Expert Review of Clinical Immunology最新文献

Introduction: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and fibrous components within the arterial wall. While traditionally considered a lipid-driven process, growing evidence suggests that immune mechanisms play a central role in all stages of atherogenesis.

Areas covered: This review summarizes the most relevant evidence supporting the immunoinflammatory basis of plaque development, progression, and destabilization. Both innate and adaptive immune responses contribute to endothelial dysfunction, immune cell recruitment, cytokine production, and the activation of inflammasome pathways, which amplify vascular inflammation. Crucially, the interplay between inflammation and thrombosis, termed thromboinflammation, plays a pivotal role in plaque instability and clinical events.

Expert opinion: We critically examine the limitations of the classic dichotomy between stable and unstable plaques, proposing instead a tripartite classification: active, dormant, and inactive plaques, analogous to the states of volcanic activity. Even clinically 'stable' plaques may exhibit silent yet ongoing immunometabolic and thromboinflammatory activity, contributing to residual cardiovascular risk. Advanced imaging, molecular diagnostics, and inflammation-sensitive biomarkers (e.g. high-sensitivity C-reactive protein, IL-6) can help detect subclinical plaque activity. Finally, the concept of 'thromboinflammaging' emphasizes the impact of age-related immune dysregulation on vascular pathology. This evolving paradigm supports immunomodulation as a cornerstone in precision cardiovascular medicine.

Background: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease characterized by sterile bone inflammation. While monogenic causes are rare and typically present with early-onset, distinct skin or lytic bone lesions, the contribution of COX-pathway genes remains underexplored. TBXAS1 gene variants are classically associated with Ghosal hematodiaphyseal dysplasia (GHDD), which causes osteosclerosis and hematologic abnormalities.

Research design and methods: In this single-center, cross-sectional study, whole-exome sequencing first revealed the TBXAS1 variants in the index case, a 6-year-old boy with multifocal CNO and good clinical response to NSAIDs. Afterward, we performed next-generation sequencing (NGS) of the TBXAS1 gene in a single-center CNO cohort.

Results: Among 16 patients within the CNO cohort, NGS revealed two siblings with the same variants who were also presented with CNO, but without signs of osteosclerosis or hematologic involvement.

Conclusions: These findings suggest a potential link between TBXAS1 deficiency and a distinct, milder CNO phenotype potentially mediated by the COX pathway. However, it remains uncertain whether TBXAS1 mutations define a new CNO subtype or represent an attenuated form of GHDD. Further functional and genetic studies targeting COX-pathway-related genes are needed to clarify the role of TBXAS1 in the pathogenesis of CNO and to identify novel disease mechanisms.

Introduction: Difficult-to-treat psoriatic arthritis (D2T-PsA) is increasingly recognized as a complex clinical entity characterized by persistent disease burden despite multiple targeted therapies. Its identification is essential to improve patient outcomes and to guide the development of new therapeutic strategies.

Areas covered: In this perspective article, we discuss the evolving concept of D2T-PsA, including its epidemiology, clinical characterization, and underlying pathophysiological mechanisms. We highlight the role of gender differences, psychosocial comorbidities, and central sensitization in shaping disease persistence and patient-reported impact. We also examine the limitations of current disease activity indices (DAPSA, PsAID, PASDAS) in capturing heterogeneity and the need for multidimensional frameworks. A structured literature search was conducted in PubMed/MEDLINE and Scopus databases (January 2020-June 2025), restricted to English-language publications, using combinations of the terms psoriatic arthritis, difficult-to-treat, refractory, and difficult-to-manage. Additional references were identified from conference abstracts and relevant bibliographies.

Expert opinion: Recognizing D2T-PsA as a distinct, multifactorial entity is critical to advancing personalized medicine. Future directions will involve harmonizing EULAR and GRAPPA frameworks, integrating biomarker discovery, digital tools, and adaptive trial designs, and embedding patient perspectives. This multidimensional approach is expected to transform treatment from empirical cycling toward precision care in psoriatic arthritis.

