Clinical Immunology Communications最新文献_第2页

Evaluating the heavy/light chain immunoglobulin biomarker for early relapse detection in multiple myeloma: A comparative study with conventional methods 评估重链/轻链免疫球蛋白生物标志物在多发性骨髓瘤早期复发检测中的作用：与传统方法的比较研究

Clinical Immunology Communications

Pub Date : 2025-10-31 DOI: 10.1016/j.clicom.2025.10.003

Carla Azevedo , Ana Catarina Fonseca , João Pedro Barreto , Ana Marta Pires , Carina Faria , Andreia Pinto , Maria Emília Sousa , Carlos Palmeira , Cristina Prudêncio , Bruno Fernandes , Gabriela Martins , Ricardo Ferraz

Objectives

The objective of this study is to evaluate the use of the immunoglobulin heavy/light chain biomarker in the early detection of biochemical relapse in patients with multiple myeloma under treatment. The immunoglobulin heavy/light chain is a test that measures the heavy chain/light chain pair of each immunoglobulin isotype, allowing for the calculation of the immunoglobulin ratios of IgGκ/IgGλ, IgAκ/IgAλ and IgMκ/IgMλ, which can be used as surrogate markers of monoclonal proliferation processes.

Design & Methods

For the study, 80 samples were selected from 40 patients with multiple myeloma, who showed evidence of biochemical relapse in the past 5 years, corresponding to two samples per patient. Heavy/light chain pairs of the monoclonal isotype were determined in the sample that showed biochemical relapse and in the previous follow-up sample. Results were compared with those from serum immunofixation, serum protein electrophoresis, and free light chains.

Results

Within the samples before biochemical relapse, which had negative serum electrophoresis and immunofixation, 18 % had an abnormal heavy/light chain ratio, 33 % had an abnormal free light chain ratio, and 40 % had at least one of these ratios altered. At the moment of biochemical relapse, i.e., samples with positive immunofixation, 43 % had positive serum protein electrophoresis, 43 % had an abnormal heavy/light chain ratio, 58 % had an abnormal free light chain ratio, and 68 % had at least one abnormal ratio.

Conclusions

The assessment of heavy/light chains and free light chains may have a beneficial impact on the early detection of biochemical relapse in patients with multiple myeloma, particularly in IgA-type MM, potentially eliminating the need for serum electrophoresis.

本研究的目的是评估免疫球蛋白重/轻链生物标志物在治疗中的多发性骨髓瘤患者生化复发早期检测中的应用。免疫球蛋白重/轻链是测量每种免疫球蛋白同型的重链/轻链对的测试，允许计算IgGκ/IgGλ， igakk / igab和IgMκ/IgMλ的免疫球蛋白比率，可作为单克隆增殖过程的替代标记物。设计和方法本研究从40例在过去5年中有生化复发迹象的多发性骨髓瘤患者中选择80例样本，相当于每位患者2例样本。在显示生化复发的样本和之前的随访样本中测定单克隆同型的重/轻链对。结果比较了血清免疫固定、血清蛋白电泳和游离轻链检测结果。结果血清电泳和免疫固定阴性的生化复发前标本中，重/轻链比异常占18%，游离轻链比异常占33%，重/轻链比至少改变其中一项的占40%。生化复发时，即免疫固定阳性标本，43%血清蛋白电泳阳性，43%重/轻链比异常，58%游离轻链比异常，68%至少有一项异常。结论重/轻链和游离轻链的评估可能对早期发现多发性骨髓瘤患者的生化复发有有益的影响，特别是在iga型MM中，可能消除对血清电泳的需要。

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引用次数: 0

Papillon-Lefèvre syndrome presenting with early-onset Psoriasis and Osteomyelitis: A case report 以早发性银屑病和骨髓炎为表现的左侧椎体乳头状体综合征1例报告

Clinical Immunology Communications

Pub Date : 2025-10-28 DOI: 10.1016/j.clicom.2025.10.002

Aisha Mirza , Batoul Basalom , Mohammed H Almatrafi , Ameera Bukhari , Amer Khojah

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by palmoplantar hyperkeratosis, severe periodontitis, and recurrent infections. We present the case of an 8-year-old boy with early-onset psoriasis diagnosed in infancy and managed with Adalimumab. He presented with progressive right knee swelling, and intermittent fever. MRI revealed a Brodie abscess with features of osteomyelitis. Abscess fluid culture was positive for methicillin-resistant Staphylococcus aureus. Whole-exome sequencing identified a homozygous missense variant in the CTSC gene (c.899G>A; p.Gly300Asp), confirming the diagnosis of PLS. Interestingly, his dental panoramic x-ray was normal. This case underscores the importance of genetic testing in patients with early-onset psoriasis and atypical infections. Although almost all reported cases of PLS feature early, severe periodontitis, our patient did not show dental involvement. This highlights that younger patients with PLS may present without this classical feature.

