Peripheral Blood Cell Levels Research Articles

Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial

BackgroundDiabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD).MethodsIn this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA.ResultsPatients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively].ConclusionsPTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs.Trial registrationThe study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009–016595–77). The validation date was 2010-03-09.

Effect of SBRT plus immunotherapy on immune status and survival quality of NSCLC patients: A study of combined radiotherapy and immunotherapy.

non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer populations. Stereotactic radiotherapy (SBRT) is mainly suitable for early NSCLC patients who are not suitable for surgery or refuse surgery. To analyze the effects of stereotactic radiotherapy (SBRT) plus immunotherapy for non-small cell lung cancer (NSCLC) patients on their immune status and survival quality. NSCLC patients admitted to our hospital from 2019-2022 were divided into 61 cases in control group (SBRT) and 60 cases in observation group (SBRT plus immunotherapy) by the randomized numerical table method to compare the efficacy, the level of tumor markers in the serum, the level and activity of the immune cells in the peripheral blood and the Kahlil's functional status (KPS) scores. The observation group had a higher efficacy rate than that of the control group (P< 0.05). There was no statistical difference between the two groups in serum tumor marker content, immune cell level and activity in peripheral blood and KPS score before treatment (P> 0.05). After treatment, serum tumor markers were lower than those in control group, and immune cell level, NK cell-related activity and KPS score were higher than those in control group (P< 0.05). SBRT plus immunotherapy can reduce the level of various tumor markers, improve the immune status and quality of survival for NSCLC patients.

Evaluation of mucosal-associated invariant T-cells as a potential biomarker to predict infection risk in liver cirrhosis.

Infection is a serious complication in patients with cirrhosis. Mucosal-associated invariant T (MAIT) cells are involved in the immune defense against infections and known to be impaired in several chronic conditions, including cirrhosis. Here, we evaluated if MAIT cell levels in peripheral blood are associated with risk of bacterial infections in patients with cirrhosis. Patients with cirrhosis seen at the Karolinska University Hospital, Stockholm, Sweden, between 2016 and 2019 were included. Levels of MAIT cells in peripheral blood were determined using flow cytometry. Baseline and follow-up data after at least two years of follow-up were collected by chart review for the primary outcome (bacterial infection) and secondary outcomes (decompensation and death). Competing risk and Cox regression were performed. We included 106 patients with cirrhosis. The median MAIT cells fraction in the circulation was 0.8% in cirrhosis compared to 6.1% in healthy controls. In contrast to our hypothesis, we found an association in the adjusted analysis between relatively preserved MAIT cell levels, and a slightly higher risk to develop bacterial infections (adjusted subdistribution hazard ratio (aSHR) 1.15 (95%CI = 1.01-1.31). However, MAIT cell levels were not associated with the risk of hepatic decompensation (aSHR 1.19 (95%CI = 0.91-1.56)) nor with death (adjusted hazard ratio 1.10 (95%CI = 0.97-1.22)). Relatively preserved MAIT cell levels in blood of patients with cirrhosis were associated with a somewhat higher risk of bacterial infections. The clinical relevance of this might not be strong. MAIT cells might however be an interesting biomarker to explore in future studies.

FOXP3 full length splice variant is associated with kidney allograft tolerance.

Progressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury. Blood samples were prospectively collected from 333 incident kidney transplant recipients on the first and 29th postoperative day. We used quantitative polymerase chain reaction to determine transcripts of 3 isotypes of FOXP3 splice variants, including pre-mature FOXP3 and full length FOXP3 (FOXP3fl). We investigated the association between FOXP3 splice variant levels and the declines in estimated glomerular filtration rate (eGFR) of more than 5ml/min/1.73m2 within the first-year post-transplant using logistic regression. We observed lower FOXP3fl levels in recipients with declining eGFR (N = 132) than in recipients with stable eGFR (N = 201), (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [4.32 to -3.74], p=0.02). In ad hoc analysis pre-transplant FOXP3fl levels were similar in both groups. The association between FOXP3fl and declining eGFR was confirmed by multivariable analysis adjusted for potential confounding factors (Odds Ratio 0.51, 95% confidence interval 0.28 to 0.91: p=0.02). When stratifying FOXP3fl levels into quartiles, recipients with lower day1 FOXP3fl had the highest rate of declining eGFR (p=0.04). Low FOXP3fl splice variant levels at the first postoperative day in kidney transplant recipients were associated with severe decline of eGFR, a well-known surrogate for hard endpoints.

