Immunologic Research[JOURNAL]
Sun
200 papers
Correction: Association of HLA-B alleles with Familial mediterranean fever (FMF): A comparative study.
Aksu U, Kılıçle PA, Gönen S
Immunol Res · 2026 Jan · PMID 41553628 · Publisher ↗
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Single-cell atlas of axial skeletal immune-matrix interaction in spondylitis.
Wang S, Xu M, Zhang P … +2 more , Hu P, Yang Y
Immunol Res · 2026 Jan · PMID 41537924 · Publisher ↗
Axial skeletal involvement is central to ankylosing spondylitis, yet the in situ interplay between immune effectors (especially cytotoxic T lymphocytes) and the bone matrix microenvironment remains poorly resolved. Prior...
Axial skeletal involvement is central to ankylosing spondylitis, yet the in situ interplay between immune effectors (especially cytotoxic T lymphocytes) and the bone matrix microenvironment remains poorly resolved. Prior single-cell studies in peripheral compartments revealed exhaustion-resistant CTLs and dysregulated transcriptional regulators (e.g. NFKB, FOS, JUN) in AS patients, but lacked spatial and stromal context. We obtained axial skeletal tissue (vertebral bone marrow, enthesial fibrocartilage, adjacent endplate stromal tissue) from 24 AS patients with active disease and 12 age-matched controls undergoing spine surgery (total 108,752 single cells). We performed joint single-cell RNA-seq and ATAC-seq on matched samples, followed by integrative clustering, differential gene expression, chromatin accessibility analysis, pseudotime trajectories, and ligand-receptor network inference. Correlations with clinical indices (BASDAI, MRI inflammation scores) and imaging structural progression were assessed. We identified a discrete CTL subset in axial tissues with high expression of checkpoint molecules (PD-1, TIM-3), cytotoxic genes (GZMB, PRF1), and chromatin accessibility favoring NFKB/FOS motif enrichment, consistent with resistance to exhaustion. This subset increased by about 2.8 times in AS compared to controls (p < 0.001). Simultaneously, enthesial stromal fibroblasts displayed the upregulation of matrix remodeling genes (MMP9, COL1A1, COL3A1) and osteogenic drivers (RUNX2, BMP2). Ligand-receptor modeling demonstrated robust interactions between CTLs and stromal fibroblasts via TNF, TGFβ, integrin, and Notch signaling pathways. It is important to note that CTL-stromal interaction scores were related to MRI inflammation grade (r = 0.62, p = 0.003) and structural progression (r = 0.54, p = 0.01). This integrated single-cell atlas identifies a pathogenic CTL-stromal axis in the axial skeleton of AS patients, linking immune cytotoxic mechanisms with matrix remodeling and osteogenesis. These findings delineate actionable molecular crosstalk nodes that could inform precision therapeutic strategies aimed at immune-matrix interactions in situ.Clinical trial numberNot applicable.
mRNA-Encoded antibodies as a next-generation therapeutic paradigm: a rapid and adaptive platform for the prevention and treatment of emerging and re-emerging infectious diseases - A critical review.
Singh D
Immunol Res · 2026 Jan · PMID 41521363 · Publisher ↗
Messenger RNA (mRNA)-encoded antibodies represent a transformative therapeutic platform with the potential to rapidly combat emerging infectious diseases by enabling in situ expression of potent neutralizing antibodies d...
Messenger RNA (mRNA)-encoded antibodies represent a transformative therapeutic platform with the potential to rapidly combat emerging infectious diseases by enabling in situ expression of potent neutralizing antibodies directly in the patient's body. Unlike conventional monoclonal antibody (mAb) therapies, which rely on labor-intensive and time-consuming cell culture production, mRNA-encoded antibodies offer a faster, scalable, and cell-free approach that bypasses protein purification and cold-chain constraints. This strategy has demonstrated considerable promise during the COVID-19 pandemic, where Moderna's mRNA-1940, an mRNA-based neutralizing antibody targeting the SARS-CoV-2 spike protein, entered preclinical and early-phase trials within months of viral emergence, underscoring the potential for rapid response in outbreak settings. The platform leverages advances in nucleoside-modified mRNA, codon optimization, and lipid nanoparticle (LNP) delivery systems to achieve transient, high-level expression of functional antibodies with reduced innate immune activation. Beyond COVID-19, mRNA-encoded antibody approaches have been explored in preclinical models of Zika virus, Ebola virus, and rabies, where a single intramuscular dose provided prophylactic and therapeutic benefits in animal models. As the world faces recurrent viral threats, the development of mRNA-encoded antibodies as a plug-and-play system offers a compelling, adaptable, and clinically feasible strategy for infectious disease preparedness. This review explores the mechanistic foundation, delivery technologies, translational progress, case studies, safety considerations, and future clinical potential of mRNA-encoded antibodies in combating both pandemic and endemic infections.
