Clinical Immunology : the Official Journal of the Clinical Immunology Society

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the dysregulation of B cell subpopulation and function. Recent studies have suggested a potential role of ferroptosis, an iron-dependent form of regulated cell death, in the pathogenesis of SLE. Here, we demonstrate that B-cell ferroptosis occurs both in lupus patients and MRL/lpr mice. Treatment with liproxstatin-1, a potent ferroptosis inhibitor, could reduce autoantibody production, improve renal damage, and alleviate lupus symptoms in vivo...

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes. METHODS: We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH...

The regulatory effect of DNA methylation on the pathogenesis of acne vulgaris is completely unknown. Herein we analyzed the DNA methylation profile in skin samples of acne vulgaris and further integrated it with gene expression profiles and single-cell RNA-sequencing data. Finally, 31,134 differentially methylated sites and 770 differentially methylated and expressed genes (DMEGs) were identified. The multi-omics analysis suggested the importance of DNA methylation in inflammation and immunity in acne. And DMEGs were verified in an external dataset and were closely related to early inflammatory acne...

The combination of antiangiogenic agents and immune checkpoint inhibitors is more efficient than monotherapy in the management of hepatocellular carcinoma (HCC). Lenvatinib plus anti-PD1 antibodies have become the mainstay in HCC treatment. However, more than half the patients with HCC are non-responsive, and the mechanisms underlying drug resistance are unknown. To address this issue, we performed single-cell sequencing on samples from six HCC patients, aiming to explore cellular signals and molecular pathways related to the effect of lenvatinib plus anti-PD1 antibody treatment...

BACKGROUND: In our previous study, we found for the first time that temozolomide (TMZ), the first-line chemotherapeutic agent for glioblastoma (GBM), can generate a large amount of reactive oxygen species (ROS) under ultrasound irradiation. Sonodynamic therapy (SDT) using TMZ as the sonosensitizer produced more potent antitumor effects than TMZ alone. Here, we further evaluate the effects of TMZ-based SDT on subcellular structures and investigate the immunogenic cell death (ICD)-inducing capability of TMZ-based SDT...

Psoriasis is a chronic inflammatory skin disease, thought to be predominantly mediated by TH 17 cells. Significance of other inflammatory pathways and the innate immune system is not well understood and the spatial heterogeneity of inflammation in the skin has largely been overlooked. Our aim was to create a comprehensive map of skin inflammation in psoriasis, exploring the tissue patterning of inflammation. In situ whole transcriptome sequencing (spatial sequencing) was performed on lesional psoriatic skin in four patients with moderate-to-severe disease to quantify all expressed genes within a tissue section...

Infections with non-typhoidal Salmonella sp. have been documented in children with chronic granulomatous disease (CGD), but the prevalence of salmonella infection in children with CGD in underdeveloped countries is unknown. We assessed the clinical profiles of CGD patients diagnosed at our tertiary care centre in north India and had Salmonella sp.infections. We found three patients with Salmonella sp. bloodstream infections (2-proven, 1-probable) among the 99 CGD patients. After receiving cotrimoxazole prophylaxis following a CGD diagnosis, we noted that none of our patients experienced non-typhoidal salmonella infection...

No abstract text is available yet for this article.

Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding...

RATIONALE: A persistent autoimmune and inflammatory response plays a critical role in the progression of atherosclerosis. The transcription factor forkhead box P3 (Foxp3)+ CD4+ regulatory T cells (Foxp3+ Tregs) attenuate atherosclerosis. Latency-associated peptide (LAP)+ CD4+ T cells are a new class of Tregs whose role in atherosclerosis is unknown. OBJECTIVE: To investigate the function of CD4+ LAP+ Tregs in inhibiting inflammation and preventing atherosclerosis...

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T-cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T-cell immunity after thymus transplantation...

Psoriasis is a chronic recurrent skin disease, with excessive proliferation of keratinocytes. Recent studies indicated the pathogenic roles of circular RNA (circRNA) in psoriasis. Here, we screened the circRNA profiles from five psoriatic skin lesions and five normal skin tissues by circRNA sequencing and identified 1118 differentially expressed circRNAs (DECs) between psoriatic and normal groups. Among these DECs, high abundant circARNTL2 has been proven upregulated in psoriatic skin lesions by RT-qPCR assay...

Vitiligo is the most common disorder of depigmentation, which is caused by multiple factors like metabolic abnormality, oxidative stress and the disorders of immune. In recent years, several studies have used untargeted metabolomics to analyze differential metabolites in patients with vitiligo, however, the subjects in these studies were all in plain area. In our study, multivariate analysis indicated a distinct separation between the healthy subjects from plateau and plain areas in electrospray positive and negative ions modes, respectively...

Systemic autoimmune diseases are characterized by increased production of type I interferon (IFN-1) and upregulation of IFN-1-inducible genes, suggesting an important role of the IFN-1 pathway in their pathogenesis. Recent studies have demonstrated increased IFN-1 expression in both primary and secondary antiphospholipid syndrome (APS), along with increased toll-like receptor type 9 activity and plasmacytoid dendritic cell function. The increasing knowledge of the association between IFN-1 and APS pathology may provide a rationale for conducting clinical trials to assess the efficacy of IFN-1-targeting drugs in reducing APS-related complications...

PURPOSE: There are currently more than 480 primary immune deficiency (PID) diseases and about 7000 rare diseases that together afflict around 1 in every 17 humans. Computational aids based on data mining and machine learning might facilitate the diagnostic task by extracting rules from large datasets and making predictions when faced with new problem cases. In a proof-of-concept data mining study, we aimed to predict PID diagnoses using a supervised machine learning algorithm based on classification tree boosting...

Meta-analyses confirm a link between persistent human cytomegalovirus (HCMV) infections and cardiovascular disease, but the mechanisms are unclear. We assess whether proportions of T-cell populations are reliable predictors of subclinical atherosclerosis and/or reflect the burden of HCMV in healthy adults and renal transplant recipients (RTR). Samples were collected from healthy adults and RTR at baseline (T0) and after 32 (24-40) months (T1). Left carotid intima media thickness (cIMT) and proportions of T-cells expressing CD57, LIR-1 or the TEMRA phenotype increased in healthy adults and RTR...

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24)...

The advent of next-generation sequencing (NGS) technologies has greatly expanded our understanding of both the clinical spectra and genetic landscape of inborn errors of immunity (IEIs). Endogamous populations may be enriched for unique, ancestry-specific disease-causing variants, a consideration that significantly impacts molecular testing and analysis strategies. Herein, we report on the application of a 2-step NGS-based testing approach beginning with targeted gene panels (TGPs) tailored to specific IEI subtypes and reflexing to whole exome sequencing (WES) if negative for Northwest Algerian patients with suspected IEIs...

Peripheral blood monocytes propagate inflammation in systemic lupus erythematosus (SLE). Three major populations of monocytes have been recognized namely classical (CM), intermediate (IM) and non-classical monocytes (NCM). Herein, we performed a comprehensive transcriptomic, proteomic and functional characterization of the three peripheral monocytic subsets from active SLE patients and healthy individuals. Our data demonstrate extensive molecular disruptions in circulating SLE NCM, characterized by enhanced inflammatory features such as deregulated DNA repair, cell cycle and heightened IFN signaling combined with differentiation and developmental cues...

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls...