sCD14 Levels Research Articles

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy.

The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin-hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy.

The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis

Introduction and objectivesDiabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. Materials and methodsMid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3–V4 region of the bacterial 16S rRNA gene. Correlations with the patients’ clinical data and inflammatory profile were performed. ResultsCKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14. ConclusionsOur results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.

Abstract A002: Serum levels of immune markers associated with pathological complete response (pCR) and immune-related adverse events (irAEs) in early-stage breast cancer patients receiving immune checkpoint inhibitor plus chemotherapy in the I-SPY 2 trial

Abstract Background: Surrogate biomarkers of efficacy and AEs are needed for therapy with immune checkpoint inhibitors (ICI). Although ICI treatments have demonstrated effectiveness in combating early-stage breast cancer (BC), predicting early response and the associated risk of irAEs are important considerations. In this study, we evaluated pre-treatment, early on-treatment, and early changes of serum immune markers in women with BC treated with neoadjuvant chemotherapy plus an ICI. Methods: Serum samples were obtained from 49 women with early stage HER2-negative BC enrolled in the I-SPY 2 trial who received paclitaxel plus an ICI (anti-PD-1) followed by anthracycline/cyclophosphamide. Serum was collected at baseline (T0) and 3 weeks after the first dose (T1). Serum samples were assayed by Ella multiplex immunoassays for 18 pre-selected immune markers, including soluble immune checkpoint molecules (sPD-L1, LAG-3), cytokines (IL-6, IL-8, IFNg, TNFa, IL-10, G-CSF, MCP-1), chemokines (CXCL9, CXCL10, CXCL11, CXCL13), molecules associated with angiogenesis/lymphangiogenesis (VEGF-C), and other markers reflecting immune inflammation/activation (C-Reactive Protein [CRP], CD163, sCD25, GranzymeB). Serum markers showing significant changes from T0 to T1 were identified with the Wilcoxon test. Associations between absolute levels or changes in serum markers and response to therapy (pCR) and/or irAEs were assessed with the Mann–Whitney test. Results: Serum IFNg, G-CSF, IL-10, LAG-3, CCL2, CXCL-10, sCD25, CXCL-9 and CXCL-11 significantly increased between T0 and T1 (P <0.0001, 0.014, <0.001, 0.043, <0.0001, 0.032, <0.0001, <0.0001, <0.0001, respectively). In hormone-receptor positive (HR+)/HER2- patients (N=29), low baseline IFNg serum levels were associated with response to therapy (P = 0.04). In addition, a decrease in sCD25 serum levels from T0 to T1 was strongly associated with response (P = 0.0047) in all HER2- patients. Immune-related AEs were reported for a small number of patients (N=9/49). Increases in serum levels of VEGF-C from T0 to T1 were significantly associated with irAEs (P = 0.0055). In addition, patients who developed irAEs had significantly higher T0 and T1 levels of CD163 (P = 0.022 and 0.024, respectively). Conclusions: Baseline serum level of IFNg and early changes in serum sCD25 levels could be used to monitor and predict clinical benefit from anti-PD-1 agents. This study also suggests that VEGF-C and CD163 may serve as possible candidate prognostic biomarkers for irAEs in patients receiving anti-PD-1 therapy in the early-stage BC setting. While our preliminary results are promising, additional validation in a larger sample size is crucial to confirm the observed trends. Therefore, candidate biomarkers from additional I-SPY 2 arms containing ICIs will be analyzed. Citation Format: Silver Alkhafaji, Denise M. Wolf, Amrita Basu, Lamorna Brown-Swigart, Rita Nanda, Minneta Liu, Gillian L. Hirst, Laura J. Esserman, Laura van 't Veer, Michael Campbell. Serum levels of immune markers associated with pathological complete response (pCR) and immune-related adverse events (irAEs) in early-stage breast cancer patients receiving immune checkpoint inhibitor plus chemotherapy in the I-SPY 2 trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A002.

Soluble CD27 as a predictive biomarker for intra-tumoral CD70/CD27 interaction in nasopharyngeal carcinoma.