Current and projected trends in rheumatoid arthritis among postmenopausal women in the U.S.: a population-based analysis of the Global Burden of Disease Study 2021, with projections to 2035.
Liu W, Mo X, Xu S
Immunol Res · 2026 Jan · PMID 41518472 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a high prevalence among postmenopausal women (PMW), and it is associated with substantial functional impairment and reduced quality of life. To...
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a high prevalence among postmenopausal women (PMW), and it is associated with substantial functional impairment and reduced quality of life. To inform targeted prevention strategies for high-risk populations in the U.S., a comprehensive and up-to-date assessment of disease burden in this population is needed. We conducted a quantitative analysis of the prevalence, years lived with disability (YLDs), and disability-adjusted life years (DALYs) of RA among PMW (PMWRA) in the U.S. from 1990 to 2021. In addition, disease trends were projected for 2022-2035 using data from the Global Burden of Disease Study (GBD) 2021. We extracted state-level estimates of prevalence, YLDs, and DALYs for PMWRA across 51 U.S. states from 1990 to 2021. Temporal trends were summarized using the average annual percent change (AAPC), and geographic and age-specific differences were assessed. Major risk factors contributing to state- and age-specific YLDs and DALYs were analyzed. Future projections were forecast using autoregressive integrated moving average (ARIMA) and exponential smoothing state-space (ETS) models. All analyses were conducted using R version 4.4.2 and the Joinpoint Regression Program. From 1990 to 2021, prevalence, YLD, and DALY rates among U.S. PMWRA showed upward trends, with AAPCs of 0.55, 0.50, and 0.04, respectively; the corresponding total percent changes in numbers were 1.13, 1.10, and 0.82. In 2021, Montana exhibited the highest prevalence (2,235.76), YLD (277.29), and DALY rates (362.62) among all states nationwide. The disease burden increased with the rising sociodemographic index up to a threshold and then declined. Age-stratified analyses indicated increasing prevalence, YLD, and DALY rates across nearly all age groups. Smoking emerged as the principal risk factor for PMWRA-related YLDs and DALYs across ages and regions. Forecasts based on ARIMA and ETS models indicated continued increases in prevalence and YLDs, whereas DALY rates were projected to decline. The burden of PMWRA among U.S. women is projected to continue rising, with concentration in specific states and age groups, which emphasizes the need for targeted public-health interventions to mitigate the burden in this population.
Comparative disease burden and trends of autoimmune diseases in China and G20 countries: an analysis of the global burden of disease study 2023.
Qin R, Lai X, Qin Q … +2 more , Xu W, Chen L
Immunol Res · 2026 Jan · PMID 41511588 · Publisher ↗
Autoimmune diseases (ADs) represent a growing global public health burden. However, there is still a lack of systematic comparison of long-term epidemiological trends of ADs between China and the Group of Twenty (G20) na...
Autoimmune diseases (ADs) represent a growing global public health burden. However, there is still a lack of systematic comparison of long-term epidemiological trends of ADs between China and the Group of Twenty (G20) nations. Therefore, this study aims to systematically compare the disease burden and long-term trends of autoimmune diseases between China and G20 countries, to inform targeted public health strategies. Using data from the Global Burden of Disease Study 2023, we extracted estimates for rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), and psoriasis (PS) from 1990 to 2023. Age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs), as well as absolute DALYs numbers, were analyzed. Estimated annual percentage change (EAPC) and joinpoint regression were employed to assess temporal trends and identify significant change points. From 1990 to 2023, age-standardized DALY rates (ASDR) declined in both China and the G20 for IBD (China EAPC: -2.78; G20 EAPC: -0.58), MS (China: -1.26; G20: -0.22), and RA (China: -0.22; G20: -0.05), but increased for psoriasis (China: 1.06; G20: 0.69). Despite declining rates, absolute DALYs rose substantially for most diseases. The burden peaked in middle-aged and older adults (55–74 years) and was generally higher among females. Joinpoint analysis revealed heterogeneous multi-stage trends; for instance, China’s IBD ASDR plummeted between 2004 and 2014 (Annual Percent Change, APC: -5.26). Comparative risk analysis showed that in 2023, the proportion of RA DALYs attributable to smoking was higher in China than in the G20 (8.91% vs. 6.96%), driven by a large disparity in males (22.94% vs. 15.88%). In both China and the G20, the overall ASDR of most autoimmune diseases declined between 1990 and 2023, with inflammatory bowel disease showing estimated annual percentage changes of -0.58 and − 2.78, respectively. However, the absolute disease burden increased substantially. Epidemiological analyses revealed pronounced gender disparities, such as a 22.94% smoking-attributed rheumatoid arthritis burden in Chinese males compared to 1.90% in females, and divergent multi-phase temporal trends between regions. These findings highlight both shared and distinct public health challenges, underscoring the need for tailored interventions guided by precise burden metrics and risk factor profiles to mitigate the growing global impact of these conditions.