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

Efficacy of Corticosteroids in the Treatment of Autoimmune Uveitis and its Effect on T Helper Cell and S100 Protein Levels in Peripheral Blood

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients.

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.

Glycyrol Prevents the Progression of Psoriasis-like Skin Inflammation via Immunosuppressive and Anti-Inflammatory Actions.

Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 μmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.

Transient CD4+ T cell depletion during suppressive ART reduces the HIV reservoir in humanized mice.

Lifelong treatment is required for people living with HIV as current antiretroviral therapy (ART) does not eradicate HIV infection. Latently infected cells are essentially indistinguishable from uninfected cells and cannot be depleted by currently available approaches. This study evaluated antibody mediated transient CD4+ T cell depletion as a strategy to reduce the latent HIV reservoir. Anti-CD4 antibodies effectively depleted CD4+ T cells in the peripheral blood and tissues of humanized mice. We then demonstrate that antibody-mediated CD4+ T cell depletion of HIV infected ART-suppressed animals results in substantial reductions in cell-associated viral RNA and DNA levels in peripheral blood cells over the course of anti-CD4 antibody treatment. Recovery of CD4+ T cells was observed in all tissues analyzed except for the lung 26 days after cessation of antibody treatment. After CD4+ T cell recovery, significantly lower levels of cell-associated viral RNA and DNA were detected in the tissues of anti-CD4 antibody-treated animals. Further, an 8.5-fold reduction in the levels of intact HIV proviral DNA and a 3.1-fold reduction in the number of latently infected cells were observed in anti-CD4-antibody-treated animals compared with controls. However, there was no delay in viral rebound when ART was discontinued in anti-CD4 antibody-treated animals following CD4+ T cell recovery compared with controls. Our results suggest that transient CD4+ T cell depletion, a long-standing clinical intervention that might have an acceptable safety profile, during suppressive ART can reduce the size of the HIV reservoir in humanized mice.

Single-Cell RNA Sequencing of Circulating Tumor Cells in Precursor Myeloma Patients Reveals Mechanisms of Disease Dissemination

