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Cell-Impermeable Buffering Fluorogenic Probes for Live-Cell Super-Resolution Imaging of Plasma Membrane Morphology Dynamics.

Super-resolution fluorescence imaging has emerged as a potent tool for investigating the nanoscale structure and function of the plasma membrane (PM). Nevertheless, the challenge persists in achieving super-resolution imaging of PM dynamics due to limitations in probe photostability and issues with cell internalization staining. Herein, we report assembly-mediated buffering fluorogenic probes BMP-14 and BMP-16 exhibiting fast PM labeling and extended retention time (over 2 h) on PM. The incorporation of alkyl chains proves effective in promoting the aggregation of BMP-14 and BMP-16 into nonflu

[Identification of transcriptional features and surface markers of plasma cell clones in POEMS syndrome by single-cell RNA sequencing].

POEMS syndrome is a rare monoclonal plasma cell disorder with unique symptoms distinct from other plasma cell neoplasms. To identify and find the transcriptional features of clonal plasma cells in POEMS syndrome (POEMS clones), single-cell RNA sequencing was performed on patient-derived bone marrow plasma cells. POEMS clones were identified in 5 out of 10 patients, and the proportions of POEMS clones in the plasma cells were markedly smaller than that of other plasma cell malignancies such as multiple myeloma and MGUS. The transcriptional features of POEMS clones differed from those of other p…

Is simultaneous presence of IgG4-positive plasma cells and giant-cell hepatitis a coincidence in autoimmune hepatitis? A case report.

BACKGROUND: The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some autoimmune hepatitis. Giant-cell hepatitis (GCH) is a very rare pathological feature in adults, and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear. CASE SUMMARY: A 68-year-old woman was hospitalized with fatigue, poor appetite, and yellow urine for 20 d. Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels. Liver pathology revealed severe inflammation of the interfac…

Extracellular Vesicles in Sickle Cell Disease: Plasma Concentration, Blood Cell Types Origin Distribution and Biological Properties.

Prototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In addition to anemia, SCD patients may exhibit a plethora of clinical manifestations ranging from acute complications such as the frequent and debilitating painful vaso-occlusive crisis to chronic end organ damages. Several interrelated pathophysiologic

A case of AITL complicated by EBV-positive B cell and monoclonal plasma cell proliferation and effectively treated with lenalidomide.

Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma with an aggressive clinical course and poor prognosis after conventional chemotherapy, for which there is no current standard of care. We describe here an 87-year-old woman with AITL, whose clinical diagnosis was complicated by the presence of B immunoblasts positive for Epstein-Barr virus in the lymph nodes and monoclonal plasma cells in the bone marrow at initial presentation. Rebiopsy of the lymph node led to the correct diagnosis of AITL with concurrent smoldering plasma cell myeloma. She was treate…

A possible new morphological variant of mantle cell lymphoma with plasma-cell type Castleman disease-like features.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by overexpression of cyclin D1 resulting from t(11;14)(q13;q32) translocation. Herein, we report 3 cases of MCL with features of plasma cell-type Castleman disease (CD). The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia. Lymph node biopsy specimens of the 3 cases showed histological features of plasma cell-type CD, including atrophic germinal

Rapid Fatal Acute Peripheral T-Cell Lymphoma Associated With IgG Plasma Cell Leukemia and IgA Hypergammaglobulinemia.

Simultaneous occurrence of T-cell and B-cell neoplasms is rare, and etiologic relationships between these 2 malignancies are poorly understood. We describe the case of a 66-year-old woman who was admitted to the hospital because of fever, hemoptysis, lymphadenopathy, and skin rash. Enlarged lymph nodes in axillary, pectoral, paratracheal, and periportal regions as well as slight hepatomegaly and splenomegaly were confirmed. A peripheral blood smear revealed rouleaux formation and numerous circulating plasma cells, with plasmacytoid lymphocytes. Immunofixation-electrophoresis detected a monoclo…

The effect of cidofovir on adenovirus plasma DNA levels in stem cell transplantation recipients without T cell reconstitution.

Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell transplantation (HSCT). However, the antiviral effect irrespective of T cell reconstitution remains unresolved. Plasma HAdV DNA levels were monitored by real-time quantitative PCR during 42 cidofovir treatment episodes for HAdV viremia in 36 pediatric allogeneic HSCT recipients. HAdV load dynamics were related to T and natural killer (NK) cell reconstitution measured by flow cytometry. To evaluate the in vivo antiadenoviral effect of cidofovir, w

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance.

Plasma cell myeloma, characterized by clonally aberrant plasma cells that produce abnormal monoclonal Igs, is the most common indication for autologous hematopoietic progenitor cell transplantation (AHPCT) in North America. We observed appearance of new monoclonal gammopathies different from the original protein in the post-AHPCT setting and termed this condition 'secondary MGUS' (monoclonal gammopathy of undetermined significance). Hence, we performed a retrospective, single institution review of serum protein electrophoresis/immunofixation electrophoresis data in 92 AHPCT recipients from the…

IgA-producing plasma cells originate from germinal centers that are induced by B-cell receptor engagement in humans.

BACKGROUND & AIMS: IgA contributes to homeostatic balance between host and intestinal microbiota. Mechanisms that initiate the IgA response are unclear and likely to differ between humans and animal models. We used multiple experimental approaches to investigate the origin of human intestinal plasma cells that produce IgA in the gastrointestinal tract. METHODS: Complexity of IgA-producing plasma cell populations in human gastrointestinal mucosa and bone marrow and the specific response to oral cholera vaccine were compared by analysis of immunoglobulin genes. Flow cytometry, gene expression a…

Gene expression profiling of plasma cells and plasmablasts: toward a better understanding of the late stages of B-cell differentiation.