Association of HLA-B alleles with familial mediterranean fever (FMF): A comparative study.
Aksu U, Kılıçle PA, Gönen S
Immunol Res · 2026 Jan · PMID 41507402 · Publisher ↗
OBJECTIVE: Familial Mediterranean Fever (FMF) is the most prevalent monogenic autoinflammatory disorder. In the present study, we investigated whether HLA-B polymorphisms contribute to familial Mediterranean fever (FMF)...
OBJECTIVE: Familial Mediterranean Fever (FMF) is the most prevalent monogenic autoinflammatory disorder. In the present study, we investigated whether HLA-B polymorphisms contribute to familial Mediterranean fever (FMF) susceptibility and phenotypic variability. METHODS: We enrolled 50 familial Mediterranean fever (FMF) patients, 40 asymptomatic Mediterranean FeVer (MEFV) mutation carriers, and 50 healthy controls. HLA-B genotypes were determined by the PCR-SSO technique. Allele frequencies were compared using chi-square or Fisher's exact tests. RESULTS: HLA-B*51 and HLA-B*35 alleles were enriched among FMF patients compared with controls (p = 0.01 and p = 0.03, respectively). HLA-B*27 was moderately increased in patients (p = 0.04), while HLA-B*44 tended to be more common in carriers (p = 0.07). Odds ratio (OR) and confidence interval (CI) analyses indicated an elevated FMF risk for carriers of HLA-B*51 and HLA-B*35. CONCLUSION: HLA-B variants, particularly B*51 and B*35, may act as immunogenetic modifiers of FMF, supporting the concept of MHC class I linked inflammatory pathways contributing to disease heterogeneity.
SALL4-targeted therapeutic peptide PEN-FFW suppresses PD-L1 and enhances CD8⁺ T cell cytotoxicity via regulating PI3K/AKT signaling in breast cancer.
Xu R, Lan H, Zhang L … +1 more , Che H
Immunol Res · 2026 Jan · PMID 41498967 · Publisher ↗
SALL4 is aberrantly reactivated in multiple malignancies, including breast cancer (BC), where it promotes tumor progression and therapy resistance. However, its therapeutic targeting remains underexplored. This study inv...
SALL4 is aberrantly reactivated in multiple malignancies, including breast cancer (BC), where it promotes tumor progression and therapy resistance. However, its therapeutic targeting remains underexplored. This study investigates the antitumor efficacy of a novel SALL4-inhibitory peptide, PEN-FFW, and its regulatory impact on the PI3K/AKT/PD-L1 axis and CD8⁺ T cell-mediated cytotoxicity in BC. SALL4 expression in BC was assessed using public databases and validated in cell lines by RT-qPCR and western blot. The interaction between SALL4 and the NuRD complex was evaluated by co-immunoprecipitation assay. Functional assays were conducted to assess the effects of PEN-FFW in vitro. Co-culture systems were used to evaluate CD8⁺ T cell-mediated cytotoxicity. Mechanistic studies investigated the involvement of the PTEN/PI3K/AKT/mTOR signaling axis. In vivo efficacy was tested in allograft mouse models, including combination therapy with anti-PD-L1 antibody. SALL4 was significantly upregulated in BC and associated with poor prognosis. PEN-FFW disrupted the SALL4-NuRD interaction, restored PTEN expression, and suppressed PI3K/AKT/mTOR signaling. This led to a reduction in PD-L1 expression and increased apoptosis, while inhibiting the proliferation and migration of BC cells. PEN-FFW also enhanced CD8⁺ T cell cytotoxicity by reducing PD-L1-mediated immune evasion. Furthermore, combination treatment with PEN-FFW and anti-PD-L1 antibody showed superior tumor suppression and increased CD8⁺ T cell infiltration compared to either treatment alone. PEN-FFW is a potent SALL4-inhibitory peptide that suppresses BC progression by downregulating PD-L1 through PI3K/AKT pathway inactivation and promoting CD8⁺ T cell-mediated tumor killing. These findings highlight a promising strategy for enhancing immunotherapy in SALL4-positive BC.
Regional variation in serum ficolin levels and their association with disease activity and clinical manifestations in systemic lupus erythematosus (SLE) patients from India.
Rai K, Khatri R, Jose A … +39 more , Upadhaya D, Singh SR, Lyting K, Husulu, Konkar H, Tapase P, Nadkar M, Rajadhyaksha A, Jaiswal P, Pawaskar S, Chougule D, Sharma A, Saikia L, Phukan C, Deori A, Talukdar L, Laifangbam S, Devi PV, Leishangthem J, Singh YR, Lyngdoh WV, Barman B, Lyngdoh M, Dey B, Lanong S, Shadap C, Wankhar B, Khamo V, Hutsulu, Vanlalruati K, Rhutso Y, Pochury AT, Savino K, Peter CL, Kuotsu N, Kesiezie N, Padwal V, Madkaikar M, Pradhan V
Immunol Res · 2026 Jan · PMID 41483420 · Publisher ↗
The lectin pathway, activated by ficolins, contributes to systemic lupus erythematosus (SLE) pathogenesis, but ficolin data remain inconsistent across populations. Present muti-centric cross-sectional study assessed seru...
