Humoral immunity depends upon long-lived, antibody-secreting plasma cells and memory B cells (MBCs). MBCs exhibit significant phenotypic and functional heterogeneity shaped by interactions with CD4+ T cells. It is currently unclear how specific CD4+ T cell interactions with B cells influence specific MBC subset generation. We used genetic ablation and antibody depletion to dissect key CD4+ T cell/B cell receptor-ligand pair interactions to define critical signals that govern the development of specific MBC populations. While it has previously been suggested that CD73+CD80+ MBCs are derived from the germinal center (GC), we show that highly functional CD73+CD80+ IgM+ MBCs differentiate in a BCL6- and CD4+ T cell-dependent but GC Tfh-independent manner. BCL6 upregulation, in the presence or absence of a GC, can therefore serve as a predictor of long-lived, functional MBCs.

Clinico-pathological and immunohistochemical profile of plasma cell rich variants of chronic cholecystitis.

Effects of crackers enriched with polyunsaturated fatty acids with benefits for improving metabolic parameters: A double-blind randomized controlled trial in subjects with overweight.

Critical roles of CD4-1+ T cells and their secreted IL-21 in vaccine-induced humoral immunity in grass carp.

B cell development and longevity of IgE plasma cells.

Circulating tumor cells (CTCs) have emerged as a key component of liquid biopsy in multiple myeloma (MM), reflecting the ability of malignant plasma cells to escape the bone marrow (BM) niche, disseminate systemically, and contribute to disease progression. Their detection in peripheral blood is now feasible across the disease spectrum, from MGUS and smoldering myeloma to solitary plasmacytoma, symptomatic MM, and plasma cell leukemia, providing a dynamic window into tumor biology. Technological advances, including high-sensitivity flow cytometry and next-generation single-cell sequencing, have enabled accurate enumeration and molecular interrogation of CTC. Beyond their biological significance, CTC quantification has consistently demonstrated independent prognostic value at diagnosis, with even low levels predicting inferior survival outcomes. Recent proof-of-concept studies, such as MinimuMM-seq and SWIFT-seq, established that genomic and transcriptomic profiling of CTC can recapitulate canonical myeloma lesions, reveal clonal heterogeneity and track evolutionary dynamics under therapy. Importantly, persistent or reemergent CTC after are occasionally observed and, when present, may signal relapse, particularly, in patients with BM-MRD positivity, highlighting their potential as complementary biomarkers alongside established BM MRD assessment. Although methodological challenges remain-particularly, standardization, sensitivity, and integration into clinical workflows-CTC analysis holds the promise of transforming from a surrogate biomarker to a clinically actionable tool, advancing precision medicine in MM.

Multiple myeloma is an incurable plasma cell malignancy. Its prognosis improved with the introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, but outcomes for triple-class-exposed (TCE) myeloma remained poor. New therapeutic options including CAR-T cell therapy and bispecific antibodies have now further improved prognosis, even in TCE myeloma. While true cure remains challenging, functional cure, defined as long-term disease control through a favorable immune environment suppressing minimal residual disease (MRD), is currently considered a realistic therapeutic goal.

Plasma cell myeloma is a heterogeneous hematologic malignancy characterized by clonal expansion of plasma cells. While RAS-MAPK pathway mutations are known high-risk features, the clinical relevance of STAT3/STAT5 mutations remains unclear. We analyzed 16 myeloma patients with STAT3/STAT5 mutations identified by next-generation sequencing (9 STAT3, 5 STAT5A, 2 STAT5B) and compared them with 32 mutation-negative controls. STAT3/STAT5 mutations were present at initial diagnosis in all eight patients with available initial sequencing data, suggesting these are early events in pathogenesis. STAT3/STAT5 mutations were the sole mutations in five patients, while 10 had co-mutations, most frequently in KRAS/NRAS (n = 5) and TP53 (n = 3). In co-mutated cases, STAT3/STAT5 represented the dominant clone in 4 and co-dominant in 6. All mutations were missense, with 63% involving the SH2 domain. Compared with controls, STAT3/STAT5-mutated patients had higher serum lactate dehydrogenase levels, higher incidence of IgA paraprotein, higher R-ISS stage, more complex karyotype, and frequent CKS1B gain/amplification. Overall survival was significantly shorter in patients with STAT3/STAT5 mutations (median 42 vs. 72 months, p < 0.0001). STAT3/STAT5 mutations are early, dominant, and potentially pathogenic events in plasma cell myeloma. Their association with adverse clinical features and inferior survival supports their routine assessment and potential therapeutic targeting.

