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CASPASE-3 expression and activity in PBMCs associate with SARS-CoV-2 infection and clinical features CASPASE-3在PBMCs中的表达和活性与SARS-CoV-2感染和临床特征相关
Pub Date : 2025-12-01 Epub Date: 2025-09-18 DOI: 10.1016/j.clicom.2025.09.004
Vanessa Mylenna Florêncio de Carvalho , Bárbara de Oliveira Silva , Priscilla Stela Santana de Oliveira , Thacianna Barreto da Costa , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Michelly Cristiny Pereira , Maira Galdino da Rocha Pitta

Background

Although vaccines and treatments exist, new SARS-CoV-2 variants continue to emerge. An imbalance between apoptosis and autophagy may contribute to COVID-19 pathogenesis, leading to tissue damage and inflammation.

Objective

To investigate the role of cell death-related proteins during SARS-CoV-2 infection and their associations with clinical variables.

Methods

A total of 140 samples were analyzed (n = 73 infected, n = 67 uninfected). Gene expression of apoptotic and autophagic markers was evaluated by RT-qPCR in peripheral blood mononuclear cells. Caspase 3/7 activity was assessed using flow cytometry.

Results

Infected patients showed higher expression of CASPASE 3, BID (p < 0.05), and MAP1LC3 (p < 0.01). CASPASE 3 expression was higher in variant omicron, male sex, high viral load, and various clinical symptoms. Caspase 3/7 activity increased in CD4⁺ T and B cells of individuals infected with SARS-CoV-2.

Conclusions

Although our previous results with CASPASE 3 are promising and suggest that it may become a potential therapeutic target, additional studies are needed to confirm these hypotheses and evaluate potential intervention strategies.
尽管已有疫苗和治疗方法,但新的SARS-CoV-2变体仍在不断出现。细胞凋亡和自噬之间的不平衡可能导致新冠肺炎的发病机制,导致组织损伤和炎症。目的探讨细胞死亡相关蛋白在SARS-CoV-2感染中的作用及其与临床变量的关系。方法对140份样本进行分析,其中感染病例73例,未感染病例67例。采用RT-qPCR技术检测外周血单核细胞凋亡和自噬标志物的基因表达。流式细胞术检测Caspase 3/7活性。结果感染患者CASPASE 3、BID (p < 0.05)、MAP1LC3表达升高(p < 0.01)。CASPASE 3在变异组粒、男性、高病毒载量和各种临床症状中表达较高。SARS-CoV-2感染者CD4 + T和B细胞中Caspase 3/7活性升高。尽管我们之前关于CASPASE 3的研究结果是有希望的,并表明它可能成为一个潜在的治疗靶点,但需要进一步的研究来证实这些假设并评估潜在的干预策略。
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引用次数: 0
Profiling the serum cytokine B cell activating factor (BAFF),proliferation inducing ligand (APRIL), and BP180, BP230 antibodies in bullous pemphigoid patients before and after treatment: a prospective case-control study 分析大疱性类天疱疮患者治疗前后血清细胞因子B细胞活化因子(BAFF)、增殖诱导配体(APRIL)和BP180、BP230抗体:一项前瞻性病例对照研究
Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI: 10.1016/j.clicom.2025.09.002
Shadab Seraji , Kamran Balighi , Amir Hooshang Ehsani , Ala Ehsani , Hamidreza Mahmoudi , Maryam Daneshpazhooh , Pedram Noormohammadpour , Saman Al Zahawi , Zeinab Aryanian , Parvaneh Hatami

Background

Bullous pemphigoid is a subepidermal autoimmune blistering disease caused by auto-antibodies directed against specific components of the basement membrane molecules. It has been shown that T cell function and B cell survival depend on B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily. Its contribution to the formation of BP is yet unknown, though.

Aim

To measure the serum level of cytokines B cell activating factor (BAFF) and proliferation inducing ligand (APRIL), as well as BP180 and BP230 antibodies in patients with bullous pemphigoid before and after treatment.

Methods

New patients with a confirmed diagnosis of bullous pemphigoid from a tertiary care hospital were selected. After obtaining written consent, blood samples were taken according to the required standards, and the levels of the above indices were checked before and four months after treatment.

Results

This prospective case-control study recruited 32 patients with newly diagnosed BP and 24 healthy controls. Based on the obtained results, BAFF and APRIL levels were higher in the case group than the control group both before and after the treatment. Specifically, the changes in the BAFF index were statistically significant in both conditions: before treatment compared to controls (P = 0.001) and after treatment compared to controls (P = 0.015). Similarly, significant changes were observed in the APRIL index for the cases when comparing before treatment to controls (P < 0.001). Interestingly, those who have been treated with rituximab experienced a high level of BAFF even after treatment and in comparison with the healthy group but a decline in APRIL, BP180, and BP230.