The lectin pathway, activated by ficolins, contributes to systemic lupus erythematosus (SLE) pathogenesis, but ficolin data remain inconsistent across populations. Present muti-centric cross-sectional study assessed serum ficolin-1, -2, and - 3 levels and their associations with clinical features and disease activity among SLE patients from five Indian regions (Mumbai, Assam, Meghalaya, Manipur, and Nagaland). Serum levels of ficolin-1, ficolin-2, and ficolin-3 were measured using ELISA. Disease activity was assessed using the SELENA-SLEDAI score. Statistical analyses were performed using non-parametric tests, with p < 0.05 considered significant. Serum ficolin levels differed significantly by region. Ficolin-1 and ficolin-2 levels were positively correlated with the renal involvement in SLE patients from Mumbai (r = 0.218; p < 0.001 and r = 0.199; p = 0.001, respectively), while ficolin-1 levels were also correlated with lupus nephritis (LN) in SLE patients from Manipur (r = 0.247; p = 0.040). In Assam, ficolin-2 levels were significantly reduced in patients with mucocutaneous manifestations (r=-0.258; p = 0.014), and ficolin-3 levels showed a negative correlation with musculoskeletal manifestations (r=-0.217; p = 0.040). In Mumbai, ficolin-1 levels were positively associated with disease activity (r = 0.139; p = 0.018), and ficolin-3 levels correlated positively with anti-dsDNA autoantibodies (r = 0.172; p = 0.004). Conversely, ficolin-3 levels showed a negative correlation with anti-dsDNA (r=-0.470; p < 0.001) in Assam. The present study demonstrated significant regional variations in ficolin levels among SLE patients across India. Association of ficolin-1 and ficolin-3 with specific organ involvement suggested their potential as possible immunological indicators in SLE. These findings suggested the importance of considering regional and ethnic differences in SLE management and warranted further validation through larger, longitudinal studies.
Idiopathic hypertrophic pachymeningitis masquerading as CNS neoplasm: case report and literature review.
Balasubramanian K, Patel P, Fassina GR … +3 more , Peterson JE, Hamadeh F, Graffeo CS
Immunol Res · 2026 Jan · PMID 41483370 · Publisher ↗
IHP is a rare inflammatory disorder characterized by dural thickening. Its nonspecific presentation often leads to diagnostic challenges and potential misdiagnosis as a neoplasm. Literature review and illustrative case e...
IHP is a rare inflammatory disorder characterized by dural thickening. Its nonspecific presentation often leads to diagnostic challenges and potential misdiagnosis as a neoplasm. Literature review and illustrative case example. PubMed search using terms related to IHP yielded 272 candidate citations, 50 of which met study criteria and were included. A 40-year-old woman presented with headache, dizziness, and blurred vision. Surgical intervention via right craniotomy was recommended due to diagnostic uncertainty, symptomatic mass effect, and the potential for a malignant diagnosis. A near-total resection of the mass and its dural base was performed given the involvement of the transverse-sigmoid sinuses; histopathology revealed dense fibrous tissue with chronic inflammatory cell infiltration. Immunohistochemistry was positive for CD3 and CD20, and negative for EMA, SSTR2, IgG, and IgG4, confirming the diagnosis of IHP. Review of the literature identified 117 patients presenting at a median age of 51 years with slight female predominance. Headache was the most common symptom (94%), followed by cranial nerve deficits (49%). MRI was used in all cases, with the tentorium being the most frequent site of involvement (48%). Treatment typically involved biopsy (47%), resection (11%), long-term steroids (56%), or steroid taper (44%). Radiographic recurrence was observed in 35%. Based on the experience from our case and supportive summative evidence from the literature, we developed a clinical decision-making schema to assist clinicians in recognizing and managing IHP. IHP remains a diagnostic challenge due to its rarity, nonspecific presentation, and potentially confounding radiographic features.
From immunosuppression to immune reprogramming: is triptolide a potential "immune reset" agent in autoimmune diseases?
Yu D, Lin H
Immunol Res · 2025 Dec · PMID 41455031 · Full text
Current biologics and small-molecule inhibitors for autoimmune diseases often provide symptomatic relief but fail to restore immune tolerance, necessitating lifelong treatment with associated risks. Triptolide, a natural...