Dual biomarkers ALOX5AP and INPP4A are associated with lipid metabolism and neutrophil extracellular traps in periodontitis: A bioinformatics and clinical validation study.

The host immune determinants that distinguish protective from life-threatening responses to influenza are poorly understood. Identifying drivers of immunopathology in the human lung is critical for developing potential therapies. To define the cellular and molecular immune landscape of the lung in mild vs severe influenza and to identify key cellular states and pathways associated with disease severity. We generated a large-scale single-cell atlas by sequencing more than 520 000 cells from the bronchoalveolar lavage fluid of 88 nonimmunocompromised adult individuals with mild or severe influenza A and healthy controls. Key findings were validated by flow cytometry and protein quantification, and machine-learning models were used to identify predictive signatures. Severe influenza was characterized by profound pulmonary lymphopenia and a massive influx of functionally dysregulated neutrophils. The infiltrating neutrophils were primed for extracellular trap formation, driving a cytokine storm via the S100A8/A9/A12-TLR4 and CXCL8-CXCR1/2 axes. This pathology coincided with the depletion and functional impairment of resident alveolar macrophages and an expansion of pro-inflammatory, monocyte-derived macrophages that amplified neutrophil recruitment. Lymphopenia in severe disease arose from synergistic cell-death programs, while remaining lymphocytes exhibited a dysfunctional state of concurrent exhaustion and hypercytotoxicity. Mild influenza featured a coordinated adaptive immune response, distinguished by an enrichment of T follicular helper cells and plasma cells. Machine-learning models identified robust cellular and transcriptional signatures predictive of disease severity. Our atlas defines the divergent immune trajectories in influenza, revealing specific cellular states and pathways that drive immunopathology and provide novel targets for host-directed therapies.

The purpose of this study was to explore the composition and function of immune cell subsets at the single-cell level in the thymus and peripheral blood of patients with myasthenia gravis (MG). A total of 9701 and 23 846 cells, respectively, originated from the peripheral blood and thymus samples of two MG patients, and 6930 cells from the peripheral blood of two gender- and age-matched healthy controls (HCs) were selected for single-cell RNA-sequencing. Uniform manifold approximation and projection (UMAP), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Monocle3, and Velcyto were performed to analyze the composition, molecular and functional properties, and developmental trajectory of immune cell subsets. Four major cell populations of T cells, B cells, myeloid cells, and natural killer cells were identified, as well as their 15 cell subpopulations. An absolute predominance of T cells was found in the thymus and peripheral blood of MG patients, and the proportions of memory B cells in both plasma and thymus showed an increasing trend while the number of naïve B cells demonstrated a decreasing trend in MG patients compared with HCs. Besides, the monocytes in the peripheral blood of MG patients had the strongest interactions with other cells. Furthermore, CXCL, GAS, and CD30 signaling pathways were more enriched within MG peripheral blood. Our research clarifies the cellular heterogeneity in the pathogenesis of MG and characterizes the immune microenvironment of thymic tissues in MG patients.

Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with a risk of progression to multiple myeloma. Metabolic syndrome (MetS) is implicated in cancer development, yet its association with MGUS remains unclear. We examined MetS as a risk factor for MGUS in a large Korean cohort. In a retrospective cohort study using the National Health Information Database, we analyzed 4,453,504 adults undergoing health checkups in 2012, followed through up to 2022. MetS was defined by NCEP-ATP III criteria. Over a median 9.3-year follow-up, 1,241 MGUS cases were identified. MetS was associated with a 28% increased MGUS risk (hazard ratio [HR]=1.28; 95% confidence interval [CI]: 1.14- 1.44). Risk escalated with more MetS components, peaking at 76% for five components (HR=1.76; 95% CI: 1.35-2.30). Low high-density lipoprotein cholesterol, hypertension, and central obesity were key risk factors, with higher risks in males and younger adults (range, 20-39 years). Longitudinal analysis showed MetS onset (HR=1.25; 95% CI: 1.06-1.47) or persistence (HR=1.25; 95% CI: 1.06-1.48) increased MGUS risk compared to persistent MetS absence, whereas MetS resolution showed no significant risk increase over persistent MetS absence. MetS increases MGUS risk, particularly in males and younger individuals. Resolving MetS may mitigate MGUS risk, supporting targeted metabolic interventions.

