Clinical immunology最新文献

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Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study. Vamifeport，一种临床阶段口服转运铁蛋白抑制剂，缓解小鼠狼疮性肾炎：一项初步研究。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-03-13 DOI: 10.1016/j.clim.2026.110699

Divya Katikaneni, Tanmay Arekar, Leena Al-Hraki, Gabriella Garcia, Norah Reedy, Laurence Morel, Vania Manolova, Yogesh Scindia

Even after immunosuppression, the rate of complete remission for proliferative lupus nephritis (LN) remains around 50%, highlighting the need for identifying novel therapeutic targets. Iron exacerbates LN, and treatments with hepcidin, the primary regulator of systemic iron metabolism, ameliorates LN. This identifies ferroportin, the only known hepcidin receptor, as a target to alleviate LN. Vamifeport is an oral ferroportin inhibitor with promising results in patients with non-transfusion-dependent beta thalassemia. We demonstrate that oral vamifeport administration attenuates renal pathology in MRL/lpr mice, independently of circulating autoantibodies and glomerular immune complex deposits. We identified that vamifeport reduces ferroportin expression on primary monocytes and attenuates LN serum-induced inflammation in monocyte-derived macrophages (MDM), but not in human renal proximal tubular epithelial cells (ferroportin-expressing cells in the kidney). Collectively, our study suggests that vamifeport has a high potential to be further developed clinically as an adjunct therapeutic to treat LN.

即使在免疫抑制后，增殖性狼疮性肾炎（LN）的完全缓解率仍保持在50%左右，这突出了确定新的治疗靶点的必要性。铁加重了LN，用hepcidin治疗（系统性铁代谢的主要调节剂）可以改善LN。这证实了铁转运蛋白，唯一已知的hepcidin受体，作为减轻LN的靶标。Vamifeport是一种口服铁转运蛋白抑制剂，对非输血依赖性β地中海贫血患者有很好的疗效。我们证明口服vamifeport减轻MRL/lpr小鼠的肾脏病理，独立于循环自身抗体和肾小球免疫复合物沉积。我们发现，vamifeport降低了原代单核细胞中铁转运蛋白的表达，并减轻了单核细胞源性巨噬细胞（MDM）中LN血清诱导的炎症，但在人肾近端小管上皮细胞（肾脏中表达铁转运蛋白的细胞）中没有作用。总的来说，我们的研究表明，vamifeport作为治疗LN的辅助疗法在临床上有很大的发展潜力。

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引用次数: 0

Plasma anti-FDX1 autoantibody as a potential biomarker for detection and diagnosis of breast cancer. 血浆抗fdx1自身抗体作为检测和诊断乳腺癌的潜在生物标志物。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-03-12 DOI: 10.1016/j.clim.2026.110697

Fangfang Liu, Yunhui Qu, Peiqi Yu, Jingjing Liu

Autoantibodies have emerged as highly valuable biomarkers for cancer detection. Ferredoxin 1 (FDX1), a key cuproptosis regulator, significantly influences breast cancer prognosis. This study aimed to investigate whether the anti-FDX1 autoantibody can serve as a novel biomarker for breast cancer detection and diagnosis. Anti-FDX1 levels were detected in plasma from 336 breast cancer patients (BC), 220 patients with benign breast nodule (BBN), and 236 normal controls (NC) using ELISA assay. Anti-FDX1 levels in BC were lower than that in NC and BBN. Subgroup analysis revealed enhanced diagnostic efficacy in Luminal A patients aged <50 years: compared with NC, AUC = 0.746 (95% CI: 0.666-0.825); compared with BBN, AUC = 0.695 (95% CI: 0.611-0.780). The combined model of anti-FDX1 and CEA further improved the diagnostic efficacy. The anti-FDX1 autoantibody had high diagnostic value for breast cancer, and the combined model with CEA further optimized the early screening and diagnosis for breast cancer in young women.