Introduction Multiple Myeloma (MM) is preceded by the precursors Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), where some patients with precursor disease progress to active MM faster than others. BM biopsies are useful to monitor disease progression, however, they cannot be repeated often for continuous monitoring of tumor burden especially in the precursor disease management setting. Numerous studies have identified circulating tumor cell (CTC) levels in peripheral blood (PB) are a powerful biomarker of disease aggressiveness; CTC levels have associated with disease stage, PFS and OS in various trials and even outperformed BM to assess tumor burden in the SMM setting. Genomic profiling also demonstrated CTCs harbor the same copy number abnormalities, translocations and mutations as BM tumor cells, and CTCs can be serially monitored to detect the emergence of high-risk subclones in the blood. Further investigations of the molecular profile of both normal plasma cells (NPCs) and CTCs are needed to improve our understanding of myeloma pathogenesis and mechanisms of CTC dissemination across the MM disease continuum. Methods A cohort of 309 samples including CD138-enriched paired PB and BM aspirates and matched CD138- BM aspirates were collected from 103 individuals, including patients with MGUS (n=11), SMM (n=46), NDMM (n=17) and healthy donors (n=29). Malignant PCs from BM and PB underwent 5' single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) (10x Genomics), and CD138- BM immune cells underwent 5' scRNA-seq and single-cell T-cell receptor sequencing (scTCR-seq) to study immune alterations related the tumors' ability to circulate. To differentiate malignant from normal PCs, we used clonal V(D)J rearrangements. Differential expression (DE) and composition analyses were conducted using Wilcoxon's rank-sum tests. Results We successfully captured and profiled 774,647 BM tumor cells and 93,878 CTCs from the PB. The percent malignant plasma cells within the PB increased with disease stage, where NDMM patients had significantly more CTCs compared to MGUS patients (p=0.017) and low-risk SMM patients (p=0.0052). A median of 13.51%, 15.53%, and 18.34% CTCs were present from low (n=20), intermediate (n=10), and high-risk (n=16) SMM patients as defined by the International Myeloma Working Group's 2/20/20 criteria, suggesting sequencing-based CTC enumeration captures prognostically relevant differences in tumor burden. High expression of driver genes upregulated in patients with translocations, including CCND1, NSD2, and MAF, were detected in both BM tumor cells and CTCs in patients with t(11;14), t(4;14), and t(14;16) as identified by fluorescence in situ hybridization (FISH). In 5 patients with normal or inconclusive FISH results, we observed high levels of CCND2 and MAF in both BM and CTCs, indicating scRNA-seq can detect missed prognostically relevant cytogenetic abnormalities. A cytogenetic classifier model was developed to determine the accuracy of translocation calling using minimal numbers of CTCs, where the classifier's performance was able to consistently identify translocations downsampled to 50 CTCs. DE analysis of CTCs vs. BM tumor cells highlighted transcriptional similarity between BM and CTCs, validating their utility as a surrogate for analyzing BM tumor cells. DE analysis also revealed 8 genes significantly upregulated and 3 genes significantly downregulated in CTCs compared to BM tumor cells, providing novel insights into genes involved in PC circulatory potential. Pathway enrichment analysis revealed genes upregulated in CTCs were associated with epithelial mesenchymal transition, interferon response, and inflammation, consistent with CTC studies on MM patients, suggesting these pathways are dysregulated earlier in the disease continuum. Conclusions In the largest scRNA-seq study on CTCs to date, we demonstrate the utility of CTC-based molecular profiling for prognostication of patients with early-stage disease and provide novel insights into PC circulatory potential. Additional analyses are ongoing to gain further insight into intra-patient CTC heterogeneity and define high-risk disease CTC signatures that emerge throughout the MM disease continuum.

Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials

BackgroundWhile quadruplet induction therapies deepen responses in newly diagnosed multiple myeloma patients, their impact on peripheral blood stem cell (PBSC) collection remains incompletely understood. This analysis aims to evaluate the effects of prolonged lenalidomide induction and isatuximab- or elotuzumab-containing quadruplet induction therapies on PBSC mobilization and collection.MethodsA total of 179 transplant-eligible patients with newly diagnosed MM treated at a single academic center were included. The patients were evaluated based on PBSC mobilization and collection parameters, including overall collection results, CD34+ cell levels in peripheral blood, leukapheresis (LP) delays, overall number of LP sessions, and the rate of rescue mobilization with plerixafor. The patients underwent four different induction regimens: Lenalidomide, bortezomib, and dexamethasone (RVd, six 21-day cycles, n = 44), isatuximab-RVd (six 21-day cycles, n = 35), RVd (four 21-day cycles, n = 51), or elotuzumab-RVd (four 21-day cycles, n = 49).ResultsThe patients' characteristics were well balanced across the different groups. Collection failures, defined as the inability to collect three sufficient PBSC transplants, were rare (n = 3, 2%), with no occurrences in the isatuximab-RVd and elotuzumab-RVd groups. Intensified induction with six 21-day cycles of RVd did not negatively impact the overall number of collected PBSCs (9.7 × 106/kg bw versus 10.5 × 106/kg bw, p = 0.331) compared to four 21-day cycles of RVd. Plerixafor usage was more common after six cycles of RVd compared to four cycles (16% versus 8%). Addition of elotuzumab to RVd did not adversely affect overall PBSC collection (10.9 × 106/kg bw versus 10.5 × 106/kg bw, p = 0.915). Patients treated with isatuximab-RVd (six cycles) had lower numbers of collected stem cells compared to those receiving RVd (six cycles) induction (8.8 × 106/kg bw versus 9.7 × 106/kg bw, p = 0.801), without experiencing significant delays in LP or increased numbers of LP sessions in a multivariable logistic regression analysis. Plerixafor usage was more common after isatuximab plus RVd compared to RVd alone (34% versus 16%).ConclusionsThis study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy.Trial registrationPatients were treated within the randomized phase III clinical trials GMMG-HD6 (NCT02495922, 24/06/2015) and GMMG-HD7 (NCT03617731, 24/07/2018). However, during stem cell mobilization and -collection, no study-specific therapeutic intervention was performed.