乳突-左旋体综合征（PLS）是一种罕见的常染色体隐性遗传病，由组织蛋白酶C （CTSC）基因突变引起，特征为掌跖角化过度、严重牙周炎和反复感染。我们提出的情况下，一个8岁的男孩早发性牛皮癣诊断在婴儿期和管理阿达木单抗。患者表现为进行性右膝肿胀和间歇性发热。MRI显示布罗迪脓肿伴骨髓炎特征。脓肿液培养耐甲氧西林金黄色葡萄球菌阳性。全外显子组测序发现CTSC基因纯合子错义变异（c.899G> a; p.Gly300Asp），证实了PLS的诊断。有趣的是，他的牙齿全景x线正常。本病例强调了基因检测在早发性牛皮癣和非典型感染患者中的重要性。尽管几乎所有报告的PLS病例都表现为早期严重的牙周炎，但我们的患者并未表现出牙齿受累。这表明年轻的PLS患者可能没有这一典型特征。

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引用次数: 0

Functional thermostable postbiotic derivatives from Lactobacillus rhamnosus LRH9 and their bactericidal efficacy 鼠李糖乳杆菌LRH9的功能性耐热后生物衍生物及其杀菌效果

Clinical Immunology Communications

Pub Date : 2025-10-21 DOI: 10.1016/j.clicom.2025.10.001

Irfanulla Sharieff , Mohammed Swaleh , Puneeth SD , M. N Nagendra Prasad

Probiotics are living microorganisms that, when taken in sufficient quantities, promote health and well-being in the host. In numerous industries, including the food and pharmaceutical sectors, lactic acid bacteria are used to make probiotic and dietary supplements. Probiotics have gained popularity for their ability to fight pathogens, boost immunity, balance gut microbiota, and support bowel health. Lactobacillus rhamnosus LRH9, used in the study is a Gram-positive, non-spore-forming, facultative anaerobic rod, genetically characterized and documented for its robustness under stress conditions. The strain is homofermentative, producing lactic acid as its primary metabolite, and exhibits strong tolerance to acidic and bile environments. The strain was selected for its robust antibacterial activity of the postbiotic production and stable bioactivity. Environmental factors such as pH and temperature influenced efficacy, with enhanced activity under acidic conditions and sustained antimicrobial effects even at temperatures above 100 °C, indicating high thermal stability. GC-MS analysis revealed several metabolites, including N-Methyl-2-pyrrolidone (NMP), hexanedioic acid dioctyl ester, and oxetane derivatives—reported for the first time from this strain. Known compounds such as 5-aminovaleric acid, Pyrrolo[1,2-a]pyrazine-1,4-dione, and diisooctyl phthalate were also identified. These metabolites are believed to contribute to the observed antibacterial properties. The findings highlight the potential of L. rhamnosus LRH9-derived antibacterial activity of the postbiotics for applications requiring heat-resistant, broad-spectrum antimicrobial agents, supporting their future use in food preservation pharmaceutical formulations and cosmetics applications.

益生菌是一种活的微生物，如果摄入足够的量，可以促进宿主的健康和福祉。在许多行业，包括食品和制药行业，乳酸菌被用来制造益生菌和膳食补充剂。益生菌因其对抗病原体、增强免疫力、平衡肠道菌群和支持肠道健康的能力而广受欢迎。研究中使用的鼠李糖乳杆菌LRH9是革兰氏阳性，非孢子形成，兼性厌氧棒，具有遗传特征，并记录了其在应激条件下的稳健性。该菌株是同质发酵的，产生乳酸作为其主要代谢物，并表现出对酸性和胆汁环境的强耐受性。该菌株具有较强的抑菌活性和稳定的生物活性。pH和温度等环境因素会影响药效，在酸性条件下活性增强，即使在100°C以上的温度下也能保持抗菌效果，表明热稳定性高。GC-MS分析显示，该菌株的代谢产物包括n -甲基-2-吡罗烷酮（NMP）、己二酸二辛基酯和氧烷衍生物，为首次报道。已知化合物如5-氨基戊酸、吡咯[1,2-a]吡嗪-1,4-二酮和邻苯二甲酸二异辛酯也被鉴定出来。这些代谢物被认为有助于观察到的抗菌特性。这一发现突出了鼠李糖lrh9衍生的后生制剂在耐热、广谱抗菌剂应用中的潜力，支持了它们在食品保鲜、药物配方和化妆品应用中的未来应用。