Current biologics and small-molecule inhibitors for autoimmune diseases often provide symptomatic relief but fail to restore immune tolerance, necessitating lifelong treatment with associated risks. Triptolide, a natural compound from Tripterygium wilfordii Hook F, exhibits a unique capacity for immune reprogramming, simultaneously suppressing pathogenic immunity while enhancing regulatory functions, positioning it as a potential 'immune reset' agent. However, its clinical translation is plagued by a narrow therapeutic window due to mechanism-based toxicity, creating a critical challenge of decoupling efficacy from toxicity. This review moves beyond a descriptive cataloguing of triptolide derivatives to provide a critical appraisal of the field's progress in achieving this decoupling. We systematically evaluate the most promising candidates (e.g., LLDT-8, Minnelide, ZT01), not only examining their mechanisms but also analyzing why most stall in early development. By integrating mechanistic insights with clinical progress data, we dissect the structural determinants of toxicity and efficacy and propose a concrete future roadmap focused on rational drug design (e.g., novel targets like TAK1), targeted delivery systems, and biomarker-driven precision medicine to advance safe and effective triptolide-based therapies to the clinic.
Maternal RSV vaccine: a systematic review and meta-analysis of immunogenicity and perinatal safety.
Saad K, Alomari O, Dizdarogulları GE … +17 more , Mokresh ME, Hussein WM, Eyvazova H, Kaplan O, Ghahremanpour GK, Hamam M, Api M, Elgenidi A, Elhoufey A, Hassan AM, Temsah MH, Ahmad AR, Alnusayri A, Abdel-Sadek ZM, ElAshry A, Alhasan KA, Abo-Elela MGM
Immunol Res · 2025 Dec · PMID 41455011 · Publisher ↗
This systematic review and meta-analysis assess the immunogenicity and maternal-fetal safety profile of RSV prefusion F (RSVpreF) vaccination during pregnancy. PubMed, Scopus, Embase, Cochrane, and Web of Science databas...
This systematic review and meta-analysis assess the immunogenicity and maternal-fetal safety profile of RSV prefusion F (RSVpreF) vaccination during pregnancy. PubMed, Scopus, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Only randomized controlled trials (RCTs) evaluating the safety, efficacy, and immunogenicity of RSVpreF vaccination in pregnant women were included. Six RCTs, involving 17,212 participants, were analyzed. The vaccine significantly boosted maternal anti-RSV neutralizing antibody levels, with a standardized mean difference (SMD) of 1.40 for RSV-A and 1.11 for RSV-B, both with high statistical significance. Infants born to vaccinated mothers had a 49% reduced risk of RSV-associated lower respiratory tract illness within 180 days post-vaccination (OR = 0.51, 95% CI: 0.40-0.64). Preterm birth rates did not differ significantly between the vaccine and placebo groups (OR = 1.09, 95% CI: 0.87-1.37). The vaccine was not associated with increased risks of serious adverse events or perinatal complications. Maternal RSVpreF vaccination significantly elevates neutralizing antibody levels against RSV subtypes A and B without increasing the risk of serious adverse events or preterm delivery. These findings support the safety and immunogenicity of RSV vaccination in pregnant women, reinforcing its potential utility in protecting neonates against RSV-related morbidity.
Predictive value of serum lipid for kawasaki disease shock syndrome: a prospective study.
Wu P, Li B, Wu J … +9 more , Li Y, Ma F, Zhang N, Liu X, Hua Y, Zhou K, Wang C, Duan H, Shao S
Immunol Res · 2025 Dec · PMID 41428125 · Publisher ↗
Background Kawasaki disease shock syndrome (KDSS) is a severe form of Kawasaki disease (KD). The serum lipid has been proposed to be valuable in predicting shock syndrome in clinical circumstances; however, limited data...
Background Kawasaki disease shock syndrome (KDSS) is a severe form of Kawasaki disease (KD). The serum lipid has been proposed to be valuable in predicting shock syndrome in clinical circumstances; however, limited data is available in KDSS patients. Therefore, we prospectively evaluated the ability of serum lipid in predicting KDSS. Methods A total of 1009 KD patients aged 2 months to 139 months were enrolled in this prospective cohort study between June 2017 and April 2022. The demographic/clinical characteristics and laboratory data were compared between the patients with KDSS (KDSS group) and those without (KD group). Multivariate logistic regression analysis was utilized to determine the correlation between serum lipid and KDSS. Receiver operating characteristic (ROC) curve analysis was subsequently performed to assess the validity of serum lipids in predicting KDSS. Results Except for triglyceride (TG), almost all the levels of detected lipid profiles were significantly lower in the KDSS subjects compared to non-KDSS patients. In terms of KDSS prediction, the cut-off values of 2.845 mmol/L, 0.355 mmol/L, 1.405 mmol/L, 0.595 g/L, and 0.805 g/L for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo A) and apolipoprotein B (Apo B), yielded sensitivities of 80%, 68%, 64%, 76% and 88%, with specificities of 69%, 93%, 89%, 83% and 51%, respectively. Conclusions Lipid profiles were robustly dysregulated in KDSS patients. Noticeably, serum lipid was a complementary laboratory marker for KDSS prediction.