自身抗体已成为癌症检测中非常有价值的生物标志物。铁氧化还原蛋白1 （FDX1）是一种重要的铜增生调节因子，对乳腺癌预后有重要影响。本研究旨在探讨抗fdx1自身抗体是否可以作为乳腺癌检测和诊断的新型生物标志物。采用ELISA法检测336例乳腺癌患者（BC）、220例乳腺良性结节患者（BBN）和236例正常人（NC）血浆中抗fdx1水平。BC组抗fdx1水平低于NC和BBN组。亚组分析显示老年Luminal A患者的诊断效能提高

引用次数: 0

Single-cell RNA sequencing provides insights into the potential cellular origins and microenvironment of Extramammary Paget's disease. 单细胞RNA测序提供了对乳腺外佩吉特病的潜在细胞起源和微环境的见解。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-03-12 DOI: 10.1016/j.clim.2026.110698

Rui Li, Feifei Ren, Hongyang Li, Qi Sun, Meilin Ding, Dongqing Li, Wei Cheng, Hao Chen, Jianfang Sun, Mingjun Jiang, Xinfeng Wu, Liming Huang, Liang Zhao, Yong Yang, Meiling Zheng, Wei Zhang

Extramammary Paget's disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential. The exact origin of the tumor is still undefined. To explore potential cellular origin-related signals and depict a relatively comprehensive cellular landscape of EMPD, we collected 50,180 cells from patients with EMPD. We detected a distinct basal keratinocyte cell population characterized by New York Breast-1 (NY-BR-1) expression, which exhibited a transcriptional trajectory toward Paget-like phenotype. We also presented a comprehensive single-cell profile of immune cells and fibroblasts in EMPD. The fibroblasts exhibited a markedly central position in outgoing and incoming signaling interactions. The upregulation of the MK pathway and the downregulation of the MIF pathway in EMPD may promote fibroblast-immune crosstalk and tumor progression. This study provided a novel perspective on potential origin-related transcriptional programs in EMPD and highlighted a global reprogramming of cell-cell communication in EMPD, driven predominantly by fibroblast-derived interactions.

乳腺外佩吉特病（EMPD）是一种经常复发并具有转移潜力的恶性肿瘤。肿瘤的确切来源尚不清楚。为了探索潜在的细胞起源相关信号并描绘EMPD的相对全面的细胞景观，我们从EMPD患者中收集了50,180个细胞。我们检测到以New York Breast-1 （NY-BR-1）表达为特征的基底角化细胞群，其表现出向paget样表型的转录轨迹。我们还介绍了EMPD中免疫细胞和成纤维细胞的综合单细胞谱。成纤维细胞在输出和输入信号相互作用中表现出明显的中心位置。EMPD中MK通路的上调和MIF通路的下调可能促进成纤维细胞免疫串扰和肿瘤进展。这项研究为EMPD中潜在的与起源相关的转录程序提供了一个新的视角，并强调了EMPD中细胞-细胞通信的全局重编程，主要由成纤维细胞衍生的相互作用驱动。

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引用次数: 0

Single-cell dissection of CD8+ T cell-driven immune dysregulation in type 1 diabetes mellitus: Mechanistic links to diabetic foot pathogenesis 1型糖尿病CD8+ T细胞驱动的免疫失调的单细胞解剖：与糖尿病足发病机制的联系

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-11-25 DOI: 10.1016/j.clim.2025.110646

Pengbo Yang , Huhe Bao , Guanwen Sun , Yaxing Zhang

Background

Type 1 diabetes (T1DM) is characterized by autoimmune destruction of pancreatic β-cells and systemic immune dysregulation, yet the cellular networks driving disease progression and their potential link to diabetic complications remain unclear.

Methods

We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from 46 stage 3 T1DM patients and 31 matched controls, integrating transcriptomic, cellular interaction, and functional enrichment analyses.

Results

Unsupervised clustering of 87,542 cells revealed profound immune dysregulation in T1DM, including cytotoxic CD8+ T cell expansion (70 % increase) and Treg depletion (>50 % reduction). CD8+ T cells exhibited hyperactivation of cytotoxic effectors (GNLY, GZMB) and inflammatory mediators (IL32, S100A4), alongside suppressed regulatory genes (FOXP3, IL2RA). Cell-cell communication analysis identified amplified GALECTIN-CD44 signaling between monocytes/DCs and CD8+ T/NK cells, driving proinflammatory crosstalk. Strikingly, a novel exhausted CD4+ subset (PDCD1+, LAG3+) emerged exclusively in T1DM.

