe COVID-19, and a two-stage, long-lasting in-hospital period with lethal outcome. The whole-genome sequencing profile demonstrated a dynamic accumulation of new viral mutations in the entire viral genome, mainly in S1-RBD and Nsp12, against the background of antiviral treatment and convalescent plasma transfusion. Long range-PCR and nanopore sequencing of <em>ACE2, TLR7, TLR8, TLR4, DDX58,</em> and <em>IFIH1</em> genes revealed single nucleotide substitutions in the ACE2, TLR4, DDX58, IFIH1, and TLR7 receptors, negatively affecting the disease course from the onset. Our results demonstrate that genetic variations in host innate immunity and impaired adaptive immunity facilitate the accumulation of viral mutations that overcome antiviral treatment and passive antibody transfer, affecting the course of SARS-CoV-2 infection.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 47-54"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577284","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

Serological responses to SARS-CoV-2 in vaccinated and unvaccinated individuals: A Canadian study 接种疫苗和未接种疫苗的个体对SARS-CoV-2的血清学反应：一项加拿大研究

Clinical Immunology Communications

Pub Date : 2025-02-28 DOI: 10.1016/j.clicom.2025.02.002

Andrea Monjo , Tania Rodríguez-Ramos , Mark R. Bruder , Nguyen T.K. Vo , Mark Oremus , Kevin J. Stinson , Brian Dixon , Marc G Aucoin

COVID-19 severity has been correlated with older age, male sex, and the presence of comorbidities; it is hypothesized that SARS-CoV-2 antibody responses are also correlated.159 unvaccinated patients with SARS-CoV-2 infections were assessed for IgA, IgG, and IgM titers, which were compared with disease severity, age, sex, presence of comorbidities, and time since infection. Anti-S and anti-Nucleocapsid (N) IgG responses were compared between unvaccinated and vaccinated SARS-CoV-2 positive patients. Anti-S IgA and IgM were better indicators of disease severity than IgG. IgG responses were more likely for patients over 60 years old. Female patients over 60 were more likely to have an antibody response than female patients under 60. Vaccinated patients had a stronger IgG response against S protein than against N protein likely due to immune imprinting. Disease severity was correlated with anti-S antibody responses and comorbidities in unvaccinated patients.

COVID-19严重程度与年龄较大、男性和是否存在合并症相关；假设SARS-CoV-2抗体反应也相关。对159例未接种疫苗的SARS-CoV-2感染患者进行了IgA、IgG和IgM滴度评估，并与疾病严重程度、年龄、性别、是否存在合并症和感染时间进行了比较。比较未接种疫苗和接种疫苗的SARS-CoV-2阳性患者的抗s和抗核衣壳(N) IgG反应。与IgG相比，抗s IgA和IgM是更好的疾病严重程度指标。60岁以上的患者更有可能出现IgG反应。60岁以上的女性患者比60岁以下的女性患者更容易产生抗体反应。接种疫苗的患者对S蛋白的IgG反应强于对N蛋白的IgG反应，这可能是由于免疫印迹所致。在未接种疫苗的患者中，疾病严重程度与抗s抗体反应和合并症相关。

引用次数: 0

Fever of unknown origin in a dialysis patient: A case report of dialyzer membrane allergy 透析患者不明原因发热：透析膜过敏1例报告

Clinical Immunology Communications

Pub Date : 2025-01-09 DOI: 10.1016/j.clicom.2025.01.001

Muhammad Adnan Zaman , Tahlyn Miller , Warsha Korani , Mina Jilani

Fever following hemodialysis presents a diagnostic challenge, often raising concerns about infection. However, non-infectious causes, such as allergic reactions to dialysis membranes, must also be considered. Dialyzer-related reactions, particularly to synthetic membranes like polysulfone, are increasingly recognized as contributors to post-dialysis fever. Although modern dialysis technology has improved biocompatibility by eliminating acetate buffers and sterilizing ethylene oxide, acute hypersensitivity reactions still occur. These reactions are classified into Type A (anaphylactic) and Type B (non-anaphylactic), each with distinct symptoms. Proper identification of these reactions is essential for management, as switching to a more biocompatible membrane is often required. This case report describes a 38-year-old male who developed a fever after hemodialysis in a prison facility. Initial workup ruled out infection, with negative blood cultures and elevated IgE levels suggesting a hypersensitivity reaction to the polysulfone membrane. The patient's symptoms resolved following a switch to a hypoallergenic dialyzer.

血液透析后发热是一项诊断挑战，常常引起对感染的担忧。然而，非感染性原因，如透析膜过敏反应，也必须考虑。透析相关反应，特别是合成膜，如聚砜，越来越被认为是透析后发烧的原因。虽然现代透析技术通过消除醋酸缓冲液和灭菌环氧乙烷改善了生物相容性，但急性超敏反应仍然发生。这些反应分为A型（过敏性）和B型（非过敏性），每种反应都有不同的症状。正确识别这些反应对于管理至关重要，因为通常需要切换到更生物相容性的膜。本病例报告描述了一名38岁男性在监狱设施进行血液透析后出现发烧。最初的检查排除了感染，血培养阴性和IgE水平升高表明对聚砜膜有过敏反应。改用低过敏性透析器后，患者症状消失。

{"title":"Fever of unknown origin in a dialysis patient: A case report of dialyzer membrane allergy","authors":"Muhammad Adnan Zaman , Tahlyn Miller , Warsha Korani , Mina Jilani","doi":"10.1016/j.clicom.2025.01.001","DOIUrl":"10.1016/j.clicom.2025.01.001","url":null,"abstract":"<div><div>Fever following hemodialysis presents a diagnostic challenge, often raising concerns about infection. However, non-infectious causes, such as allergic reactions to dialysis membranes, must also be considered. Dialyzer-related reactions, particularly to synthetic membranes like polysulfone, are increasingly recognized as contributors to post-dialysis fever. Although modern dialysis technology has improved biocompatibility by eliminating acetate buffers and sterilizing ethylene oxide, acute hypersensitivity reactions still occur. These reactions are classified into Type A (anaphylactic) and Type B (non-anaphylactic), each with distinct symptoms. Proper identification of these reactions is essential for management, as switching to a more biocompatible membrane is often required. This case report describes a 38-year-old male who developed a fever after hemodialysis in a prison facility. Initial workup ruled out infection, with negative blood cultures and elevated IgE levels suggesting a hypersensitivity reaction to the polysulfone membrane. The patient's symptoms resolved following a switch to a hypoallergenic dialyzer.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 34-38"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167299","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

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Clinical Immunology Communications

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