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引用次数: 0

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

Clinical Immunology Communications

Pub 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

Reprogramming immunity: Emerging therapeutic frontiers and clinical trial advances of CAR-T cell therapy in autoimmune diseases 免疫重编程：CAR-T细胞治疗自身免疫性疾病的新治疗前沿和临床试验进展

Clinical Immunology Communications

Pub Date : 2025-09-11 DOI: 10.1016/j.clicom.2025.09.003

Arpita Mukherjee

Autoimmune diseases result from a breakdown in immune tolerance, leading to chronic activation of autoreactive lymphocytes. Conventional therapies offer symptomatic relief but rarely achieve durable remission. Chimeric antigen receptor (CAR)-T cell therapy, originally developed for hematologic malignancies, is now being repurposed to selectively deplete pathogenic immune subsets in autoimmunity. This review explores how CAR-T cells may not only eliminate autoreactive B and T cells but also reprogram immune homeostasis toward long-term tolerance. Recent clinical success with CD19-directed CAR-T cells in refractory systemic lupus erythematosus underscores this paradigm shift. Furthermore, next-generation constructs including dual CARs, inhibitory CARs (iCARs), and CAR-Tregs offer innovative strategies to balance cytotoxicity with regulatory control. Key challenges such as antigen escape, off-target effects, and therapeutic accessibility are critically analyzed within current translational and clinical landscapes. This work advocates for a mechanistically guided redefinition of autoimmune therapy through precision-engineered immune reprogramming.

自身免疫性疾病源于免疫耐受的破坏，导致自身反应性淋巴细胞的慢性激活。传统疗法能缓解症状，但很少能持久缓解。嵌合抗原受体(CAR)-T细胞疗法最初用于血液系统恶性肿瘤，现在被重新用于选择性地消耗自身免疫中的致病性免疫亚群。这篇综述探讨了CAR-T细胞不仅可以消除自身反应性B细胞和T细胞，还可以重新编程免疫稳态以实现长期耐受性。最近cd19靶向CAR-T细胞治疗难治性系统性红斑狼疮的临床成功强调了这种范式转变。此外，下一代构建物包括双car、抑制性car （iCARs）和CAR-Tregs，提供了平衡细胞毒性和调节控制的创新策略。关键的挑战，如抗原逃逸，脱靶效应，治疗可及性在当前的翻译和临床景观进行了批判性分析。这项工作提倡通过精确工程免疫重编程对自身免疫治疗进行机械指导的重新定义。

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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

Clinical Immunology Communications

Pub 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

Immunologic profiles and infection patterns in patients with down syndrome: A retrospective review 唐氏综合征患者的免疫特征和感染模式：回顾性回顾

Clinical Immunology Communications

Pub Date : 2025-09-07 DOI: 10.1016/j.clicom.2025.09.001

Travis Satnarine , Valishti Pundit , Alana Xavier de Almeida , Matthew Wyke , Gary Kleiner , Melissa Gans

Individuals with Down syndrome (DS) are known to have increased susceptibility to infections, yet the extent of underlying immune dysfunction remains under-characterized. This retrospective study evaluates immune abnormalities in individuals with DS referred for immunologic assessment. A review of electronic records (2010–2023) identified 17 unique patients (mean age 7.4 years). Recurrent infections included otitis media (29 %), viral URIs (24 %), and bacterial LRIs (24 %), though infection types were often poorly documented. Lab abnormalities were frequent: 15/17 (88 %) had ≥1; 9/17 (53 %) had absolute lymphopenia, and among those tested, 6/10 (60 %) had T-, B-, and/or NK-cell lymphopenia. Low immunoglobulins were seen in 7/14 (50 %). Pneumococcal titers were non‑protective in 9/12 (75 %) after the primary series, with only 50 % protective post‑booster. Interventions included additional pneumococcal vaccines (8/12, 67 %) and immunoglobulin therapy (1/17, 6 %). Findings underscore the high rate of immune abnormalities in individuals with DS and support routine immunologic evaluation and tailored interventions. Though referral bias may overestimate prevalence, results highlight the need for proactive immune monitoring in this population.

