Proportion Of Plasma Cells Research Articles

Multiomics identification of ALDH9A1 as a crucial immunoregulatory molecule involved in calcific aortic valve disease

Mitochondrial dysfunction and immune cell infiltration play crucial yet incompletely understood roles in the pathogenesis of calcific aortic valve disease (CAVD). This study aimed to identify immune-related mitochondrial genes critical to the pathological process of CAVD using multiomics approaches. The CIBERSORT algorithm was employed to evaluate immune cell infiltration characteristics in CAVD patients. An integrative analysis combining weighted gene coexpression network analysis (WGCNA), machine learning, and summary data-based Mendelian randomization (SMR) was performed to identify key mitochondrial genes implicated in CAVD. Spearman’s rank correlation analysis was also performed to assess the relationships between key mitochondrial genes and infiltrating immune cells. Compared with those in normal aortic valve tissue, an increased proportion of M0 macrophages and resting memory CD4 T cells, along with a decreased proportion of plasma cells and activated dendritic cells, were observed in CAVD patients. Additionally, eight key mitochondrial genes associated with CAVD, including PDK4, LDHB, SLC25A36, ALDH9A1, ECHDC2, AUH, ALDH2, and BNIP3, were identified through the integration of WGCNA and machine learning methods. Subsequent SMR analysis, incorporating multiomics data, such as expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (mQTLs), revealed a significant causal relationship between ALDH9A1 expression and a reduced risk of CAVD. Moreover, ALDH9A1 expression was inversely correlated with M0 macrophages and positively correlated with M2 macrophages. These findings suggest that increased ALDH9A1 expression is significantly associated with a reduced risk of CAVD and that it may exert its protective effects by modulating mitochondrial function and immune cell infiltration. Specifically, ALDH9A1 may contribute to the shift from M0 macrophages to anti-inflammatory M2 macrophages, potentially mitigating the pathological progression of CAVD. In conclusion, ALDH9A1 represents a promising molecular target for the diagnosis and treatment of CAVD. However, further validation through in vivo and n vitro studies is necessary to confirm its role in CAVD pathogenesis and therapeutic potential.

Systematic literature review of published cases of reactive plasmacytosis in peripheral blood and bone marrow

AimsThis study aims to summarise published cases of reactive plasmacytosis to provide a resource to aid haematopathologists and clinicians in the diagnostic workup of reactive plasmacytosis.MethodsWe searched published articles on...

REACTION OF LYMPHOID TISSUE IN THE WALL OF THE DUODENUM AND LYMPHOID PLAQUE IN RATS IN MODELING HYPOKINESIA

The damaging effect of hypokinesia on the functional state of lymphoid tissue in the wall of the duodenum and on the lymphoid plaque was established. It was found that the processes of cell destruction, suppression of the plasma reaction and blast transformation of cells are most pronounced in the wall of the duodenum. In the lymphoid plaque, along with a high level of destructive processes in lymphoid cells, lymphocytopoiesis is preserved in the centers of proliferation of lymphoid nodules and the proportion of plasma cells increases in the internodal zone, which indicates the development of compensatory processes under the long-term influence of hypokinesia.

Divergent immune profiles in distinct populations - A vietnamese-german comparison

