Journal of inflammation research

Background: Bullous pemphigoid (BP), an autoimmune blistering disorder that primarily afflicts the geriatric population, poses diagnostic and therapeutic challenges, particularly in patients with comorbidities. This retrospective study aimed to identify and validate potential adjunctive tissue biomarkers for BP and explore their association with immune-related mechanisms through integrated bioinformatics analysis and experimental validation. Methods: Transcriptomic data from the GEO dataset were analyzed to identify differentially expressed genes (DEGs), which were further cross-referenced with immune-related gene signatures. CD74 was selected as a candidate biomarker and its expression was validated by immunohistochemistry (IHC) in paraffin-embedded skin tissues from patients with BP, healthy controls (HC), and disease controls, including pemphigus vulgaris (PV), psoriasis (Pso), atopic dermatitis (AD), and systemic lupus erythematosus (SLE). Diagnostic performance was evaluated by ROC curve analysis. Single-cell RNA sequencing and immunofluorescence staining were performed to investigate the cellular distribution and immune association of CD74. Results: CD74 was identified as an immune-related DEG associated with CCL13 expression. CD74 expression was increased in BP lesions and exhibited a characteristic linear distribution along the dermoepidermal junction. Quantitative ROC analysis based on CD74 expression area percentage showed moderate diagnostic performance, while the linear staining pattern demonstrated potential value as an adjunctive diagnostic feature. Single-cell RNA sequencing revealed predominant CD74 expression in MHC-II-enriched cells, and immunofluorescence confirmed CD74/HLA-DR colocalization. CD74 expression was positively correlated with peripheral blood eosinophil counts, suggesting an association with systemic immune activation in BP. Conclusion: CD74 may represent a promising adjunctive tissue biomarker for BP diagnosis. Its characteristic tissue distribution and association with immune-related features suggest that CD74 may reflect immune alterations within BP lesions. Further validation in larger independent cohorts is required.

Kirby N Gilpin,1,2 Bann Khraisat,3 Saif I Hejazi,4 Saud B Harahsheh,4 Simon Lee,5 Ashraf S Harahsheh1,2 1Division of Cardiology, Heart Research Institute, Children’s National Hospital, Washington, DC, USA; 2Department of Pediatrics, George Washington University School of Medicine & Health Sciences, Washington, DC, USA; 3General Practice, Eye Specialty Hospital, Amman, Jordan; 4School of Medicine, University of Jordan, Amman, Jordan; 5Division of Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USACorrespondence: Ashraf S Harahsheh, Division of Cardiology, Department of Pediatrics, Heart Research Institute, George Washington University School of Medicine & Health Sciences, Children’s National Hospital, 111 Michigan Ave, NW, Washington, DC, 20010, USA, Tel +1-202-476-2020, Fax +1-202-476-5700, Email aharahsh@childrensnational.orgAbstract: Kawasaki Disease (KD) is now recognized as the global leading cause of acquired heart disease in children. The purpose of this review is to provide an overview of what is known about KD etiology, its management strategies and sequelae, and to discuss the inflammatory pathophysiology, specifically cardiac inflammation and development of coronary artery aneurysms (CAA) in KD and how this compares with other childhood inflammatory disorders. While the presentation of KD and its cardiovascular sequelae is unique, there is overlap in the pathophysiology of other pediatric inflammatory vasculopathies. As we understand and learn more about KD, there is opportunity for further discovery of effective treatments which may have implications in other pediatric inflammatory conditions.Keywords: cardiology, inflammation, immunology, Kawasaki, acquired heart disease