Encephalopathy is a heterogeneous clinical syndrome with numerous neurological and systemic etiologies. We report the case of a 67-year-old man, a chronic ethanol consumer, admitted with a one-week history of confusional syndrome. Initial laboratory tests revealed severe hypercalcemia, acute kidney injury, mild anemia, and hyperproteinemia. Serum ammonia levels were within normal limits, reducing the likelihood of hepatic encephalopathy despite the patient's chronic ethanol use. Cerebral imaging excluded acute cerebrovascular events, while abdominal ultrasound demonstrated splenomegaly and normal-sized kidneys. Serum protein electrophoresis and immunofixation identified a monoclonal IgG-kappa component, strongly suggestive of multiple myeloma. The patient's neurocognitive symptoms improved rapidly following systemic corticosteroid therapy and fluid-electrolyte rebalancing, confirming hypercalcemia as the primary mechanism of encephalopathy. Hypercalcemic encephalopathy as an initial manifestation of multiple myeloma is exceedingly rare. This case highlights the diagnostic complexity in elderly patients with multiple potential contributors to altered mental status, including chronic ethanol exposure and renal dysfunction. The presence of normal renal dimensions, unexplained hypercalcemia, and a monoclonal component should prompt evaluation for plasma cell malignancy. Early recognition of hypercalcemia-induced encephalopathy and prompt investigation for underlying hematologic malignancy are essential to prevent irreversible organ damage and to ensure timely initiation of specific therapy.

To further understand the mechanism of action of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with systemic lupus erythematosus (SLE) in the phase 2 PAISLEY SLE trial. RNA sequencing (RNA-seq) was performed on samples collected from baseline to week 32 in 363 patients and 56 healthy volunteers. Pharmacodynamics of differentially expressed genes (DEGs) were analysed with linear mixed-effects models using the statistical software package DREAM (differential expression for repeated measures). Single-sample gene set enrichment analysis (ssGSEA) was performed using MSigDB Hallmark and BloodGen3 gene modules. The xCell R package was used to digitally portray the blood cellular heterogeneity landscape. At baseline, 527 DEGs were identified in patients with SLE vs healthy volunteers (log2 fold change >1; adjusted P < .05). Deucravacitinib modulated up to 2529 genes and SLE-relevant gene sets, including interferon-regulated genes. ssGSEA showed that plasma cell gene sets decreased and myeloid cell gene sets reverted towards normal levels with deucravacitinib; xCell deconvolution revealed significant enrichment of dendritic cell populations with deucravacitinib vs placebo. At baseline, regulatory T-cell gene sets were increased in patients with SLE vs healthy volunteers and further increased with deucravacitinib. There were some variable, dose-dependent increases in naïve and memory B lymphocytes. Whole blood transcriptome profiling via RNA-seq revealed both expected and novel gene expression changes with deucravacitinib across multiple pathogenic pathways. These data demonstrate successful targeting of pathophysiologic immune mechanisms that should be validated in future studies and support continued evaluation of deucravacitinib in the phase 3 POETYK SLE trials.

To explore the correlation between serum and glucocorticoid inducible kinase-1 (SGK1) expression levels and the multiple myeloma (MM) progression in patients after autologous stem cell transplantation (ASCT).A total of 100 MM patients who received ASCT in the Hematology Department of our hospital during January 2020 to December 2022 were selected as the research subjects. The mRNA level of SGK1 was detected by RT-PCR. Taking the median relative expression level of SGK1 mRNA (2.15) as the critical value, these subjects were divided into SGK1 high expression group (SGK1 mRNA ≥ 2.15, n = 43) and SGK1 low expression group (SGK1 mRNA < 2.15, n = 57). The expression level of SGK1 was detected by IHC. The correlation was analyzed by Spearman correlation coefficient. The survival curve drawn through Kaplan-Meier method was further verified using Log-rank test. Cox proportional hazard regression model was used for multivariate analysis to screen independent risk factors. The receiver's working characteristic (ROC) curve was drawn to evaluate the predictive value.The H-Score was significantly higher in the SGK1 high expression group (8.52 ± 2.13) than the low expression group (3.27 ± 1.68) (t = 11.240, P < 0.001). After induction therapy, SGK1 high expression group had much lower proportion of achieving complete remission (CR), and markedly higher serum levels of β2-MG and LDH than SGK1 low expression group (P < 0.05). The expression of SGK1 in patients with partial remission (PR) was significantly higher than those with CR and very good partial remission (VGPR) (P < 0.01). Median TTP, median PFS and median OS were significantly lower in SGK1 high expression group than the SGK1 low expression group (Log-rank P < 0.01). Three months after transplantation, the positive rate of Minimal residual disease (MRD) was 48.84% (21/43) in SGK1 high expression group and 22.81% (13/57) in SGK1 low expression group (P < 0.01). The expression level of SGK1 was positively correlated with serum β2-MG (r = 0.452, P < 0.01), LDH (r = 0.388, P < 0.01), the proportion of plasma cells in bone marrow (r = 0.321, P < 0.01), and pre-transplant remission status (CR = 1, VGPR = 2, PR = 3; r = 0.413, P < 0.01), but negatively correlated with PFS (r= - 0.527, P < 0.01) and OS (r= - 0.482, P < 0.01). High SGK1 expression, serum β2-MG, and positive LDH and MRD were independent risk factors (P < 0.05). The ROC curve analysis of predicting disease progression after transplantation based on the relative expression level of SGK1 mRNA showed the area under the curve (AUC) of 0.883 (95% CI: 0.785-0.934), an optimal cutoff value of 2.18, a sensitivity of 94.32%, and a specificity of 73.63%.High expression of SGK1 was an independent risk factor for disease progression after ASCT in MM patients, which was closely related to the short survival time and high MRD positive rate. The expression level of SGK1 had a certain predictive effect on the disease progression after transplantation.