Conclusion

Our findings establish CD8+ T cells as central orchestrators of T1DM pathogenesis through synergistic cytotoxic hyperactivity and regulatory collapse. The identified GALECTIN-CD44 axis and JAK-STAT/TGF-β imbalances may extend beyond pancreatic autoimmunity, providing mechanistic insights into systemic complications (e.g., impaired wound healing and chronic inflammation) observed in diabetic patients. These dysregulated networks offer novel therapeutic targets for restoring immune homeostasis in T1DM and its associated comorbidities.

1型糖尿病（T1DM）的特征是胰腺β细胞的自身免疫破坏和全身免疫失调，然而驱动疾病进展的细胞网络及其与糖尿病并发症的潜在联系尚不清楚。方法对46例3期T1DM患者和31例匹配对照的外周血单个核细胞（PBMCs）进行单细胞RNA测序（scRNA-seq），整合转录组学、细胞相互作用和功能富集分析。结果87,542个细胞的监督聚类显示T1DM中存在严重的免疫失调，包括细胞毒性CD8+ T细胞扩增（增加70%）和Treg消耗（减少50%）。CD8+ T细胞表现出细胞毒性效应物（GNLY， GZMB）和炎症介质（IL32, S100A4）的过度激活，以及抑制的调节基因（FOXP3, IL2RA）。细胞-细胞通讯分析发现，单核细胞/ dc和CD8+ T/NK细胞之间的GALECTIN-CD44信号扩增，驱动促炎串扰。引人注目的是，一种新的耗尽CD4+亚群（PDCD1+, LAG3+）仅在T1DM中出现。结论CD8+ T细胞通过协同细胞毒性亢进和调节性崩溃在T1DM发病机制中起着中心协调作用。已确定的GALECTIN-CD44轴和JAK-STAT/TGF-β失衡可能超出胰腺自身免疫的范围，为糖尿病患者观察到的全身并发症（例如伤口愈合受损和慢性炎症）提供了机制见解。这些失调的网络为恢复T1DM及其相关合并症的免疫稳态提供了新的治疗靶点。

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引用次数: 0

The dual role of the COX-2/PGE2 Axis in multiple sclerosis: From pathogenesis to pharmacological inhibition COX-2/PGE2轴在多发性硬化中的双重作用：从发病机制到药理抑制

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-11-22 DOI: 10.1016/j.clim.2025.110643

Ahmed Salem Al-Dhahi , Hayder M. Al-kuraishy , Nawar R. Hussain , Mohamed N. Fawzy , Mubarak Alruwaili , Huda J. Waheed , Ali I. Al-Gareeb , Ali K. Albuhadily , Gaber El-Saber Batiha

Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease of the central nervous system (CNS). The cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) axis plays a complex, dual role in its pathogenesis. Although its upregulation typically induces neuroinflammation, oligodendrocyte apoptosis, and demyelination, certain PGE2 receptors (EP2/EP4) can also mediate protective effects. In experimental models, inhibiting COX-2 (using celecoxib or meloxicam) or blocking pro-inflammatory receptors (EP1/EP3) alleviates disease pathology by reducing immune cell infiltration and cytokine production and protecting oligodendrocytes via both COX-2-dependent and independent mechanisms. This review discusses the potential of selectively targeting the detrimental effects of the COX-2/PGE2 axis (such as EP1/EP3 signaling) while preserving protective pathways as a sophisticated therapeutic strategy for MS. However, cardiovascular risks limit the clinical translation of COX-2 inhibitors, necessitating the development of safer, more precise modulation of this pathway.

多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性神经炎症和脱髓鞘疾病。环氧合酶-2/前列腺素E2 （COX-2/PGE2）轴在其发病机制中起着复杂的双重作用。虽然其上调通常会引起神经炎症、少突胶质细胞凋亡和脱髓鞘，但某些PGE2受体（EP2/EP4）也可以介导保护作用。在实验模型中，抑制COX-2（使用塞来昔布或美洛昔康）或阻断促炎受体（EP1/EP3）通过减少免疫细胞浸润和细胞因子产生，保护少突胶质细胞，通过COX-2依赖和独立的机制减轻疾病病理。这篇综述讨论了选择性靶向COX-2/PGE2轴（如EP1/EP3信号）的有害影响的潜力，同时保留保护途径作为ms的复杂治疗策略。然而，心血管风险限制了COX-2抑制剂的临床翻译，需要开发更安全，更精确的通路调节。

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引用次数: 0

Development and validation of a flow cytometry-based ISG15 induction assay to monitor the type I interferon response 基于流式细胞术的ISG15诱导试验的开发和验证，以监测I型干扰素反应。