The human immune system exhibits fascinating diversity, sculpted by an intricate interplay of genetic and environmental influences. This study delves into these complexities by comparing the immunological landscapes of healthy individuals from distinct backgrounds: 40 Vietnamese and 24 German participants. Our comprehensive analysis, encompassing 42 lymphocyte populations and 17 cytokines, reveals profound differences in immune profiles between these two populations. Utilizing multicolor flow cytometry and advanced analytical platforms, we conducted a comprehensive characterization of the cellular and molecular components of individual immune systems. Statistical analyses revealed highly significant differences (p < 0.05) between Vietnamese and German cohorts in 33 out of 42 lymphocyte populations and 15 out of 17 cytokines. These disparities encompassed a wide range of immune cell subsets, including T, B and NK cells and involved both activating and inhibitory immune regulators. Healthy Vietnamese subjects exhibited significantly higher numbers of B, T and NK cells compared to their German counterparts. Vietnamese participants displayed higher proportions of plasma cells, immature B cells, and B cells with low CD21 expression (CD21low), which have a phenotypic characteristic of chronic stimulation. Of the 16 subpopulations of CD4+ and CD8+ T cell subpopulations, 11 were significantly elevated in Vietnamese compared to German subjects. Additionally, Vietnamese participants expressed higher proportions of markers for functional and activating NK receptors, indicating the presence of highly cytotoxic NK cells in this population. Almost all of the 17 cytokines examined were significantly lower in Vietnamese subjects. These results demonstrate statistically significant variations in immunological profiles between healthy individuals from Eastern and Western populations. Our findings suggest that caution should be exercised when applying Western reference health profiles to Eastern subjects in clinical settings. This comprehensive analysis underscores the importance of considering population-specific immune profiles in clinical and research contexts, particularly when evaluating immunological parameters across diverse ethnic groups.

Correlation analysis of polyclonal plasma cell proportion in the bone marrow with clinical characteristics of patients with newly diagnosed multiple myeloma

Objective: To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed. Results: A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages (P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams (P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 (P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and β(2)-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and β(2)-microglobulin at the initial diagnosis (P<0.05) ; lower HGB level (P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ (P=0.034) . Conclusion: In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, β(2)-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.

Abstract PO4-24-12: Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate

Abstract Background Breast cancers (BC) in the young women tend to have poor outcomes and higher proportion of aggressive subtypes. Immunotherapy has shown promising results lately, especially for aggressive categories like triple negative breast cancers (TNBC). Success of the immunotherapy is shown to be dependent on the tumor immune microenvironment (TIME) which plays important role in disease progression and response to therapy. Though numerous studies have demonstrated immune hot tumors are associated with better prognosis, mechanism of immunologically hot TIME is not yet deciphered. Material and methods Gene expression data derived from RNA sequencing (n=40) of primary BC was used to divide them into immune hot and cold tumors by using 15 gene signature (Wang et al., Sci. Adv. 2021). Average expression of the hot and cold (hot=12 and cold=3) genes was derived for each tumor and median value of their ratio was used to categorize them into immunologically hot and cold tumors. Association of the hot and cold tumors with clinical characteristics was examined. CIBERSORT algorithm was used to identify immune cell subtypes and Kaplan Meier survival analysis was performed to assess the prognostic significance. Similar analysis was replicated in TCGA (n=1083) dataset. Results Equal proportion of immune hot and cold tumor was observed in the cohort. Higher proportion of cold tumors were observed in younger and premenopausal (p=0.002) patients. Subtype analysis showed higher proportion of cold tumors in TNBC compared to hormone receptor positive tumors (p&amp;lt; 0.0001). No significant difference was observed in other clinicopathological characteristics between the groups. Further analysis of cold tumors for immune cell subtypes, categorized by the menopausal status showed higher proportion of plasma cells and CD4 memory resting cells and lower proportion of M2 macrophages and B memory cell in premenopausal (n=129, TCGA) compared postmenopausal (n=322, TCGA) tumors. In addition, premenopausal cold tumors were associated with better overall survival compared to postmenopausal group (p=0.001). Conclusion Younger premenopausal women with BC are likely to have more immunologically cold tumors. Though circulating levels of sex steroid hormones is the predominant difference between the pre and postmenopausal women, its influence on TIME and therapeutic significance must be explored. Citation Format: Vidya P Nimbalkar, Snijesh VP, Savitha Rajarajan, Annie Alexander, Rakesh Ramesh, B S Srinath, Jyothi S Prabhu. Premenopausal breast cancers show higher proportion of immunologically cold tumors and are associated with distinct immune cell infiltrate [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-12.

Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing

BackgroundDimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking.MethodsTo explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF.ResultsOur study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells.ConclusionsDMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.