Jiawen Chen,1– 6,&ast; Rongying Chen,1– 6,&ast; Beiqi Lin,1– 6,&ast; Yucheng Xu,1– 6 Shi-Fan Ruan,7 Meiling Chen,8 Niu Xiang,1– 6 Ying Zou,1– 6 Hui Ke,1– 6 Mengting Lin,1– 6 Zhixun Xiao,1– 6,&ast; Bo Cheng1– 6,&ast; 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 2Department of Dermatology Aoti Campus of The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350002, People’s Republic of China; 3Fujian Provincial Clinical Research Center for Immune Skin Diseases, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 4Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 5Key Laboratory of Skin Cancer of Fujian Higher Education Institutions, The Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 6Fujian Dermatology and Venereology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350000, People’s Republic of China; 7School of Medicine, Fuzhou University, Fuzhou, Fujian, 350108, People’s Republic of China; 8Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixun Xiao, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email zhixun@fjmu.edu.cn Bo Cheng, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, Fujian, 350000, People’s Republic of China, Email chengbo630415@126.comBackground: Generalized pustular psoriasis (GPP) is a severe neutrophilic inflammatory disease. Although biologics targeting IL-17A, IL-12/23, and IL-36R are used in clinical practice, their relative effectiveness in real-world has not been fully characterized, and the potential value of plasma MMP9 as a biomarker of disease activity remains unclear.Objective: To compare differences in efficacy and safety among biologics targeting IL-17A, IL-12/23, and IL-36R, and to evaluate changes in treatment-related plasma MMP9 levels and their association with disease activity and routine laboratory markers. Additionally, to characterize the cellular expression patterns of MMP9 in GPP lesions using single-cell transcriptomic analysis.Methods: This retrospective study included patients with GPP who received IL-17A, IL-12/23, or IL-36R inhibitors between July 2019 and May 2025. Clinical outcomes were evaluated over 24 weeks. Plasma MMP9 levels were measured longitudinally and correlated with clinical activity and inflammatory markers. Single-cell RNA sequencing of GPP lesions was performed to characterize the cellular expression pattern of MMP9.Results: A total of 72 patients were included in the clinical effectiveness analysis. After 24 weeks, GPP Area and Severity Index (GPPASI), GPP physician global assessment (GPPGA), and Dermatology Life Quality Index (DLQI) improved significantly from baseline, with IL-36R inhibitors showing the most rapid response, followed by IL-17A and IL-12/23 inhibitors. In patients with available plasma samples (n=13), baseline MMP9 showed the strongest observed correlation with GPPASI among the assessed index (Spearman’s r = 0.8736, P< 0.001), whereas the correlations of GPPASI with C-reactive protein (CRP), white blood cell count (WBC), neutrophil count, and albumin were relatively weak. Single-cell RNA sequencing revealed predominant MMP9 expression in myeloid cells, particularly neutrophils and macrophages.Conclusion: Biologics targeting IL-36R, IL-17A, and IL-12/23 provided sustained disease control in GPP. Circulating MMP9 was strongly associated with GPPASI, decreased following biologic treatment, and exhibited a predominantly myeloid expression pattern in GPP lesions, supporting its further evaluation as a candidate disease-activity biomarker.Keywords: generalized pustular psoriasis, biologics, matrix metalloproteinase 9, real-world study, biomarker

Wei Luo,1,2,&ast; Lei-lei Duan,1,3,&ast; Can Ding,1 Ting Li,1 Shan-tong Yan,1 Wen-bing Zeng,2 Zhi-gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 3Department of Radiology, People’s Hospital of Chongqing Liangjiang New Area, Chongqing, 401120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-gang Chu, Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1&num; Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, People’s Republic of China, Tel +86 18723032809, Fax +86 23 68811487, Email chuzg0815@163.comPurpose: Part-solid nodules (PSNs) are more likely to be malignant, especially those with multiple solid components (SCs). In contrast, PSNs with a single SC are more frequently encountered in clinical practice, yet they have not been investigated separately, and accurate differentiation of these lesions remains challenging. This study aims to identify the clinical and computed tomography (CT) characteristics of non-neoplastic single-SC PSNs.Methods: This two-center retrospective study enrolled 195 non-neoplastic single-SC PSNs and 309 neoplastic ones between June 2022 and January 2025. Surgical pathology was used to confirm neoplastic lesions, while non-neoplastic lesions were verified by surgical pathology or imaging follow-up. The patients’ clinical characteristics and the CT features of lesions and SCs were reviewed and compared. Multivariable logistic regression analysis was performed to identify the independent predictors of non-neoplastic lesions.Results: For non-neoplastic single-SC PSNs, the independent predictors comprised one nodule-level feature and four SC-level features. The nodule-level predictor was ill-defined boundary (odds ratio [OR]: 10.380, 95% confidence interval [CI]: 6.212– 17.342, P < 0.001). SC-level predictors included central distribution (OR: 3.862, 95% CI: 2.267– 6.582, P < 0.001), regular shape (OR: 1.729, 95% CI: 1.044– 2.864, P = 0.037), small SC (consolidation tumor ratio [CTR] ≤ 0.5) with well-defined boundary (OR: 2.319, 95% CI: 1.322– 4.067, P = 0.010), and lower attenuation difference between the SC and peripheral ground-glass opacity (GGO) (ΔCT(SC-GGO)) (OR: 1.007, 95% CI: 1.004– 1.014, P = 0.002). The model achieved an area under the curve of 0.905 (95% CI: 0.880– 0.930, P < 0.001), with a sensitivity of 80.5% and a specificity of 86.7%. Bootstrap internal validation yielded an optimism-corrected AUC of 0.886.Conclusion: Ill-defined single-SC PSNs featuring centrally distributed, regular, small (CTR ≤ 0.5) and well-defined SCs, along with a lower ΔCT(SC-GGO), are indicative of non-neoplastic lesions. These findings may support more conservative management and imaging follow-up in appropriately selected patients. However, external validation is required before clinical application.Keywords: part-solid nodule, single solid component, non-neoplastic, neoplastic, computed tomography