Conclusions

The results of this study showed a decrease in APRIL, BP180, and BP230 indices in patients with Bullous pemphigoid after treatment in accordance with clinical improvement and remission. This study is one step forward in elaborating the role of BAFF and APRIL in the pathogenesis and monitoring of patients with BP.
大疱性类天疱疮是一种表皮下自身免疫性起泡疾病,由自身抗体直接针对基底膜分子的特定成分引起。研究表明,T细胞功能和B细胞存活依赖于B细胞活化因子(BAFF),它是肿瘤坏死因子超家族的一员。不过,它对BP形成的贡献尚不清楚。目的检测大疱性类天疱疮患者治疗前后血清细胞因子B细胞活化因子(BAFF)、增殖诱导配体(APRIL)及BP180、BP230抗体水平。方法选择三级医院确诊为大疱性类天疱疮的新患者。经书面同意后,按规定标准采血,并于治疗前及治疗后4个月检测上述指标水平。结果本前瞻性病例对照研究纳入32例新诊断的BP患者和24例健康对照。结果显示,治疗前后,病例组BAFF和APRIL水平均高于对照组。具体而言,两种情况下BAFF指数的变化均具有统计学意义:治疗前与对照组相比(P = 0.001),治疗后与对照组相比(P = 0.015)。同样,与对照组相比,治疗前患者的APRIL指数也发生了显著变化(P < 0.001)。有趣的是,与健康组相比,接受利妥昔单抗治疗的患者即使在治疗后也经历了高水平的BAFF,但在APRIL、BP180和BP230方面有所下降。结论大疱性类天疱疮患者经治疗后APRIL、BP180、BP230指数下降,符合临床改善和缓解。本研究进一步阐明了BAFF和APRIL在BP发病机制和监测中的作用。
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引用次数: 0
Paraneoplastic neurologic syndromes in breast cancer: Immunological mechanisms and therapeutic insights 乳腺癌的副肿瘤神经系统综合征:免疫学机制和治疗见解
Pub Date : 2025-12-01 Epub Date: 2025-06-28 DOI: 10.1016/j.clicom.2025.06.003
Carolina Coradi , Beatriz Geovana Leite Vacario , Marina Rayciki Sotomayor , Victor Pereira da Silva , Gabriela Bonetti Bellandi , Luísa Cristina Fortuna da Silva , Carlos Frederico de Almeida , Carolina Panis
Research into paraneoplastic neurologic syndromes (PNS) has advanced significantly. This progress is reflected in the continuous refinement of diagnostic criteria and the introduction of novel antibodies for research purposes. Recently, there have been insights into the involvement of T cells in the pathophysiology of certain PNS, although many aspects of the underlying mechanisms remain to be fully understood. In breast cancer, there is emerging evidence linking drug treatments to the onset of PNS, and associated molecular mechanisms enrolling the immune system have been delineated. Here, we explore the evolving understanding of paraneoplastic neurologic syndrome development in breast cancer patients, emphasizing the immunological molecular pathways involved and the role of cytotoxic chemotherapy and immunotherapy in this context.
副肿瘤神经系统综合征(PNS)的研究取得了显著进展。这一进展反映在诊断标准的不断完善和为研究目的引入新的抗体上。最近,人们对T细胞参与某些PNS的病理生理有了深入的了解,尽管其潜在机制的许多方面仍有待充分了解。在乳腺癌中,有新的证据表明药物治疗与PNS的发病有关,并且已经描述了相关的免疫系统分子机制。在这里,我们探讨了对乳腺癌患者副肿瘤神经系统综合征发展的不断发展的理解,强调了所涉及的免疫分子途径以及细胞毒性化疗和免疫治疗在此背景下的作用。
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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
Pub Date : 2025-06-01 Epub 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。
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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
Pub Date : 2025-06-01 Epub 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 ,&nbsp;Heloisa Isabela Leão ,&nbsp;Ryan Cordeiro Silva ,&nbsp;Nathália Tavares Ferreira ,&nbsp;Amanda Pinheiro de Barros Albuquerque ,&nbsp;André Machado de Siqueira ,&nbsp;Michelly Cristiny Pereira ,&nbsp;Michelle Melgarejo da Rosa ,&nbsp;Moacyr Jesus Barreto de Melo Rêgo ,&nbsp;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":"2025-06-01","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
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
Pub Date : 2025-06-01 Epub 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。
{"title":"Serological responses to SARS-CoV-2 in vaccinated and unvaccinated individuals: A Canadian study","authors":"Andrea Monjo ,&nbsp;Tania Rodríguez-Ramos ,&nbsp;Mark R. Bruder ,&nbsp;Nguyen T.K. Vo ,&nbsp;Mark Oremus ,&nbsp;Kevin J. Stinson ,&nbsp;Brian Dixon ,&nbsp;Marc G Aucoin","doi":"10.1016/j.clicom.2025.02.002","DOIUrl":"10.1016/j.clicom.2025.02.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 39-46"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549428","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
Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes 利妥昔单抗治疗后儿科患者持续低丙种球蛋白血症,患病率和临床结果
Pub Date : 2025-06-01 Epub 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 ,&nbsp;Saskia R. Veldkamp ,&nbsp;Mark C.H. de Groot ,&nbsp;Saskia Haitjema ,&nbsp;Julia Drylewicz ,&nbsp;Jaap Jan Boelens ,&nbsp;Caroline A. Lindemans ,&nbsp;Joris van Montfrans ,&nbsp;Annet van Royen-Kerkhof ,&nbsp;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 &lt;-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 (&gt;6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic &gt;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":"2025-06-01","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
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
Pub Date : 2025-06-01 Epub 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
{"title":"Prevalence and significance of anti-citrullinated cyclic peptide antibodies in relapsing polychondritis","authors":"Damien Sène ,&nbsp;Sophie Hue ,&nbsp;Pascale Ghillani-Dalbin ,&nbsp;Sophie Caillat-Zucman ,&nbsp;Jean-Charles Piette","doi":"10.1016/j.clicom.2025.05.003","DOIUrl":"10.1016/j.clicom.2025.05.003","url":null,"abstract":"","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 79-81"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146774","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
Role of skin antimicrobial peptides in the pathogenesis of psoriasis, atopic dermatitis and hidradenitis suppurative: Highlights on dermcidin 皮肤抗菌肽在银屑病、特应性皮炎和化脓性汗腺炎发病机制中的作用:皮肤抗菌肽研究综述
Pub Date : 2025-06-01 Epub Date: 2024-12-13 DOI: 10.1016/j.clicom.2024.12.001
José E Belizário
Diverse classes of antimicrobial peptides (AMPs) produced by keratinocytes, sebocytes, epithelial cells of apocrine and eccrine sweat glands and innate immune cells are continually released in the skin tissue layers. Together they exert the fine homeostatic control of the host immune cells-skin microbiome interactions, inhibiting bacterial overgrowth and skin barrier disruption. Under a variety of pathological conditions, up or down regulation of AMP expression can contribute to microbial diversity imbalance or dysbiosis, which can initiate or worsen the most common cutaneous diseases. This review updates on the roles of dermcidin, defensins, cathelicidins and S100 proteins as modulators of microbiomes, inflammation and recurrent bacterial infections in psoriasis, atopic dermatitis and hidradenitis suppurativa. The top most significant disease-immune signaling pathways mediated by the cytokines IL-1, TNF-α, IL-17, IL-23 and IL-33 are also reviewed. Current studies suggest that raising and lowering of host cell- and bacterial-derived AMPs may directly affect microbiome and immunity homeostasis at local body sites. Molecular genetics and microbiome studies should help us to investigate the bacterial species and AMPs synergistic or harmful interactions with causal gene variants, harnessing their potential clinical application in the journey of skin disease patients.
由角质形成细胞、皮脂细胞、大汗腺和汗腺上皮细胞以及先天免疫细胞产生的各种抗菌肽(AMPs)在皮肤组织层中不断释放。它们共同发挥宿主免疫细胞-皮肤微生物组相互作用的精细稳态控制,抑制细菌过度生长和皮肤屏障破坏。在多种病理条件下,AMP表达的上调或下调可导致微生物多样性失衡或生态失调,从而引发或加重最常见的皮肤疾病。本文综述了在银屑病、特应性皮炎和化脓性汗腺炎中,杀皮素、防御素、抗菌素和S100蛋白作为微生物组、炎症和复发性细菌感染调节剂的作用。综述了IL-1、TNF-α、IL-17、IL-23和IL-33等细胞因子介导的最重要的疾病免疫信号通路。目前的研究表明,宿主细胞和细菌来源的amp的升高和降低可能直接影响局部身体部位的微生物组和免疫稳态。分子遗传学和微生物组研究将有助于我们调查细菌种类和amp与致病基因变异的增效或有害相互作用,利用它们在皮肤病患者旅程中的潜在临床应用。
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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
Pub Date : 2025-06-01 Epub 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。
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引用次数: 0
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Clinical Immunology Communications
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