In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

The clinical significance of plasma sCD25 as valuable biomarker for progression and prognosis of tuberculosis

BackgroundsCD25 is an important immune molecule for T cell regulation. Tracking the detection of plasma sCD25 plays an important role in the evaluation of immune function, progression, and prognosis of tuberculosis (TB) patients. This study analyzed the association of plasma sCD25 levels with clinical, laboratory, CT imaging characteristics, and clinical outcome of TB patients.MethodsThe clinical data of 303 TB patients treated in the Fifth People’s Hospital of Suzhou from October 2019 to January 2022 were retrospectively analyzed. The levels of sCD25 in plasma were detected by ELISA. According to the cut-off threshold of plasma sCD25 levels, the patients were divided into a low-value group (Group TB1) and a high-value group (Group TB2). The association of plasma sCD25 levels with clinical, laboratory, and CT imaging characteristics of TB patients, as well as their TB treatment outcome were analyzed.ResultsThe levels of plasma sCD25 of patients with TB patients were higher than that of the healthy control group (P < 0.01). Among the 303 TB patients, the levels were increased in Group TB2 patients (0.602 ± 0.216 vs. 1.717 ± 0.604 ng/ml, P < 0.001), and there was a progressive reduction after anti-TB treatment. Furthermore, patients in Group TB2 showed higher positive rates in sputum smear (52.0% vs. 34.3%; P = 0.003), sputum culture (69.7% vs. 56.9%; P = 0.032), Xpert MTB/RIF (66.3% vs. 51.2%; P = 0.013) and TB-DNA (51.5% vs. 31.2%; P = 0.001) than those in Group TB1. Patients in Group TB2 had higher incidence in cough (78.8% vs. 62.3%; P = 0.004), expectoration (64.4% vs. 45.1%; P = 0.001), concomitant extrapulmonary TB (14.1% vs. 5.9%; P = 0.016), cavities (47.9% vs. 34.0%; P = 0.022), and unfavorable outcomes after anti-TB treatment.ConclusionThe clinical, laboratory and radiological manifestations of TB patients with high plasma sCD25 levels indicate that the disease is more severe. Tracking plasma sCD25 detection of TB patients has evident clinical significance. It is noteworthy that when the plasma sCD25 levels are significantly elevated, patients should be cautious of the TB progression and disease severity.

Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection.

Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV+, TPV+ versus TPV- exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhigh monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

Serum soluble toll-like receptor 4 and risk for clinical severity in COVID-19 patients

Toll-like receptor 4 (TLR4) signaling mediates sustained systemic inflammation in(COVID)-19 patients. We aimed to assess the serum levels of sTLR4 and sCD14 as negative regulators of Toll like receptor signaling and their association with laboratory markers and clinical severity in covid 19 patients. Ninety-eight patients with COVID-19 (70 severe and 28 non-severe) were enrolled in the study. Serum sCD14 andsTLR4were determined by ELISA. A significant increase in serum sTLR4 and sCD14 levels was detected in severe compared to non severe COVID19 patients.Receiver operating characteristic curve (ROC) analysis revealed significant diagnostic potential of serum sTLR4 and sCD14 in covid19 patients.We conclude that Serum sTLR4 and sCD14 may be promising clinical severity markers for COVID19 patients.

The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes.

Although the contribution of enhanced glial activity in seizure induction is increasingly recognized, the role of glia-induced neuroinflammation in the physiopathology of epileptic encephalopathy (EE) has been scarcely investigated. To delineate the contribution of glial activity in EE, we measured levels of glia-derived mediators with previously described biomarker value, including glial fibrillary acidic protein (GFAP), high mobility group box 1 (HMGB1), chitinase-3-like protein 1 (CHI3L1), soluble CD163 (sCD163) and triggering receptor expressed on myeloid cells 2 (TREM2) by ELISA in sera of patients with idiopathic West syndrome (WS, n=18), idiopathic Lennox-Gastaut syndrome (LGS, n=13) and healthy controls (n=31). Patients with EE showed significantly higher CHI3L1 levels compared to healthy controls. Levels of HMGB1, CHI3L1, sCD163 and TREM2 were higher in LGS patients than WS patients and/or healthy controls. One or more of the investigated mediators were associated with treatment responsiveness, disease severity and presence of pathological features on electroencephalography (EEG). To our knowledge, our findings provide the initial patient-based evidence that astrocyte- and microglia-mediated neuroinflammation might be involved in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic EE.