Enhanced therapeutic effects of apoptotic cell‐conditioned mesenchymal stem cells in lupus‐prone MRL/lpr mice

AbstractBackgroundApoptotic cell‐conditioned mesenchymal stem cells (AC‐MSCs) exhibit stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2); however, whether AC‐MSCs exhibit enhanced therapeutic effects on systemic lupus erythematosus (SLE) remains unknown.MethodsSplenocytes from MRL/MPJ‐Faslpr (MRL/lpr) mice were cocultured with AC‐MSCs, and the proportion of plasma cells was determined by flow cytometry. MSCs, AC‐MSCs, COX2 knockdown MSCs, and COX2 knockdown AC‐MSCs were infused into MRL/lpr mice (n = 10/group). Survival rates and lupus symptoms, including proteinuria, kidney injury, renal immune complex deposition, and autoantibody production, were assessed. Additionally, the number of plasma cells and serum levels of inflammatory cytokines were measured.ResultsThe AC‐MSCs significantly inhibited plasma cells via PGE2 after 24 h coculture in vitro, whereas MSCs did not. In the MRL/lpr mice, AC‐MSC treatment led to a significantly higher survival rate than phosphate‐buffered saline (PBS) treatment (90% vs. 50%, p &lt; 0.05). Moreover, AC‐MSC infusion decreased urine protein levels as early as 1 week after administration (0.89 ± 0.55 mg/mL vs. 1.59 ± 0.60 mg/mL, p &lt; 0.05, compared with PBS treatment). Administration of both MSCs and AC‐MSCs reduced renal immunoglobulin G and complement C3 deposition, whereas COX2 knockdown MSCs and COX2 knockdown AC‐MSCs did not. Serum anti‐dsDNA antibody levels in AC‐MSC‐treated mice significantly decreased (0.40 ± 0.25 vs. 0.99 ± 0.58, p &lt; 0.05), compared with PBS treatment, as well as the number of plasma cells in both the spleen ([2.14 ± 1.05] × 106 vs. [8.02 ± 4.01] × 106, p &lt; 0.01) and renal‐draining lymph nodes ([0.78 ± 0.68] × 106 vs. [2.49 ± 1.45] × 106, p &lt; 0.05). Additionally, AC‐MSCs inhibited the production of inflammatory cytokines, including interleukin‐21, tumor necrosis factor‐alpha, and monocyte chemoattractant protein‐1.ConclusionsAC‐MSCs enhanced the therapeutic effects in mice with lupus, which were partially mediated by COX2/PGE2. Therefore, AC preconditioning may be a new strategy for MSC transplantation in the treatment of SLE.

A Case of Lymphoplasmacytic Cell Lymphoma Characterized by Marked Nuclear Fission and Brain Gyrus Nuclei of Lymphocytes

A 67-year-old male was admitted to the hospital due to fatigue and thrombocytopenia. Peripheral blood cells analysis showed the white blood cells count of 2.99 × 109 /L, red blood cell (RBC) count of 2.08 × 1012/L, platelet count of 15 × 109 /L. β2- microglobulin of serum was 5.50 mg/L. Whole-body positron emission tomography-computed tomography suggested altered reactivity in the lymph nodes of the bilateral neck. Morphological examination of bone marrow (BM) indicated the presence of abnormal smaller lymphocytes, accounting for 12.5% of the total nucleated cells. Strikingly, nuclear fission or brain gyrus nuclei were prominently observed in all abnormal lymphocytes (Figure 1, original magnification 1000×; Wright–Giemsa stain). The proportion of plasma cells was 0.5%, and no morphological abnormalities were observed. Additionally, some RBCs were exhibited a rouleaux arrangement. Flow cytometry analysis of BM identified 16.12% of κ-restricted B lymphocytes expressing CD5- , CD10- , CD19+ , CD20+ . A minimal proportion of 0.03% plasma cells with κ/λ ratio of 1.07. Consistent results were confirmed by immunohistochemistry in the BM biopsy. Immunofixation electrophoresis revealed abnormal monoclonal bands in the IgM and κ lanes. Furthermore, mutations of MYD88 (L265P), CXCR4 (T318fs), and TP53 (R306X) were identified through next-generation sequencing analysis. A diagnosis of lymphoplasmic cell lymphoma/waldenström macroglobulinemia (LPL/WM) was established.