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-12-02 DOI: 10.1016/j.clim.2025.110654

Birthe Michiels , Rudi Beyaert , Jens Staal , Doreen Dillaerts , Maaike Cockx , Glynis Frans , Birgit Timmermans , Natalie Lorent , Isabelle Meyts , Xavier Bossuyt

The type I IFN response plays an important role in the immune defence against invading pathogens and in certain autoinflammatory diseases. In this study, a flow cytometry-based assay to measure ISG15 production in response to stimulation with various TLR ligands and IFNα was developed. PBMCs of healthy controls or patients were stimulated with TLR7/8, TLR3 and TLR9 ligands and IFNα2 whereafter ISG15 expression was measured. The ability of the assay to analyse TLR-dependent type I IFN induction and type I IFN-dependent JAK/STAT activation was verified by inhibition of ISG15 induction by a TBK1/IKKε inhibitor and a JAK1 inhibitor, respectively. TLR7/8 ligand- and TLR9 ligand-induced ISG15 production but not IFNα2-induced ISG15 production was abolished in a patient with AR IRF7 deficiency. IFNα2-induced ISG15 expression was abolished by serum containing neutralizing anti-IFNα2 autoantibodies. The flow cytometry-based ISG15 induction assay can be applied to screen for defects in the type I IFN response.

I型IFN反应在抵抗入侵病原体和某些自身炎症性疾病的免疫防御中起重要作用。在这项研究中，我们开发了一种基于流式细胞术的方法来测量ISG15在各种TLR配体和IFNα刺激下的产生。用TLR7/8、TLR3、TLR9配体和IFNα2刺激健康对照或患者外周血，测定ISG15的表达。通过TBK1/IKKε抑制剂和JAK1抑制剂分别抑制ISG15诱导，验证了该试验分析tlr依赖性I型IFN诱导和I型IFN依赖性JAK/STAT激活的能力。在AR IRF7缺乏的患者中，TLR7/8配体和TLR9配体诱导的ISG15产生被消除，但ifn α2诱导的ISG15产生未被消除。含有中和性抗ifn α2自身抗体的血清可消除ifn α2诱导的ISG15表达。基于流式细胞术的ISG15诱导试验可用于筛选I型IFN反应中的缺陷。

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引用次数: 0

Involvement of CCCTC-binding factor (CTCF) in immunomodulation and epigenetic regulation of T helper cell differentiation during Non-Small Cell Lung Cancer (NSCLC) ccctc结合因子（CTCF）参与非小细胞肺癌（NSCLC）中T辅助细胞分化的免疫调节和表观遗传调控

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-12-31 DOI: 10.1016/j.clim.2025.110662

Oishi Mukherjee , Sayani Bose , Sudeshna Rakshit , Geetha Shanmugam , Anuneha Baranwal , Srawsta Saha , Harsita Goswami , Melvin George , Koustav Sarkar

Recent advances in NSCLC therapy remain limited by treatment resistance, much of which is influenced by epigenetic regulation of immune responses. In this study, we investigate the role of CTCF, a chromatin architectural protein that modulates enhancer–promoter interactions, in shaping T-helper (T_H) cell differentiation and tumor immunity. Changes in CTCF expression coincided with altered chromatin-level enrichment patterns involving DNA repair–associated factors (ERCC1, XPF, CSA) and tumor-related proteins at the IFNG locus, as well as shifts in histone modification marks (H3K4me3 and H3K27me3) at T_H1-associated genes, including TBX21 and IFNG. These chromatin-associated features were accompanied by increased nitric oxide production and enhanced cytotoxicity in functional assays. Collectively, these findings suggest that variation in CTCF levels is linked to coordinated epigenetic and immune-associated changes in NSCLC, supporting its potential relevance as an immuno-epigenetic factor in shaping anti-tumor immune responses.