The beneficial effect of probiotics as an adjuvant treatment in childhood drug resistant epilepsy: A prospective pilot study.

One of the most common long-term neurological disorders affecting children is epilepsy. Even with effective antiseizure medications, one-third of epileptic patients develop drug-resistant epilepsy (DRE). Numerous treatments have been offered to these DRE patients, though with varying degrees of effectiveness. This study aimed to evaluate the effectiveness of probiotics in improving the quality of life (QoL) and lowering the severity and frequency of epileptic episodes in DRE patients. As well as to assess the anti-inflammatory effects of probiotics. DRE patients were daily supplemented with one probiotic for 4months. During these 4months, patients continued their routine anti-epileptics with no change in the doses. Before and following the 4-month trial, patients had their QoL evaluated using the validated Arabic version of QoL in epilepsy-31 inventory (QoLIE-31) questionnaire, an electroencephalogram (EEG) examination, and serum soluble CD14 (sCD14) evaluation by ELISA. Of the 21 DRE patients who completed the study, 42.9% achieved the therapeutic goal, which was a ≥50% reduction in seizures. After probiotic, there was a significant increase in time elapsed since the last seizure (p = 0.001) and a decrease in seizure duration (p = 0.038), frequency (p = 0.002), and severity by Chalfont Seizure Severity Score (p < 0.001), as compared to pre-probiotic data. Moreover, there was a significant decrease in serum levels of sCD14 (p < 0.001) and a significant improvement in QoL (p < 0.05). Probiotics may be used as a DRE adjuvant treatment. They can lessen the number and severity of seizures, alleviate the associated inflammation, and enhance the QoL for DRE patients.

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy.

Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Dysbiosis of gut microbiota and metabolites during AIDS: implications for CD4 + T cell reduction and immune activation.

Identifying the gut microbiota associated with host immunity in the AIDS stage. We performed a cross-sectional study. We recruited people with HIV (PWH) in the AIDS or non-AIDS stage and evaluated their gut microbiota and metabolites by using 16S ribosomal RNA (rRNA) sequencing and liquid chromatography-mass spectrometry (LC-MS). Machine learning models were used to analyze the correlations between key bacteria and CD4 + T cell count, CD4 + T cell activation, bacterial translocation, gut metabolites, and KEGG functional pathways. We recruited 114 PWH in the AIDS stage and 203 PWH in the non-AIDS stage. The α-diversity of gut microbiota was downregulated in the AIDS stage ( P < 0.05). Several machine learning models could be used to identify key gut microbiota associated with AIDS, including the logistic regression model with area under the curve (AUC), sensitivity, specificity, and Brier scores of 0.854, 0.813, 0.813, and 0.160, respectively. The decreased key bacteria ASV1 ( Bacteroides sp.), ASV8 ( Fusobacterium sp.), ASV30 ( Roseburia sp.), ASV37 ( Bacteroides sp.), and ASV41 ( Lactobacillus sp.) in the AIDS stage were positively correlated with the CD4 + T cell count, the EndoCAb IgM level, 4-hydroxyphenylpyruvic acid abundance, and the predicted cell growth pathway, and negatively correlated with the CD3 + CD4 + CD38 + HLA-DR + T cell count and the sCD14 level. Machine learning has the potential to recognize key gut microbiota related to AIDS. The key five bacteria in the AIDS stage and their metabolites might be related to CD4 + T cell reduction and immune activation.