Preliminary findings on the development of a predictive model for BLCA based on disulfidptosis-associated IncRNAs signature

BackgroundBladder urothelial carcinoma (BLCA) is the most common malignancy of the urinary tract, presenting with a wide range of clinical symptoms and prognosis. Disulfidptosis is a newly identified cell death method and closely associated with BLCA progression, prognosis, and treatment outcome. Currently, we need to construct a new prognostic model for disulfidptosis-related long noncoding RNAs (drlncRNAs) to improve the treatment strategy of BLCA.MethodsThe data for BLCA samples were obtained from The Cancer Genome Atlas (TCGA), and then 10 unique genes related to disulfidoptosis (DRGs) were identified from research papers. The differences between the two groups showed in this study were used to create the “disulfidptosis-related long noncoding RNAs score” (disulfidptosis-score) prognostic model.ResultsWe identified two groups of drlncRNAs with high and low disulfidptosis scores in this study. Patients with low disulfidptosis scores had a better overall survival rate compared to those with high scores in bladder cancer, and the high disulfidptosis score subtype exhibited more active malignant pathways related to cancer than the low score subtype. We found that the low disulfidptosis-score subgroup had better prognosis than the high disulfidptosis-score subgroup. The expression of mutation burden was much higher in the low disulfidptosis-score group than in the high disulfidptosis-score group. The low disulfidptosis-score subgroup of patients exhibited significantly higher proportions of plasma cells, T cells CD8, and Tregs, while the high-risk subgroup had a greater abundance of Macrophages M0 and Macrophages M2. The disulfidptosis-score showed a strong correlation with the sensitivity of chemotherapeutic drugs, and patients in the low disulfidptosis-score group were more likely to exhibit an immune response and respond positively to immunotherapy. Additionally, we developed a nomogram to enhance the accuracy of the disulfidptosis-clinical score.ConclusionBased on our investigation of disulfidptosis-score in BLCA, disulfidptosis-score may have an important role in TME, prognosis, and drug sensitivity. We also investigated the significance of the disulfidoptosis-score in relation to immunotherapy and immune response, providing a basis for improving prognosis and responding to immunotherapy among patients with BLCA.

Status of B-Lymphocyte Subsets and Their Homing Markers in Patients With Post-Kala-Azar Dermal Leishmaniasis.

In visceral leishmaniasis, the Type II helper T cell predominance results in B cell modulation and enhancement of anti-leishmanial IgG. However, information regarding its dermal sequel, post-kala-azar dermal leishmaniasis (PKDL), remains limited. Accordingly, this study aimed to elucidate the B cell-mediated antibody-dependent/independent immune profiles of PKDL patients. In the peripheral blood of PKDL patients, immunophenotyping of B cell subsets was performed by flow cytometry and by immunohistochemistry at lesional sites. The functionality of B cells was assessed in terms of skin IgG by immunofluorescence, while the circulating levels of B cell chemoattractants (CCL20, CXCL13, CCL17, CCL22, CCL19, CCL27, CXCL9, CXCL10 and CXCL11) were evaluated by a multiplex assay. In patients with PKDL as compared with healthy controls, there was a significant decrease in pan CD19+ B cells. However, within the CD19+ B cell population, there was a significantly raised proportion of switched memory B cells (CD19+IgD-CD27+) and plasma cells (CD19+IgD-CD38+CD27+). This was corroborated at lesional sites where a higher expression of CD20+ B cells and CD138+ plasma cells was evident; they were Ki67 negative and demonstrated a raised IgG. The circulating levels of B cell chemoattractants were raised and correlated positively with lesional CD20+ B cells. The increased levels of B cell homing markers possibly accounted for their enhanced presence at the lesional sites. There was a high proportion of plasma cells, which accounted for the increased presence of IgG that possibly facilitated parasite persistence and disease progression.