Shixuan Hua,1– 3,&ast; Dong Cen,4,6,&ast; Jing Guo,1– 3 Jiao Zhang,5 Chenchen Si,1– 3 Poshi Xu,1– 3 Ailan Zhang,2 Leichao Wang1– 3 1Department of Laboratory Medicine, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Laboratory Medicine, Heart Center of Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Laboratory Medicine, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Laboratory Medicine, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 5School of Laboratory Medicine, Wenzhou Medical University Ningbo Campus, Ningbo, Zhejiang, People’s Republic of China; 6Ningbo Key Laboratory of Precision Integrated Prevention and Treatment of Comorbidities in Steatotic Liver Disease, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shixuan Hua, Email 15838083903@zzu.edu.cn Leichao Wang, Email wanglc503@163.comBackground: Coronary heart disease (CHD) remains the leading cause of global cardiovascular mortality. T cell-mediated adaptive immunity, particularly Th1, regulatory T cell (Treg), and Th17 subsets, plays a pivotal role in atherosclerotic plaque formation and destabilisation, yet a systematic, quantitative mapping of this research landscape is lacking.Methods: Publications on T cell immunity in CHD from 1991 to August 2026 were retrieved from the Web of Science Core Collection, restricted to English-language original articles. Bibliometric indicators were analysed with Microsoft Excel, VOSviewer (v1.6.20), CiteSpace (v6.4.R1), and bibliometric.com. Co-authorship, keyword co-occurrence, and burst-keyword analyses were performed.Results: A total of 761 articles from 5,796 authors across 58 countries/regions and 299 journals were identified. Annual output increased markedly after 2010. China contributed the largest number of articles (n = 255, 33.5%), while the USA led in total citations (n = 8552), followed by China (n = 6,965) and Germany (n = 4,110). The most prolific and most highly cited author was Hansson Goran K. (14 publications; H-index = 13), while Becker AE achieved the highest average citation impact (248.0 citations per article). Circulation (IF = 35.5) was the leading journal by both article count (n = 33) and citations (n = 2,725). Keyword clustering revealed eight major research themes: clinical translation and computational approaches, T cell activation and immune cell interactions, classic immunopathology and plaque biology, inflammation and infectious triggers, Treg biology and T helper subsets, cytokine regulation and apoptosis, plaque vulnerability and ACS, and antigen presentation and extracellular vesicles. Burst analysis identified “machine learning”, “monocytes”, and “risk” as the most prominent emerging topics since 2023.Conclusion: Research on T cell immunity in CHD has grown markedly, with a clear shift toward the macrophage–T cell immune axis and immune-metabolic interactions, together with Treg-based therapeutic strategies and machine learning-assisted risk stratification. These findings provide a descriptive map that may help inform future translational research.Keywords: coronary heart disease, T cells, atherosclerosis, machine learning, immune inflammation