Assessment of Serum Soluble CD30 Levels in Pediatric Kidney Transplant Recipients

BACKGROUND: CD30 is considered to be a marker for the activated immune system; however, its association with acute rejection and kidney graft function showed severe heterogeneity. AIM: The aim of this study is to examine the predictive value of soluble CD30 (sCD30) levels for kidney transplantation (KT) outcomes in children. MATERIALS AND METHODS: CD30 in serum was measured by ELISA technique in 50 pediatric kidney transplant recipients (KTRs) within 13.4 ± 4.5 days before and within 19.5 ± 9.2 days after KT. sCD30 values were correlated with clinical, laboratory, and immunosuppressive (IS) therapy data and graft function of included patients. Twenty age/gender-matched healthy controls participated as reference values for sCD30 levels. RESULTS: Our study revealed that serum levels of CD30 showed a significant relation between serum sCD30 levels: Pre/post-transplantation (p = 0.02) with increasing sCD30 levels after transplantation (71.60 pg/mL vs. 90.20 pg/mL). In the time, there were no relations between sCD30 with other parameters. CONCLUSIONS: Our results suggest that the measurement of serums CD30 levels may be used as a valuable biomarker in renal transplantation when it is measured pre/post-transplantation.

CD27-Armored BCMA-CAR T Cell (CBG-002) Therapy for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial

Introduction: Several BCMA CAR T-cell products have been approved for relapsed or refractory multiple myeloma (RRMM), but long-term response has not been established. There is growing interest in the use of next-generation CAR T-cell therapy in RRMM. CBG002 is an armored BCMA CAR T-cell product engineered to constitutively express CD27, which binds CD70 to promote T-cell proliferation and differentiation. In vitro, CBG-002 cells exhibited enhanced proliferation, greater cytotoxicity and a higher proportion of memory T cells compared to control BCMA-CAR T cells; in animal models, CBG-002 infusion also resulted in improved tumor control and prolonged survival in MM xenograft mice. Based on the preclinical data, we conducted a phase I clinical trial to evaluate its safety and efficacy in patients with RRMM. Methods: This is a single-arm, open-label, phase I study (NCT04706936). Key eligibility criteria were RRMM patients who had received at least 3 prior regimens, including a proteasome inhibitor and an immunomodulatory drug; the percentage of BCMA expression ≥50% on myeloma cells, detected by either flow cytometry and immunohistochemistry. Patients received 3 days of fludarabine (30 mg/m 2) and cyclophosphamide (300 mg/m 2) followed by a single dose of CBG-002 infusion. The dose-escalation study follows a “3+3” design with 1×10 6/kg, 2×10 6/kg and 3×10 6/kg CAR-T cell cohorts. The primary endpoint was safety, including grade 3 or 4 treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs); The secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: As of June 25, 2023, 12 patients were enrolled and 1 patient was later excluded due to &amp;lt;50% BCMA expression. Among the evaluable 11 patients, there were 9 males and 2 females; median age was 52 years (range 36-66), 5/11 (45.5%) patients had high-risk cytogenetics including complex karyotype, t(4;14),1q21 amplification and del(17p), 4 (36.4%) had extramedullary disease (EMD). The median number of prior treatments was 5 (range 3-7); 7/11 pts were triple-agent exposed and refractory; 5/11 underwent ASCT. The most common TEAEs were neutropenia (G3/4 63.6%), thrombocytopenia (G3/4 36.4%) and anemia (G3/4 45.5%). Nine patients developed G1/2 CRS, which resolved spontaneously except for 2 patients who required steroids and tocilizumab, and no patients developed G3/4 CRS or ICANS. The median time to onset of CRS was 7 days (range 5-21) and the median duration was 6 days (range 5-8). At a median follow-up of 9 months, the ORR was 81.8%, including sCR/CR of 63.6%, VGPR 9.1% and PR 9.1%. After infusion, 8 pts were MRD negative in bone marrow by flow cytometry at day 28, 5 pts continued at month 3. The median OS was 14 months and the OS rate was 100%. The median PFS was 9 months and the PFS rate was 60%. The CBG-002 kinetics paralleled peripheral blood sCD27 levels with a median time to peak of 15 days (range 7-14). The fold increase in sCD27 levels was significantly higher in responders (12.1, range 1.2-83.8) than in non-responders (1.68, range 0.81-9.45). Conclusions: In this phase I study, CBG-002, a CD27-armored BCMA-CAR T therapy has demonstrated remarkable safety and clinical activity in RRMM patients.