Pediatric selective IgM deficiency: clinical features and a preliminary risk index for immunoglobulin replacement therapy.
Ozdemir E, Karaselek MA, Guner SN … +2 more , Keles S, Reisli I
Immunol Res · 2025 Dec · PMID 41428115 · Publisher ↗
Selective immunoglobulin M deficiency (SIgMD) is a rare pediatric antibody defect with poorly defined thresholds for immunoglobulin replacement therapy (IgRT). We retrospectively reviewed 5,122 serum IgM measurements (20...
Selective immunoglobulin M deficiency (SIgMD) is a rare pediatric antibody defect with poorly defined thresholds for immunoglobulin replacement therapy (IgRT). We retrospectively reviewed 5,122 serum IgM measurements (2005–2024) and identified 21 children meeting SIgMD criteria (IgM < 20 mg/dL with normal IgG/IgA). Nine had isolated SIgMD, while 12 presented with comorbid conditions. Recurrent tonsillopharyngitis was more frequent in isolated cases, whereas low isohaemagglutinin titres and lymphopenia were confined to the comorbidity group. IgRT was initiated in 11 patients, predominantly those with comorbidities (75% vs. 22%). Firth-penalised logistic regression confirmed comorbidity as the only independent correlation of IgRT. An exploratory four-parameter framework (comorbidity, isohaemagglutinin titres, lymphopenia, baseline IgA) achieved good discrimination for predicting treatment need (AUC = 0.80, optimism-adjusted AUC = 0.80). These findings suggest that routine laboratory markers may help identify children at higher risk of requiring IgRT, but validation in larger multicentre cohorts is essential.
Somatic mosaicism of CYBB causing atypical CGD with inflammatory symptoms.
Kang Z, Qiu X, Ma Y … +1 more , Zhang L
Immunol Res · 2025 Dec · PMID 41410980 · Publisher ↗
Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI) characterized by a defective respiratory burst in phagocytes and defective clearance of phagocytosed microorganisms. CGD is caused by a defect...
Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI) characterized by a defective respiratory burst in phagocytes and defective clearance of phagocytosed microorganisms. CGD is caused by a defect of the enzyme NADPH oxidase, resulting in severe and life-threatening infections in affected children. The genetically heterogeneous X-linked recessive form of CGD (XL-CGD) is caused by mutations in the CYBB gene. XL-CGD is typically diagnosed early in life, usually before the age of 3 years. The present report describes a boy aged 9 years and 11 months who presented with oral ulcers, cutaneous lesions, and uveitis. Whole-exome sequencing (WES) detected a mosaic, pathogenic nonsense variant (p.Arg157X) in CYBB. This pathogenic variant was present in ~ 60% of peripheral leukocytes in this patient, a percentage sufficient to result in defective production of reactive oxygen species (ROS), but not life-threatening infections, including BCG lymphadenitis following BCG vaccination. This study describes a somatic mosaicism mutation in the CYBB gene that can cause atypical CGD with inflammatory symptoms.
Myeloid inflammation thresholds stratify mortality risk in early-stage cardiovascular-kidney-metabolic syndrome: MLR-driven findings from NHANES.
Qu Y, Wang L, Liu L … +1 more , Sun Y
Immunol Res · 2025 Dec · PMID 41410725 · Full text
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a major public health concern associated with increased mortality. Inflammation plays a critical role in CKM progression and outcomes. This study investigates...
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a major public health concern associated with increased mortality. Inflammation plays a critical role in CKM progression and outcomes. This study investigates the relationship between inflammatory indices and mortality risk in CKM patients. METHODS: A comprehensive analysis of data from 26,265 participants in the National Health and Nutrition Examination Survey (NHANES) database (2007-2016) with CKM syndrome stages 0-4 was conducted. The primary outcomes of the study were all-cause and cardiovascular mortality. The inflammatory indices encompassed the systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and neutrophil-to-albumin ratio (NAR). Multivariable Cox models, adjusted for demographic and clinical confounders, were employed to examine nonlinearity, alongside restricted cubic splines and threshold analyses. The present study sought to compare the prognostic accuracy of the time-dependent ROC (Receiver Operating Characteristic) at 93 months. RESULTS: During a median follow-up of 93.4 months, 2,292 subjects experienced all-cause mortality and 701 experienced cardiovascular deaths. In the adjusted models, elevated SIRI (all-cause HR 1.11, 95% CI 1.06-1.15; cardiovascular HR 1.18, 1.10-1.27), NLR (all-cause HR 1.08, 1.05-1.12; cardiovascular HR 1.11, 1.05-1.17) and MLR (all-cause HR 2.27, 1.71-3.01; cardiovascular HR 3.37, 2.09-5.44) were independently associated with mortality (all p < 0.0001). Dose-response analyses revealed nonlinear J-shaped relationships: MLR showed marked risk above 0.19 (HR 2.59), NLR risk was greatest below 3 (HR 1.14), and SIRI thresholds differed for all-cause (> 1.74, HR 1.09) versus cardiovascular (> 0.38, HR 1.17) outcomes. At 93 months, MLR demonstrated the highest discriminatory ability (AUC 0.630; C-index 0.667; p < 0.001), outperforming SIRI (AUC 0.611) and NLR (AUC 0.602). PLR, AISI, SII and NAR showed limited predictive value due to imbalanced sensitivity-specificity. The impact of age and the early stages of CKD on the modification of associations was investigated. CONCLUSION: Systemic inflammatory indices demonstrated nonlinear, J-shaped associations with mortality in CKM syndrome, with the MLR showing the strongest association across disease trajectories. MLR, NLR, and SIRI were identified as potential risk indicators, with stronger associations observed in younger patients and those with early-stage CKM syndrome. HIGHLIGHTS: Systemic inflammatory markers (SIRI, NLR, MLR) were significantly associated with increased mortality risk in CKM syndrome. Most inflammation indices exhibited nonlinear, J-shaped associations with mortality. Nonlinear threshold analyses identified specific risk inflection points for SIRI, NLR, and MLR. These associations were stronger in younger patients (≤ 60 years) and those with early CKM stages (1-2).