Antiviral and immunostimulatory effects of Ssanti-Covir, a mixed herbal formulation, in cyclophosphamide-treated mice

BackgroundThe novel coronavirus disease 2019 (COVID-19) has raised many concerns among populations worldwide due to its high mortality and morbidity with the lack of treatment options. Many attempts to find preventive and curable approaches have been proposed to prevent infections. The consumption of herbal products or plant extracts was recommended to modulate the body's immunity and reduce the risk of diseases. MethodsIn the current study, we evaluated the anti-viral effects of a mixed herbal formula, named Ssanti-Covir, which was obtained from a combination of 8 herbal species extensively employed in traditional medicine in Vietnam. The objective was to investigate the potential efficacy of Ssanti-Covir against COVID-19 infections in vero E6 cells, as well as its immunostimulatory effects on immunosuppressive mice induced by cyclophosphamide (CP). ResultsThe results of the study revealed that Ssanti-Covir contained significant amounts of andrographolide, silybin A, and silybin B, with concentrations of 137.08 mg/g, 72.01 mg/g, and 81.62 mg/g, respectively. Pre-incubation of Ssanti-Covir at various dilution concentrations effectively prevented cells from being infected by COVID-19, with a viral titer of 100 TCID50/0.1 ml. Oral administration of Ssanti-Covir at doses of 384 mg/kg and 576 mg/kg body weight resulted in a significant increase in the relative weight of the spleen and thymus in mice induced with CP, with p-values of <0.05 and <0.01, respectively, as well as elevated levels of peripheral white blood cells, lymphocytes, neutrophils, and monocytes. Furthermore, all three dosage regimens (192 mg/kg, 384 mg/kg, and 576 mg/kg) also elevated the levels of IL-4, IL-6, TNF-α, IFN-γ cytokines, and IgG in the mice. ConclusionThe research findings suggest that the use of Ssanti-Covir exhibits significant efficacy in preventing COVID-19 infections, while also demonstrating immunostimulatory effects against the CP-induced immunosuppressive model. Consequently, Ssanti-Covir could be employed as a valuable preventive measure or adjuvant treatment for SARS-CoV-2 infections.

Preliminary study on the significance of pathological characteristics analysis of breast cancer and detection of peripheral blood myeloid-derived suppressor cells in the evaluation of biological characteristics