NSCLC治疗的最新进展仍然受到治疗耐药的限制，其中大部分受免疫反应的表观遗传调控的影响。在这项研究中，我们研究了CTCF（一种调节增强子-启动子相互作用的染色质结构蛋白）在塑造t辅助（TH）细胞分化和肿瘤免疫中的作用。CTCF表达的变化与染色质水平富集模式的改变相一致，涉及DNA修复相关因子（ERCC1， XPF， CSA）和IFNG位点的肿瘤相关蛋白，以及th1相关基因（包括TBX21和IFNG）上组蛋白修饰标记（H3K4me3和H3K27me3）的变化。在功能分析中，这些染色质相关的特征伴随着一氧化氮产生的增加和细胞毒性的增强。总的来说，这些发现表明CTCF水平的变化与NSCLC中协调的表观遗传和免疫相关变化有关，支持其作为形成抗肿瘤免疫反应的免疫-表观遗传因子的潜在相关性。

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引用次数: 0

Clinical prognosis and cancer risk assessment in autoimmune diseases with anti–TIF1γ alone or concurrent with anti–Ro52 antibodies in a Taiwanese cohort 台湾队列中单独使用抗tif1γ或同时使用抗ro52抗体的自身免疫性疾病的临床预后和癌症风险评估

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2026-01-14 DOI: 10.1016/j.clim.2026.110663

Chih-Chun Lee , Li-Chung Chiu , Shih-Ching Lee , Tien-Ming Chan

Objective

Dermatomyositis (DM), a subset of idiopathic inflammatory myopathies, affects the skin and skeletal muscles and is associated with an increased cancer risk, particularly in patients with antibodies against transcriptional intermediary factor 1γ (TIF1γ). This study aimed to evaluate the diagnostic value of anti–TIF1γ antibodies and assess their clinical significance, especially regarding cancer risk and associations with other autoimmune diseases (including overlap syndromes).

Methods

In this multicenter retrospective study, we identified patients with positive anti–TIF1γ tests from Chang Gung Medical Foundation (2019–2021). Anti–TIF1γ and anti–Ro52 antibodies were detected via line blot and fluorescent enzyme immunoassay. Patients were stratified into strong-positive (++/+++) versus weak-positive (+) groups and analyzed for clinical features and cancer prevalence. Data spanned three full years and were statistically evaluated.

Results

Among 84 patients with anti–TIF1γ antibody positivity, 19 (22.6%) were diagnosed with DM, including 15 patients in the strong-positive group and 4 patients in the weak-positive group, and 8 (9.5%) developed malignancy. Strong anti–TIF1γ positivity was significantly linked to dermatomyositis (46.7% vs. 7.4% in weak-positive, p < 0.05) and higher cancer incidence (20.0% vs. 3.7%, p = 0.0221). Moreover, concurrent anti–TIF1γ and anti–Ro52 seropositivity correlated with systemic lupus erythematosus (23.8% vs. 4.8%, p = 0.0211) and SLE–SjS overlap (14.3% vs. 0%, p = 0.0140). Typical skin findings included heliotrope rash, Gottron sign, and periungual telangiectasias; malignancies observed were nasopharyngeal carcinoma and lung cancer in this cohort.

Conclusions

High anti-TIF1γ titers significantly increase dermatomyositis and cancer risk. Concomitant anti-Ro52 was associated with SLE and SLE–SjS overlap, emphasizing the necessity of comprehensive myositis antibody profiling for diagnosis and risk assessment.

目的：皮肌炎（DM）是特发性炎性肌病的一个子集，影响皮肤和骨骼肌，并与癌症风险增加相关，特别是在具有抗转录中介因子1γ (TIF1γ)抗体的患者中。本研究旨在评估抗tif1γ抗体的诊断价值，并评估其临床意义，特别是在癌症风险和与其他自身免疫性疾病（包括重叠综合征）的关联方面。方法：在这项多中心回顾性研究中，我们从长庚医学基金会（2019-2021）筛选了抗tif1γ阳性的患者。通过线印迹和荧光酶免疫分析法检测抗tif1γ和抗ro52抗体。患者被分为强阳性（++/+++）组和弱阳性（+）组，并分析临床特征和癌症患病率。数据跨越了整整三年，并进行了统计评估。结果：84例抗tif1γ抗体阳性患者中，确诊DM 19例（22.6%），其中强阳性组15例，弱阳性组4例，恶性肿瘤8例（9.5%）。强抗tif1γ阳性与皮肌炎显著相关(46.7%对7.4%弱阳性，p 结论：高抗tif1γ滴度显著增加皮肌炎和癌症的风险。伴随的抗ro52与SLE和SLE- sjs重叠相关，强调了全面的肌炎抗体谱分析对诊断和风险评估的必要性。