Immunohistological analysis reveals IgG1-dominant immunophenotype of tubulointerstitial nephritis unassociated with IgG4-related diseases

PurposeTubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis.MethodsThe study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry.ResultsIgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group.ConclusionThe present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.

Are sonographic characteristics of Hashimoto's thyroiditis related with immunologic parameters? A cross-sectional study.

The clinical, laboratory, and imaging characteristics of Hashimoto's thyroiditis are widely recognized. However, there is a dearth of information concerning the relationship between these aspects. The primary objective of this study was to investigate the correlation between sonographic features and immunologic parameters in individuals with Hashimoto's thyroiditis. This cross-sectional study enrolled a cohort of 100 consecutive patients diagnosed with Hashimoto's thyroiditis. Ultrasonography was performed to classify thyroid gland characteristics, including parenchymal heterogeneity (mild/moderate-to-high), extent of fibrosis (none-to-mild/moderate-to-high), and volume (atrophic/non-atrophic). As for immunologic parameters, thyroid autoantibodies (TOA; anti-TPO and anti-Tg), along with IG (immunoglobulin) G4 levels and lymphocyte subsets, were assessed. Of the 100 patients evaluated, 88 were female (88%) and 12 were male (12%). IgG4/IgG ratio and weekly levothyroxine (LT4) dose were significantly higher in the group with moderate-to-high heterogeneity than the group with mild parenchymal heterogeneity (p = 0.043 and p < 0.001, respectively). Compared to the group with none-to-mild fibrosis, the anti-TPO, IgG4, IgG4/IgG ratio and LT4 dose were significantly higher in the moderate-to-high fibrosis group. Anti-TPO and IgG levels were significantly lower in the atrophic thyroid group compared to the non-atrophic thyroid group. Although not reaching statistical significance, the proportion of plasma cells in the moderate/high fibrosis group was higher than in the non-fibrosis/mild fibrosis group. There was a moderate positive correlation between fibrosis with Anti-TPO, and a low positive correlation between anti-Tg, IgG4 levels with IgG4/IgG ratio. TOA, Ig G4 levels and severity of hypothyroidism were associated with ultrasonographic features such as parenchymal heterogeneity and fibrosis in Hashimoto's thyroiditis.

Potential therapeutic targets for pelvic organ prolapse: insights from key genes related to blood vessel development.

Pelvic organ prolapse (POP) is a disease in which pelvic floor support structures are dysfunctional due to disruption of the extracellular matrix (ECM). The vascular system is essential for maintaining ECM homeostasis. Therefore, this study explored the potential mechanism of blood vessel development-related genes (BVDRGs) in POP. POP-related datasets and BVDRGs were included in this study. Differentially expressed genes (DEGs) between the POP and control groups were first identified in the GSE12852 and GSE208271 datasets, and DE-BVDRGs were identified by determining the intersection of these DEGs and BVDRGs. Subsequently, the feature genes were evaluated by machine learning. Feature genes with consistent expression trends in the GSE12852 and GSE208271 datasets were considered key genes. Afterward, the overall diagnostic efficacy of key genes in POP was evaluated through receiver operating characteristic (ROC) curve analysis. Based on the key genes, enrichment analysis, immune infiltration analysis and regulatory network construction were performed to elucidate the molecular mechanisms underlying the functions of the key genes in POP. A total of 888 DEGs1 and 643 DEGs2 were identified in the GSE12852 and GSE208271 datasets, and 26 candidate genes and 4 DE-BVDRGs were identified. Furthermore, Hyaluronan synthase 2 (HAS2), Matrix metalloproteinase 19 (MMP19) and Plexin Domain Containing 1 (PLXDC1) were identified as key genes in POP and had promising value for diagnosing POP (AUC > 0.8). Additional research revealed that the key genes were predominantly implicated in immune cell activation, chemotaxis, and cytokine release via the chemokine signaling pathway, the Nod-like receptor signaling pathway, and the Toll-like receptor signaling pathway. Analysis of immune cell infiltration confirmed a decrease in the proportion of plasma cells in POP, and MMP19 expression showed a significant negative correlation with plasma cell numbers. In addition, regulatory network analysis revealed that MALAT1 (a lncRNA) targeted hsa-miR-503-5p, hsa-miR-23a-3p and hsa-miR-129-5p to simultaneously regulate three key genes. We identified three key BVDRGs (HAS2, MMP19 and PLXDC1) related to the ECM in POP, providing markers for diagnostic studies and investigations of the molecular mechanism of POP.