Non-secretory multiple myeloma (NSMM) is a rare variant of multiple myeloma with an incidence rate of 1.0% to 5.0% in all MM cases. It is characterized by symptomatic myeloma in the absence of detectable monoclonal immunoglobulin levels on serum or urine electrophoresis. It often poses a diagnostic dilemma due to its need for more evident features. We report such a non-secretory plasma cell myeloma that manifested as nonspecific back pain and a lytic lesion in the lumbar spine MRI. Confirming an accurate diagnosis early was difficult since no monoclonal immunoglobulin was detected on serum or urine electrophoresis. However, based on the bone marrow study, he was eventually diagnosed as having non-secretory multiple myeloma. He is currently being treated with chemotherapy and has already shown improvement. This case report emphasizes the need for early bone marrow studies and light chain assays in diagnosing non-secretory forms of multiple myeloma if the presentation is indicative. This will help to avoid diagnostic delays, which can finally lead to favorable outcomes if properly addressed.

Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Targeting B-cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T-cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient-reported outcomes, and comparative positioning within the evolving BCMA-directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low-grade cytokine release syndrome and limited neurotoxicity when administered with step-up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA-targeted therapies and feasibility in selected high-risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long-term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real-world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.

Naive B cells diversify via clonal expansion, immunoglobulin isotype switching, phenotypic variation and somatic hypermutation (SHM). Diversity in antigenic targets, functional classes and the production kinetics of antibodies affects immunity to malaria. Here we show that individual clones diversify over time during Plasmodium infection. During the first week, amid widespread bystander activation, isotype switching initiates soon after Myc upregulation and overlaps with clonal expansion, resulting in isotype variegation among clones. During the second week, expanded clones seeding germinal centers (GC) bifurcate into extrafollicular plasmablasts, exhibit isotype variegation and initiate SHM, indicating substantial intraclonal diversification. Over the following month, GC clones exhibit SHM at approximately four mutations per week. Antimalarial intervention does not impede SHM, instead exerting quantitative limits on GC size, plasma cell emergence, circulating antibody levels and protection against reinfection. Finally, contemporaneous B cell development relocates from bone marrow to spleen. Thus, multiple temporally overlapping mechanisms combine in vivo to diversify and safeguard humoral immune responses.

A 77-year-old woman with newly diagnosed immunoglobulin (Ig)G-κ multiple myeloma presented with a massive cranial paraskeletal (PS) lesion (84 × 59 × 62mm) compressing the occipital lobe. Fluorescence in situ hybridization of bone marrow aspirate revealed 1q21 gain and 17p deletion. Induction therapy with isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) was initiated to avoid emergent local intervention. The response was rapid; head computed tomography on day 28 showed an approximately 80% reduction in bidimensional measurements, with near-complete radiologic resolution by the end of the second cycle. After the third cycle, elective reconstructive cranioplasty was performed. Although a pretreatment biopsy was not feasible, the resected tissue showed no detectable plasma cells. Measurable residual disease in the bone marrow was negative (< 10-5) after the fourth cycle. Exploratory longitudinal flow cytometry of the peripheral blood revealed baseline expansion of CD8-positive terminally differentiated effector memory re-expressing CD45RA (TEMRA) cells and persistent TEMRA subset dominance after the fourth cycle. This case suggests that upfront anti-CD38 antibody-containing quadruplet therapy can enable deferral of urgent local intervention through rapid cytoreduction in select patients with bulky cranial PS involvement, even in older adults with high-risk cytogenetic features and compromised immune profiles.