Efficacy and safety of natural killer cell therapy for the treatment of advanced non-small cell lung cancer: A meta-analysis and systematic review.
Li Z, Wang X, Chen S … +4 more , Zhang P, Wang X, Ni X, Mou C
Immunol Res · 2025 Dec · PMID 41350490 · Full text
To evaluate the efficacy and safety of natural killer (NK) cell therapy for the treatment of advanced non-small cell lung cancer (NSCLC). Relevant studies on NK cell therapy for advanced NSCLC were collected from PubMed,...
To evaluate the efficacy and safety of natural killer (NK) cell therapy for the treatment of advanced non-small cell lung cancer (NSCLC). Relevant studies on NK cell therapy for advanced NSCLC were collected from PubMed, Scopus, Embase and the Cochrane Library up to August, 2024. Two reviewers independently screened the articles and retrieved the data using the Cochrane risk assessment tool. Meta-analysis was conducted with R (version 4.3.1). A total of nine trials were analyzed, including five phase 2 randomized controlled and four phase 1 studies. All were medium to high quality but exhibited high performance and attrition biases. NK cell treatment doses ranged from 1×10 to 4×10 cells for 2 or 3 cycles. In total, 324 patients with advanced NSCLC were included, comprising 199 who received NK cell therapy and 125 controls, all previously treated with platinum-based regimens. Meta-analysis demonstrated comparable disease control (OR = 2.68; 95% CI: 1.53-4.71) and 1-year survival (OR = 2.54; 95% CI: 1.28-5.02) between groups, with similar adverse events rates (OR = 1.37; 95% CI: 0.35-5.26). Subgroup analyses revealed no significant differences in efficacy. There was considerable heterogeneity among studies (I² = 0%-92.5%). Over 39 trials were registered, with only 12 marked as completed and none of the others released the outcome data. Current evidence suggests that NK cell therapy, either alone or in combination, may achieve disease control, survival outcomes and safety profiles that were comparable to existing treatments for advanced NSCLC. These findings remain exploratory and should be confirmed in larger, well-designed trials.
Macrophage-derived exosomes in autoimmune diseases: mechanistic insights and therapeutic implications.
Zheng A, Liu H, Yin G … +1 more , Xie Q
Immunol Res · 2025 Nov · PMID 41307794 · Publisher ↗
Autoimmune diseases are characterized by an aberrant immune response that targets the body's own tissues, resulting in chronic inflammation and organ damage. Recently, macrophage-derived exosomes (M-Exos), nanoscale vesi...
Autoimmune diseases are characterized by an aberrant immune response that targets the body's own tissues, resulting in chronic inflammation and organ damage. Recently, macrophage-derived exosomes (M-Exos), nanoscale vesicles that transport bioactive molecules, have gained recognition as significant mediators of immune regulation and disease progression. These exosomes possess the unique ability to traverse physiological barriers while reflecting the functional states of their originating cells. Consequently, M-Exos exert influence over various immune cell populations, including macrophages, T cells, B cells, and dendritic cells. The distinct profiles of M1- versus M2-derived exosomes illuminate their differing roles in immune activation and resolution. This review compiles current evidence regarding the involvement of M-Exos in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, emphasizing their potential as both biomarkers and therapeutic agents. By integrating recent advancements and identifying outstanding questions, we propose a framework for employing M-Exos in diagnosis, prognosis, and personalized treatment strategies.
The osteoclast blind spot and other unresolved mechanisms in the exosomal theory of tuberculosis-induced osteoporosis.