{"title":"Clinical prognosis and cancer risk assessment in autoimmune diseases with anti–TIF1γ alone or concurrent with anti–Ro52 antibodies in a Taiwanese cohort","authors":"Chih-Chun Lee , Li-Chung Chiu , Shih-Ching Lee , Tien-Ming Chan","doi":"10.1016/j.clim.2026.110663","DOIUrl":"10.1016/j.clim.2026.110663","url":null,"abstract":"<div><h3>Objective</h3><div>Dermatomyositis (DM), a subset of idiopathic inflammatory myopathies, affects the skin and skeletal muscles and is associated with an increased cancer risk, particularly in patients with antibodies against transcriptional intermediary factor 1γ (TIF1γ). This study aimed to evaluate the diagnostic value of anti–TIF1γ antibodies and assess their clinical significance, especially regarding cancer risk and associations with other autoimmune diseases (including overlap syndromes).</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study, we identified patients with positive anti–TIF1γ tests from Chang Gung Medical Foundation (2019–2021). Anti–TIF1γ and anti–Ro52 antibodies were detected via line blot and fluorescent enzyme immunoassay. Patients were stratified into strong-positive (++/+++) versus weak-positive (+) groups and analyzed for clinical features and cancer prevalence. Data spanned three full years and were statistically evaluated.</div></div><div><h3>Results</h3><div>Among 84 patients with anti–TIF1γ antibody positivity, 19 (22.6%) were diagnosed with DM, including 15 patients in the strong-positive group and 4 patients in the weak-positive group, and 8 (9.5%) developed malignancy. Strong anti–TIF1γ positivity was significantly linked to dermatomyositis (46.7% vs. 7.4% in weak-positive, <em>p</em> < 0.05) and higher cancer incidence (20.0% vs. 3.7%, <em>p</em> = 0.0221). Moreover, concurrent anti–TIF1γ and anti–Ro52 seropositivity correlated with systemic lupus erythematosus (23.8% vs. 4.8%, <em>p</em> = 0.0211) and SLE–SjS overlap (14.3% vs. 0%, <em>p</em> = 0.0140). Typical skin findings included heliotrope rash, Gottron sign, and periungual telangiectasias; malignancies observed were nasopharyngeal carcinoma and lung cancer in this cohort.</div></div><div><h3>Conclusions</h3><div>High anti-TIF1γ titers significantly increase dermatomyositis and cancer risk. Concomitant anti-Ro52 was associated with SLE and SLE–SjS overlap, emphasizing the necessity of comprehensive myositis antibody profiling for diagnosis and risk assessment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110663"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remaining molecular scarring in the skin of patients with psoriasis: What are the reversal factors? 银屑病患者皮肤上残留的分子瘢痕：逆转因素是什么？

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-11-24 DOI: 10.1016/j.clim.2025.110645

Parvaneh Hatami , Hamed Nicknam Asl , Zeinab Aryanian , Azadeh Khayyat , Mona Homayouni , Arash Mostaghimi

引用次数: 0

Single-cell sequencing reveals APOE deletion alleviates adipose wasting in cancer cachexia via macrophage repolarization 单细胞测序显示APOE缺失通过巨噬细胞复极化减轻癌症恶病质中的脂肪消耗

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.clim.2025.110660

Jun Han , Qifeng Yao , Qiuyue Huang , Zuoyou Ding , Guohao Wu

Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE^−/− mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.

癌症恶病质包括严重的骨骼肌和脂肪组织损失。载脂蛋白E （ApoE）在脂肪重塑中的作用尚不清楚。本研究探讨了ApoE在癌症恶病质中的作用。我们发现恶病质患者血浆ApoE降低，但皮下脂肪表达升高。在体外实验中，脂肪细胞中ApoE的下调下调了脂肪生成和脂肪分解基因。在体内，ApoE - / -小鼠在恶病质模型中受到脂肪消耗的保护。单细胞RNA测序显示，ApoE缺乏改变了免疫细胞动力学，增加了巨噬细胞总数，并丰富了具有m2样表型的特定Cbr2+巨噬细胞亚群。免疫荧光显示脂肪组织中M2巨噬细胞浸润增强，证实了这一点。我们得出结论，ApoE是癌症恶病质中脂肪稳态和免疫调节的关键调节因子，代表了一个有希望的诊断和治疗靶点。

引用次数: 0

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