ABSTRACT To explore the significance of the analysis of pathological characteristics of breast cancer and the detection of myeloid-derived suppressor cell (MDSC) levels in peripheral blood for the evaluation of biological characteristics. 138 breast cancer patients were enrolled as the research group, while 138 patients with benign breast diseases were included as the control group. All patients underwent pathological analysis and detection of peripheral blood MDSCs levels, progesterone receptor (PR), estrogen receptor (ER), human epidermal growth factor receptor 2 (HER-2), and proliferating cell nuclear antigen (Ki-67). A factorial study of stage I, II, and III breast cancer patients showed significant differences in clinicopathological characteristics, including age, tumor size, lymph node metastases, histological grading, Neuropsychiatric Inventory (NPI) score, pathological type, and family history (P < 0.05). The research group had higher levels of peripheral blood MDSCs and different cell surface markers compared to the control group (P<0.05). Positive expression of biological molecules in breast cancer, such as PR, ER, HER-2, and Ki-67, had significant differences based on lymph node metastasis and tumor size (P < 0.05). The quality of survival scores was higher in stages I and II compared to stage III (P < 0.05). Age, recurrence, metastasis, and other pathological characteristics of breast cancer have a direct impact on clinical outcomes and survival rates. Peripheral blood levels of MDSCs and other cell surface markers are significantly elevated, serving as a crucial benchmark for the subsequent evaluation of breast cancer progression.

Polatuzumab-bendamustine-rituximab as bridge to CD19-directed CAR T cells in mantle cell lymphoma refractory to ibrutinib and venetoclax.

Polatuzumab-bendamustine-rituximab as bridge to CD19-directed CAR T cells in mantle cell lymphoma refractory to ibrutinib and venetoclax.

Joint Application of Multiple Inflammatory Cytokines in Diagnosis of Gout Flare.

This study aimed to explore the accuracy for joint application of inflammatory cytokines in diagnosis of gout flare by comparison with peripheral blood cells. We collected the clinical data of 96 acute gout patients and 144 remission gout patients, and compared the levels of peripheral blood cells, inflammatory cytokines and blood biochemistry indexes between acute and remission gout. We respectively assessed the area under curves (AUCs) for single and multiple inflammatory cytokines including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and single and multiple peripheral blood cells including platelet (PLT), white blood cell (WBC), percentages of neutrophils (N%), lymphocytes (L%), eosinophils (E%), basophils (B%) in diagnosis of acute gout by receiver operating characteristic (ROC) curve analysis. By contrast with remission gout, the levels of PLT, WBC, N%, CRP, IL-1β, IL-6 and TNF-α increased, and the levels of L%, E% and B% decreased in acute gout. The AUCs of PLT, WBC, N%, L%, E% and B% in diagnosis of acute gout were respectively 0.591, 0.601, 0.581, 0.567, 0.608 and 0.635, while the AUC for joint application of these peripheral blood cells was 0.674. Moreover, the AUCs of CRP, IL-1β, IL-6 and TNF-α in diagnosis of acute gout were respectively 0.814, 0.683, 0.622 and 0.746, while the AUC for joint application of these inflammatory cytokines was 0.883, reflecting significantly higher levels than peripheral blood cells. The joint application of multiple inflammatory cytokines can better distinguish acute gout from remission gout compared with peripheral blood cells.

Correction: Helper T Cell 17 and Regulatory T Cell Levels in Peripheral Blood of Newly Diagnosed Patients with Autoimmune Thyroid Disease: A Meta-Analysis

Correction: Helper T Cell 17 and Regulatory T Cell Levels in Peripheral Blood of Newly Diagnosed Patients with Autoimmune Thyroid Disease: A Meta-Analysis

Increased levels of N6-methyladenosine in peripheral blood RNA: a perspective diagnostic biomarker and therapeutic target for non-small cell lung cancer