Plasma cells (PCs), the end point of B-cell differentiation, are a heterogeneous cell compartment comprising several cell subsets from short-lived highly proliferative plasmablasts to long-lived nondividing fully mature PCs. Whereas the major transcription factors driving the differentiation of B cells to PCs were recently identified, the subtle genetic changes that underlie the transition from plasmablasts to mature PCs are poorly understood. We recently described an in vitro model making it possible to obtain a large number of cells with the morphologic, phenotypic, and functional characteri…

A Mitochondrial Plasma Proteomic Signature Identifies Metastatic Chromophobe Renal Cell Carcinoma.

BACKGROUND: Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC). METHODS: High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix. RESULTS: Differential expression analy

ProFormer: generalizable classification of single-cell and plasma proteomes using deep learning.

Proteins are the main drivers of cell function and disease, making proteomics a powerful technique for biomarker discovery and defining cell identity. While current technologies can profile thousands of proteins and reach single-cell sensitivity, limited throughput restricts applications such as robust classification of large biological or clinical cohorts. To close this gap, we present a deep-learning (DL) approach for the direct analysis of mass spectrometric (MS) data, assigning proteomic profiles to sample identity. Specifically, we introduce the ProFormer, a transformer pipeline that clas

Plasma cell leukemia: genomic features and their potential relevance for exploring clinical actionability.

Plasma cell leukemia (PCL) is rare and aggressive. Plasma cells from patients with PCL were examined using next-generation sequencing (NGS). We compared NGS data from 18 patients with PCL (peripheral blood, n = 10; bone marrow, n = 8) and 1742 multiple myeloma (MM) samples. Mutations of TP53, CCND1, and KRAS were commonly observed in both diseases. Alterations in DIS3 (17% vs 1%), CCND2 (22% vs 15%), PIK3R1 (6% vs 0%), and MAP3K1 (6% vs 2%) were more common in PCL than in MM (P< .05). Translocations occurred in 11 (61.1%) patients with PCL; IGH::CCND1 and IGH::MYC were more frequent in PCL tha…

Plasma COL3A1 propeptide as a promising prognostic marker in oral squamous cell carcinoma.

In this study, we aimed to evaluate the prognostic significance of collagens in patients with oral squamous cell carcinoma (OSCC). Plasma proteomics data from 40 OSCC patients and 33 healthy controls, generated using the Olink Explore 3072 platform, along with microarray gene expression data from 29 OSCC tumours, 21 clinically normal tissues contralateral to tumour (NTCT), and 14 healthy controls, were analysed to assess expression levels of collagens and their associations with clinicopathological variables and survival outcomes. Eleven collagen peptides were detected in plasma. Higher circul

Dietary patterns among individuals with plasma cell disorders- opportunities for targeted interventions.

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… Introduction Plasma cell disorders (PCDs) are a spectrum of diseases characterized by abnormal proliferation of plasma cells, from precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), to malignant multiple myeloma (MM). … Table 1 Healthy Eating Index (HEI) Scores Among Surveyed Plasma Cell Disorder Participants. …

Non-coding RNAs as predictive factors of oncological outcomes in plasma cell myeloma.

Plasma cell myeloma (PCM) is the second most common haematological malignancy and accounts for 1% of all hematological tumors. PCM remains a challenging disease to treat because of its heterogeneity. Despite therapeutic advances, a significant proportion of patients do not respond to treatment or develop resistance, highlighting the need to identify reliable predictive biomarkers. Recent research suggests that non-coding RNAs (ncRNAs), i.e., microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA) are important regulators of gene expression and play a key role in the pathogene

Integrated inference of cancer gene expression from cell-free plasma chromatin.

Gene expression is a defining determinant of tumor identity, behavior, and therapeutic response, yet remains challenging to measure noninvasively. Here, we introduce APEX (Associating Plasma Epigenomic features with eXpression), a framework for inferring expression from circulating cell-free chromatin. Trained on ~270,000 gene-sample pairs from matched tumor RNA-seq and plasma cfChIP-seq across multiple cancers and validated on >15 unseen cancer subtypes, APEX accurately infers cancer gene expression across a range of tumor fractions and outperforms existing plasma-based approaches by integrat

Exploratory analysis of perioperative plasma histamine concentrations in dogs with mast cell tumours.

BACKGROUND: In this exploratory study, we investigated plasma histamine concentration as a perioperative prognostic marker in dogs with mast cell tumours. Mast cell tumours exhibit marked heterogeneity in biological behaviour, and histological grading is widely used for prognostication; however, grading alone does not directly reflect tumour burden or residual disease following surgery. Histamine has a short half-life in the circulation, and persistently elevated plasma histamine levels may reflect continuous release from neoplastic mast cells. Although plasma histamine concentration has been

A rare presentation of plasma cell cheilitis: case report and review of management strategies.

INTRODUCTION AND IMPORTANCE: Plasma cell cheilitis is a rare, benign, and idiopathic inflammatory disorder that affects the lips. This repor … s epithelium, with dense inflammatory infiltrates in the dermis, predominantly consisting of mature plasma cells. Immunohistochemistry analysis demonstrated polyclonal plasma cell positivity for both kappa and lambda light chain markers and significant expression of CD138. Additionally, minor populations of lymphoid cells were identified using CD5, while CD45 …