唐氏综合症（DS）患者已知对感染的易感性增加，但潜在免疫功能障碍的程度仍不清楚。这项回顾性研究评估了退行性椎体滑移患者的免疫异常。电子记录回顾（2010-2023）确定了17例独特患者（平均年龄7.4岁）。复发性感染包括中耳炎（29%）、病毒性uri（24%）和细菌性LRIs(24%)，但感染类型通常文献记载较少。实验室异常频繁：15/17(88%)≥1；9/17（53%）患者有绝对淋巴细胞减少症，6/10（60%）患者有T细胞、B细胞和/或nk细胞淋巴减少症。7/14（50%）出现低免疫球蛋白。在初次接种后，9/12（75%）的肺炎球菌滴度无保护作用，只有50%在加强后具有保护作用。干预措施包括额外的肺炎球菌疫苗（8/ 12,67 %）和免疫球蛋白治疗（1/ 17,6 %）。研究结果强调了DS患者免疫异常的高发率，并支持常规免疫评估和量身定制的干预措施。虽然转诊偏倚可能高估了患病率，但结果强调了在这一人群中进行主动免疫监测的必要性。

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引用次数: 0

Natural and hybrid immunity: A comparative study of T cell response against SARS-CoV-2 自然免疫和混合免疫：T细胞对SARS-CoV-2反应的比较研究

Clinical Immunology Communications

Pub Date : 2025-07-19 DOI: 10.1016/j.clicom.2025.07.001

Arthur Gomes de Andrade , Fernando Cézar Comberlang , Rephany Fonseca Peixoto , Pedro Henrique de Sousa Palmeira , Francisco Sandro Aureliano , Bárbara Guimarães Csordas , Luiz Henrique Agra Cavalcante-Silva , Tatjana S.L. Keesen

Following SARS-CoV-2 infection, COVID-19 vaccination remains prudent as a form of combined protection. This strategy fosters the development of a hybrid immune response in individuals, surpassing the protective efficacy of natural infection or just vaccination. However, many questions remain unsolved, and more studies are needed to understand this type of immunity. Considering this, this study aimed to compare the T-cell immune profile of unvaccinated and vaccinated patients who had previously recovered from mild COVID-19. In a quiescent state characterized, CD8⁺ T cells derived from individuals who had experienced mild COVID-19 and remained unvaccinated exhibited elevated expression of CD69 and IFN-γ compared to the group that received the vaccination. Conversely, within the CD4⁺ T cell population, greater levels of IFN-γ, TNF-α, CD107a, and perforin are observed in the unvaccinated group compared to those vaccinated. Furthermore, a distinct functional profile emerges in T cells obtained from COVID-19-vaccinated patients who experienced mild COVID-19. Upon exposure to spike antigens, CD4⁺ T cells demonstrate heightened activity and functionality. This is evidenced by the augmented expression of CD137, CD69, and IL-10 compared to similarly affected yet unvaccinated patients. Moreover, the CD8⁺ T cell subset within the vaccinated cohort displays heightened levels of perforin, TNF-α, and IL-10 when juxtaposed with the unvaccinated group. These findings collectively imply the ability of unvaccinated individuals to develop an effector-oriented profile in their immune responses. Conversely, individuals who have encountered mild COVID-19 and subsequently received vaccination can orchestrate a proficient antiviral immune response, coupled with a major immunoregulatory capacity.

在SARS-CoV-2感染后，COVID-19疫苗接种作为一种联合保护形式仍然是谨慎的。这一策略促进了个体混合免疫反应的发展，超过了自然感染或仅仅接种疫苗的保护功效。然而，许多问题仍未解决，需要更多的研究来了解这种类型的免疫。考虑到这一点，本研究旨在比较未接种疫苗和接种疫苗的轻度COVID-19患者的t细胞免疫谱。在静止状态下，来自患有轻度COVID-19且未接种疫苗的个体的CD8+ T细胞与接种疫苗的组相比，CD69和IFN-γ的表达升高。相反，在CD4+ T细胞群中，未接种疫苗组的IFN-γ、TNF-α、CD107a和穿孔素水平高于接种疫苗组。此外，从患有轻度COVID-19的COVID-19疫苗接种患者获得的T细胞中出现了独特的功能谱。暴露于刺突抗原后，CD4+ T细胞表现出更高的活性和功能。与未接种疫苗的受类似影响的患者相比，CD137、CD69和IL-10的表达增强证明了这一点。此外，与未接种组相比，接种组的CD8+ T细胞亚群显示穿孔素、TNF-α和IL-10水平升高。这些发现共同表明，未接种疫苗的个体有能力在其免疫反应中形成效应导向的概况。相反，遇到轻度COVID-19并随后接受疫苗接种的个体可以协调熟练的抗病毒免疫反应，并具有主要的免疫调节能力。

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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

Clinical Immunology Communications

Pub 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。

引用次数: 0

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。

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引用次数: 0