Qi L, Gu Q, Chen B … +2 more , Yang D, Li D
Immunol Res · 2025 Nov · PMID 41296095 · Publisher ↗
The recent study by Zhao et al. ( Inflamm Res. 2025) proposed a novel paradigm in which exosomal miR-125b-5p from Mycobacterium tuberculosis-infected macrophages impairs osteoblast function by targeting IGF2, thereby lin...
The recent study by Zhao et al. ( Inflamm Res. 2025) proposed a novel paradigm in which exosomal miR-125b-5p from Mycobacterium tuberculosis-infected macrophages impairs osteoblast function by targeting IGF2, thereby linking pulmonary infection to systemic osteoporosis. While this work provides a valuable mechanistic insight, our letter offers a critical appraisal to contextualize its findings and highlight pivotal unanswered questions. We posit that the proposed pathway, though compelling, requires further validation to establish direct causality in vivo, independent of the well-established role of systemic inflammatory cytokines. Furthermore, the model remains incomplete as it overlooks the potential synergistic impact of the exosomal cargo on osteoclast activation, thereby presenting only a partial view of the bone remodeling unit. Substantive questions regarding the specificity of miR-125b-5p as the sole effector, the biodistribution mechanisms of these exosomes, and their pathogen-specific nature also warrant urgent investigation. Addressing these gaps is not merely academic but is crucial for assessing the true therapeutic potential of targeting this exosomal axis in clinical practice.
Prevalence, incidence, and mortality of autoimmune diseases among adolescents and young adults in Mexico: an analysis based on the global burden of disease study 2021.
Mendoza-Pinto C, Munguía-Realpozo P, Etchegaray-Morales I … +7 more , Solis-Mendoza F, Gálvez-Romero JL, Ramírez-Lara E, González MAT, Juárez BMS, Flores MAG, Méndez-Martínez S
Immunol Res · 2025 Nov · PMID 41276722 · Publisher ↗
This nationwide analysis quantified the contemporary and future burden of six autoimmune diseases (ADs)-rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM...
This nationwide analysis quantified the contemporary and future burden of six autoimmune diseases (ADs)-rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), asthma, and psoriasis-among Mexican adolescents and young adults (AYAs, 10-24 years) using the Global Burden of Disease 2021 database. Age-standardised prevalence (ASPR), incidence (ASIR), and mortality (ASMR) rates for 2021 were calculated by direct standardisation to the GBD world population; 1990-2021 temporal patterns were explored through Joinpoint regression to derive average annual percentage change, and Box-Jenkins ARIMA models projected trends up to 2035, incorporating diagnostic-capacity covariates. In 2021, RA had the greatest burden (ASPR 45.7/100,000; ASIR 9.1), with a striking female predominance and north-south variability. Although IBD remained infrequent, its mortality rose in states where colonoscopy access expanded, suggesting detection bias yet underscoring rising severity. MS prevalence and incidence climbed steadily, particularly among young women in urbanised regions. T1DM maintained the highest absolute caseload and incidence but showed slowly declining rates; nevertheless, ASMR inched upward, reflecting suboptimal metabolic control. Asthma, while still the most prevalent AD, exhibited a modest downward trajectory, whereas psoriasis incidence was stable, yet prevalence remained substantial, signalling chronic disease accumulation. Forecasts predict moderate growth in RA and MS cases, relative plateauing of IBD, asthma, and psoriasis, and continued contraction of T1DM incidence with a slight mortality uptick. Persistent geographic and sex-related inequities highlight the necessity for region-specific prevention strategies, earlier immune-modulating therapy, and equitable access to specialised care to mitigate the projected AD burden in Mexican AYAs.
RNA-based cancer vaccines: mechanisms, clinical progress, and translational challenges.
Al-Kabariti AY, Kadhim MA, Mousa HM … +5 more , Jyothi SR, Nayak PP, Janney JB, Singh G, Chauhan AS
Immunol Res · 2025 Nov · PMID 41264102 · Publisher ↗
Recent advancements in vaccine technology have led to the development of RNA-based vaccines, including mRNA, circular RNA, and self-amplifying mRNA, which have emerged as a promising platform for tumor prevention and tre...
Recent advancements in vaccine technology have led to the development of RNA-based vaccines, including mRNA, circular RNA, and self-amplifying mRNA, which have emerged as a promising platform for tumor prevention and treatment. In comparison with conventional antitumor vaccines, such as whole cell, peptide, and DNA vaccines, RNA vaccines possess several advantageous characteristics. They have the capacity to encode multiple antigens, induce robust immune responses, and can be developed more expeditiously. Additionally, RNA vaccines have the potential for scalable manufacturing with acceptable safety profiles in cancer patients. Preliminary investigations, conducted both in preclinical and clinical settings, have yielded encouraging outcomes for RNA vaccines in the context of diverse tumor types. This review delineates the types, advances, and applications of RNA vaccines in antitumor therapy, as well as the challenges associated with their use. Finally, it introduces future technological directions for improving these current vaccine platforms for a wide range of therapeutic uses.
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