Due to lack of effective biomarkers for non-small cell lung cancer (NSCLC), many patients are diagnosed at an advanced stage, which leads to poor prognosis. Dysregulation of N6-methyladenosine (m6A) RNA contributes significantly to tumorigenesis and tumor progression. However, the diagnostic value of m6A RNA status in peripheral blood to screen NSCLC remains unclear. Peripheral blood samples from 152 NSCLC patients and 64 normal controls (NCs) were applied to assess the m6A RNA levels. Bioinformatics and qRT-PCR analysis were performed to identify the specific immune cells in peripheral blood cells and investigate the mechanism of the alteration of m6A RNA levels. Robust elevation of m6A RNA levels of peripheral blood cells was exhibited in the NSCLC group. Moreover, the m6A levels increased as NSCLC progressed, and reduced after treatment. The m6A levels contained area under the curve (AUC) was 0.912, which was remarkably greater than the AUCs for CEA (0.740), CA125 (0.743), SCC (0.654), and Cyfra21-1 (0.730). Furthermore, the combination of these traditional biomarkers with m6A levels elevated the AUC to 0.970. Further analysis established that the expression of m6A erasers FTO and ALKBH5 were both markedly reduced and negatively correlated with m6A levels in peripheral blood of NSCLC. Additionally, GEO database and flow cytometry analysis implied that FTO and ALKBH5 attributes to peripheral CD4+ Tcells proportion and activated the immune functions of Tcells. These findings unraveled that m6A RNA of peripheral blood immune cells was a prospective biomarker for the diagnosis of NSCLC.

Helper T Cell 17 and Regulatory T Cell Levels in Peripheral Blood of Newly Diagnosed Patients with Autoimmune Thyroid Disease: A Meta-Analysis.

This article aims to explore associated immune indicators of autoimmune thyroid disease (AITD) through a meta-analysis of published case-control studies on newly diagnosed AITD patients, intending to provide some suggestions for research on the mechanisms of AITD. Six electronic databases were searched for case-control studies on newly diagnosed AITD patients from inception to August 15, 2022. A random-effects model was used to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (95% CI). A total of 26 articles were included in this meta-analysis. Patients with newly diagnosed AITD had higher levels of helper T cell 17 (Th17) (Hashimoto's disease (HT): SMD=2.35, 95% CI: 1.98, 2.72; Graves' disease (GD): SMD=1.61, 95% CI: 1.23, 1.98), lower levels of regulatory T cell (Treg) (HT: SMD=-2.04, 95% CI: -2.67, -1.42; GD: SMD=-1.35, 95% CI: -2.11, -0.58), and lower levels of forkhead box P3 (FoxP3) mRNA (HT: SMD=-2.58, 95% CI: -3.12, -2.05; GD: SMD=-2.13, 95% CI: -2.56, -1.70), compared to the healthy population. In addition, the single nucleotide polymorphism rs3761548 and rs3761549 in the promoter region of FoxP3 showed a higher frequency in the comparison of genotype "CT" only in HT patients than in the healthy population (OR=1.66, 95%CI: 1.18, 2.34). In patients with newly diagnosed AITD, the Th17/Treg ratio imbalance may develop AITD. Monitoring Th17 and Treg levels may become an essential tool to assess the organism's immune homeostasis and hopefully guide clinical diagnosis and treatment.

Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders.

To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion. We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion. Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment. Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.

Mer-tyrosine kinase: a novel susceptibility gene for SLE related end-stage renal disease

ObjectiveLupus nephritis (LN) is a common and severe manifestation of SLE. The genetic risk for nephritis and progression to end-stage renal disease (ESRD) in patients with LN remains unclear. Herein,...

Increased Phospho-AKT in Blood Cells from LRRK2 G2019S Mutation Carriers.

The purpose of this study was to investigate whether differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). We assessed phospho(P)-Ser-935-LRRK2 and P-Ser-473-AKT levels in peripheral blood cells from patients with G2019S LRRK2-associated PD (L2PD, n=31), G2019S LRRK2 non-manifesting carriers (L2NMC, n=26), idiopathic PD (iPD, n=25), and controls (n=40, total n=122). We found no differences at P-Ser-935-LRRK2 between groups but detected a specific increase of P-Ser-473-AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD. Although insensitive to LRRK2 inhibition, our study identifies P-Ser-473-AKT as an endogenous candidate biomarker for peripheral inflammation in G2019S carriers using accessible blood cells. ANN NEUROL 2022;92:888-894.