Clinicopathological Characteristics and Outcome of Cytophagic Histiocytic Panniculitis: A Single-Center, Retrospective Study.

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge. Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022. All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal. The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.

TLR7 enhancing follicular helper T (Tfh) cells response in C57BL/6 mice infected with Plasmodium yoelii NSM TLR7 mediated Tfh cells in P. yoelii infected mice.

Toll-like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll-like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4+ CXCR5+ PD-1+ Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down-regulated expression of functional molecules CD40L, IFN-γ, IL-21 and IL-10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM-infected mice.

Single-cell RNA sequencing reveals the immune microenvironment landscape of osteosarcoma before and after chemotherapy

Chemotherapy, a primary treatment for osteosarcoma (OS), has limited knowledge regarding its impact on tumor immune microenvironment (TIME). Here, tissues from 6 chemotherapy-naive OS patients underwent single-cell RNA sequencing (scRNA-seq) and were analyzed alongside public dataset (GSE152048) containing 7 post-chemotherapy OS tissues. CD45+ (PTPRC+) cells were used for cell clustering and annotation. Changes in immune cell composition pre- and post-chemotherapy were characterized. Totally, 28,636 high-quality CD45+ (PTPRC+) cells were extracted. Following chemotherapy, the proportions of regulatory T cells (Tregs) and activated CD8 T cells decreased, while CD8 effector T cells increased. GO analysis indicated that differentially expressed genes (DEGs) in T cells were associated with cell activation, adaptive immune response, and immune response to tumor cells. Furthermore, the proportions of plasma cells increased, while naive B cells decreased. B cell surface receptors expression was upregulated, and GO analysis revealed DEGs of B cells were mainly enriched in B cell-mediated immunity and B cell activation. Moreover, M2 polarization of macrophages was suppressed post-chemotherapy. Overall, this study elucidates chemotherapy remodels the OS TIME landscape, triggering immune heterogeneity and enhancing anti-tumor properties.

The Therapeutic Efficacy of CD19 Chimeric Antigen Receptor T Cells in Immune Thrombocytopenia Model