Introduction: In inflammatory bowel diseases (IBD), human intestinal myofibroblasts (HIMF) gets activated due to chronic inflammation and start accumulating excessive extracellular matrix (ECM). ECM drives the significant clinical problem of intestinal fibrosis and stricture formation in Crohn's disease (CD) and Ulcerative colitis (UC) patients that require surgical intervention in a large group of the population.

Areas covered: In this review, we delineate the role of transglutaminase 2 (TG2), a matrix bound, calcium (Ca) dependent enzyme, as an important effector in the pathogenesis of chronic inflammatory diseases. We discuss the role of TG2 in fibrotic diseases with a focus on intestinal fibrosis and TG2 as a potential target for therapy of stricturing CD. This review additionally covers the progress in our mechanistic understanding of TG2 as a marker and driver for intestinal fibrosis and stricture formation in IBD patients.

Expert opinion: TG2 may play a central role in promoting inflammation independent progression of fibrosis, potentially explaining the lack of efficacy of traditional anti-inflammatory drugs in fibrotic diseases. The anti-fibrotic potential of TG2 specific inhibitors in stricturing Crohn's disease are just starting to be explored. Further investigations are needed to identify novel mechanisms for TG2 specific inhibitors in the intestine.

Introduction: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by dense lymphoplasmacytic infiltration and storiform fibrosis, often resulting in organ dysfunction. Although glucocorticoids provide initial clinical improvement, relapse is common, underscoring the need for targeted therapies. B-cell depletion therapy has emerged as a promising approach, shedding light on the roles of plasmablasts and cytotoxic T lymphocytes in disease pathogenesis.

Areas covered: This review summarizes recent advances in immunological mechanisms of IgG4-RD, focusing on plasmablasts, activated B cells, cytotoxic T lymphocytes, T follicular helper (Tfh) cells, macrophages, dendritic cells, other immune cells, and fibroblasts. We highlight how single-cell RNA sequencing and highly multiplex immunofluorescence have uncovered novel immune subsets and their interactions. These technologies have identified previously unrecognized populations, including GZMK⁺ cytotoxic Tfh cells, MKI67⁺ B cells, and double-negative type 3 B cells, offering unprecedented resolution into disease mechanisms.

Expert opinion: Single-cell technologies have revolutionized our understanding of IgG4-RD immunopathogenesis and potentially revealed disease heterogeneity across clinical phenotypes. These insights hold promise for biomarker development and precision therapeutic strategies. Future directions should include spatial transcriptomics and proteomics, improved animal models, and translational efforts to bridge mechanistic discoveries with targeted treatment for this complex multi-organ disease.

Background: Aims of this study were to evaluate the serum level of autoantibodies against G-protein-coupled receptors for Angiotensin II type 1 (anti-AT1R) and endothelin receptor type A (anti-ETAR) in systemic sclerosis (SSc) patients and healthy controls (HC) and to evaluate the associations of these antibodies with microvascular complication of SSc, such as digital ulcers (DUs), subclinical renal vasculopathy and early pulmonary vasculopathy.

Research design and methods: Sixty-four SSc patients and 20 HC were tested for anti-AT1R and anti-ETAR.

Results: SSc patients had higher anti-AT1R [7.78 ng/ml (IQR 6.14;12.16) vs 3.25 ng/ml (IQR 2.60;4.70), p < 0.001] and anti-ETAR [0.16 OD (IQR 0.14;0.17) vs 0.10 OD (IQR 0.10;0.12), p < 0.001] than HC. SSc patients with DUs had higher anti-AT1R [10.79 ng/ml (IQR 7.32;14.15) vs 6.76 ng/ml (IQR 5.88;7.88), p < 0.001] and anti-ETAR [0.16 OD (IQR 0.15;0.18) vs 0.15 OD (IQR 0.13;0.16), p < 0.01] than SSc patients without DUs. We found a positive correlation between renal resistive index (RRI) and anti-AT1R (r = 0.357, p < 0.01) or anti-ETAR (r = 0.442, p < 0.001) and a negative correlation between tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/sPAP) and anti-AT1R (r = -0.436, p < 0.001) or anti-ETAR (r =  -0.334, p < 0.01).

Conclusions: Anti-AT1R and anti-ETAR may play a pathogenic role in endothelial dysfunction.