Abstract Introduction: ITP is a hemorrhagic autoimmune disease characterized by excessive platelet destruction and impaired platelet production,resulting in a high risk of bleeding. The pathogenesis of ITP involves immune intolerance towards platelet antigen, with platelet autoantibodies produced by plasma cells playing a significant role. Current treatments targeting this pathogenesis mainly rely on CD20 monoclonal antibodies, such as rituximab. However, as CD20 expression is present at the pre-B cell and mature B cell stages but absent on the surface of mature plasma cells. This can explain why a subset of autoantibody-positive patients do not respond to B-cell depletion therapy. CAR-T cell therapy, a form of adoptive cellular immunotherapy, has shown great potential in hematological malignancies and solid tumors. Recent studies have demonstrated its potential effectiveness of CAR-T cell therapy in various autoimmune diseases. CD19, expressed at all stages of B cell differentiation, presents an opportunity for CAR-T cell therapy in ITP. This study aims to evaluate the efficacy of CD19 CAR-T cell immunotherapy in an active murine ITP model. Methods: CD42-knockout mice were immunized with wild type (WT) C57BL/6 mice and splenocytes from these immunized mice were transplanted into irradiated WT mice to construct a murine model of active ITP. The ITP mice were then randomized into two groups, with the experimental group receiving an intraperitoneal injection with 1×10 6 CD19 CAR-T cells. Platelet counts were monitored weekly, and after 3 weeks, the ITP mice were euthanized and sacrificed. Single-cell suspensions were prepared from harvested spleens for analysis. Anti-murine antibodies were analyzed using flow cytometry (Beckmann Coulter, Brea, CA, USA). All data were analyzed by Statistical Package for the Social Sciences (SPSS) software, version 25.0 (IBM Corp., Armonk, NY, USA). P &amp;lt; 0.05 was considered statistically significance. Results: Our results demonstrated that the platelet counts of ITP mice reached their lowest level on day 7 after spleen cell transplantation, gradually recovering within a week. Platelet counts were significantly higher in the CD19 CAR-T cell therapy group compared to the control group on day 7 and persisted until day 21. There were no significant differences in weight between two groups, indicating no severe complication or CRS were identified. In the third week CD19 CAR-T cell therapy, the proportion of plasma cells in the spleen was determined, showing a marked decrease in the percentage of CD138+ plasma cells in the CAR-T group compared to the control group. Additionally, at day 14, the titers of anti-platelet CD42-specific antibodies were significantly lower in the CAR-T cell treated group compared to the control group. Furthermore, the mean fluorescence intensity (MFI) of CD19+ B cells in the spleen cells of the CD19 CAR-T cell immunotherapy group was significantly decreased compared to the control group. Conclusion: This study demonstrates the effectiveness of CD19 CAR-T cell therapy in treating thrombocytopenia by suppressing plasma and B cells in a mouse model of active ITP. These findings provide valuable insights into the potential therapeutic application of CD19 CAR-T cell immunotherapy for immune thrombocytopenia. Disclosure: No conflict of interest.

CPXM1 correlates to poor prognosis and immune cell infiltration in gastric cancer

BackgroundGastric cancer (GC) is the fourth most common cause of cancer-related death and the fifth most frequent malignant cancer, especially advanced GC. Carboxypeptidase X member 1 (CPXM1) is an epigenetic factor involved in many physiological processes, including osteoclast differentiation and adipogenesis. Several studies have shown the association of CPXM1 with multiple tumors; however, the mechanism of CPXM1 involvement in the progression of GC is yet to be characterized. MethodCPXM1 expression data were obtained from the Tumor Immune Estimation Resource. The Cancer Genome Atlas and the Gene Expression Omnibus databases were used to obtain patient-matched clinicopathological information, and the Kaplan–Meier plot database was utilized for the prognosis analysis of GC patients. The Catalog of Somatic Mutations in Cancer and cBioportal databases were adopted to study CPXM1 mutations in tumors. Next, we utilized the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis for mechanism research. Furthermore, we performed tumor microenvironment and immune infiltration analysis based on CPXM1. Finally, we predicted sensitivity to several targeted drugs in GC patients based on CPXM1.CPXM1 is upregulated in GC and is correlated with poor prognosis, gender, and tumor stage in GC patients. Gene enrichment analysis suggested that CPXM1 may regulate the occurrence and progression of GC via the PI3K–AKT and TGF-β pathway. Moreover, CPXM1 expression results in an increase in the proportion of immune and stromal cells. Additionally, the proportion of plasma cells was inversely related to the expression of CPXM1, whereas macrophage M2 expression was proportionate to CPXM1 expression. Finally, six small-molecule drugs that showed notable variations in IC50 between two groups were screened. ConclusionThese results suggested that CPXM1 regulates the progression of GC and may represent a novel target for the detection and treatment of GC.

Identification of genes related to glucose metabolism and analysis of the immune characteristics in Alzheimer's disease

ObjectiveGlucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. MethodsAD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. ResultsA total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and γ-δ T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. ConclusionsThe diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.