Objective: This study evaluated the potential diagnostic utility of pepsin, trypsin, and mucin 5B (MUC5B) in hearing impairment in patients with laryngopharyngeal reflux (LPR)-related chronic secretory OM (CSOM).

Methods: Patients with LPR-related CSOM were enrolled and assigned into the normal hearing (NH), and mild (Mi-HI) and moderate-to-severe hearing impairment (Mo-HI) groups. Pepsin, trypsin, and MUC5B contents were determined by ELISA, with their correlations with Eustachian tube dysfunction questionnaire-7 (ETDQ-7) score and inflammatory factors (interleukin [IL]-2, IL6, IL-8), and diagnostic performance in hearing impairment assessed by Pearson, Spearman, and ROC curves. Factors influencing hearing impairment were identified using logistic regression models.

Results: Pepsin, trypsin, and MUC5B contents were upregulated in patients' middle ear effusion as hearing impairment worsened. The three indicators correlated to EDTQ-7 and inflammatory factors, and exhibited high diagnostic value for hearing impairment in LPR-related CSOM patients. Remarkably, their combination created significantly higher diagnostic value than a single indicator. Abundantly-increased pepsin, trypsin, and MUC5B amplified hearing impairment incidence.

Conclusion: Pepsin, trypsin, and MUC5B are independent risk factors for hearing impairment in LPR-related CSOM patients. Their combination assists hearing impairment diagnosis in patients, providing a tool in clinical practice to stratify patients and offering a theoretical basis for exploring therapeutic targets.

Background: Periostin is a novel biomarker associated with a range of inflammatory conditions, particularly those involving pulmonary inflammation and fibrotic processes. This research aimed to investigate the association between periostin concentrations, severity of COVID-19, and patient mortality.

Research design and methods: Our study comprised 127 participants: 36 healthy controls (Group-1), 37 COVID-19 patients with uncomplicated disease (Group-2), 28 with mild pneumonia (Group-3), and 26 with severe pneumonia (Group-4). Periostin levels in all participants were measured using the ELISA method.

Results: Periostin concentrations were significantly elevated in COVID-19 patients compared to healthy controls (p < 0.001). Periostin concentrations were significantly elevated in patients with severe COVID-19 pneumonia compared to those with mild pneumonia or uncomplicated disease (p < 0.05). According to our study analysis, periostin level independently predicted severe pneumonia in COVID-19 (Odds Ratio: 1.085; 95% CI: 1.035-1.137; p = 0.001). Serum periostin threshold of 67.5 ng/mL predicted severe pneumonia with 69.2% sensitivity and 66.2% specificity. Lastly, every 1 ng/mL increase in periostin was linked to 1.21-fold higher mortality risk in COVID-19 patients with severe pneumonia (Hazard Ratio: 1.216; 95% CI: 1.006-1.471; p = 0.044).

Conclusion: Our findings suggest that periostin level may help assessing disease severity and predicting mortality in COVID-19. Additional studies with expanded patient groups are needed.

Introduction: In patients with cirrhosis and ascites, failure of intestinal barriers and cirrhosis-associated immune dysfunction contribute to the translocation of bacteria and microbial products to the peritoneal cavity, which promotes infection, perpetuates inflammation and accelerates acute-on-chronic liver failure. Resident peritoneal immune cells are repeatedly exposed to bacterial products, and their activation status is linked to complications of spontaneous bacterial peritonitis.

Areas covered: This narrative review summarizes the recent research on human peritoneal immunity in decompensated cirrhosis, focusing on the altered composition and functional states of human peritoneal macrophages, resident and migrating T cells, and neutrophils and their involvement in peritoneal inflammation and infection.

Expert opinion: Peritoneal immune cells in decompensated cirrhosis show compartmentalized chronic activation and dysfunction, contributing to inflammation and infection risk. Given the direct accessibility of these cells, targeting peritoneal macrophage priming and differentiation, innate immune memory, inflammatory mediators and intercellular peritoneal cross-talk offer potential strategies to prevent infections and mitigate inflammation. To fine-tune the delicate balance between hyperinflammation and anergy, further research is necessary to translate immunomodulatory approaches into effective clinical interventions.