Soluble CD163; A Possible New Biomarker in Multiple Myeloma

INTRODUCTION Tumor associated macrophages (TAM) constitute a major part of the bone marrow microenvironment and play a pivotal role in growth of various hematologic malignancies, such as Multiple Myeloma (MM). Cytokines secreted by TAM, such as hemoglobin scavenger receptor CD163, can be detected in their soluble form (sCD163) and reflect the TAM burden. It was recently published that bone marrow TAMs protect neoplastic plasmacytes from chemotherapy-based apoptosis. In our study, we aimed to investigate the clinical utility of sCD163 in patients with Multiple Myeloma. PATIENTS AND METHODS One hundred and nineteen patients were included in the study of whom 80 had symptomatic MM, 30 appeared to have SMM and 8 had MGUS. Clinical and laboratory characteristics were reviewed, after patients' informed consent form. Their median age was 68 yrs (range, 30-89), 53% were men and 47%women; 39%, 27%, and 35% of MM patients were staged ISS1, ISS2 and ISS3 respectively. Serum sCD163 was tested in frozen sera collected at patients' diagnosis and in 30 healthy individuals (HI) . Measurements were performed by ELISA (Duo-Set R&amp;D Quantiquine) according to the manufacturer's instructions. Median value of variables was used as the cut off point. Median time to treatment (TTT) was 0 months (range,0-248) in MM patients and median overall survival (OS) was 67 months (range, 0-248). Statistical analysis was performed with the SPSS v.26 software. RESULTS Median sCD163 was 26618 pg/ml (11831- 35548) in HI, 24366 pg/ml (13166 - 27429) in MGUS, 27665 (18266-39088) pg/ml in SMM, and 27870 (20720-37478) pg/ml in MM patients.Significantly lower levels of CD163 were observed between MGUS and HI (p=0.001) and HI and MM patients (p=0.015). Shorter time to treatment was observed in all MM patients including SMM with sCD163 levels above median (p = 0.034). Patients who became symptomatic after 6 months of diagnosis were studied separately, with levels above the median indicating a shorter time to therapy (p=0.003). Also, a trend of shorter overall survival was observed in all patients (MM, SMM, MGUS) with levels of CD163 above median (p=0.07). CONCLUSION Our findings reveal that serum sCD163 levels differed in patients with MGUS, SMM, MM, and HI, and could predict TTT in MM, indicating that cells of the monocyte-macrophage lineage may play a role in disease pathophysiology and progression. sCD163 could eventually prove to be a significant prognostic factor in MM.

High IL1-RA Plasma Levels at Baseline Allow to Identify Hodgkin Lymphoma Patients with High Risk of Treatment Failure

Introduction: About 10% of localized stages and 20-30% of advanced stages patients (pts) with classical Hodgkin lymphoma (cHL) progress or relapse after the first line of treatment. Therapeutic failures prediction at diagnosis is a major challenge to modulate treatments to minimize acute and long-term toxicities, while having optimal efficacy. The development of prognostic tools is crucial to help therapeutic decision. In 2007, Casasnovas et al. JCO 2007, demonstrated that a plasma cytokine signature composed of IL1-RA, IL-6 and sCD30 could predict pts outcomes and identify pts with high risk of treatment failure. However, it was unusable in routine practice as the ELISA technique used had extensive delay. Since interim PET during induction chemotherapy became the standard approach to guide the therapeutic strategy, and therefore the use of new pre-therapeutic biomarkers deserves to be investigated in the context of PET-guided treatment. As PD-L1, and thymus and activation-related chemokine (TARC) have an important role in cHL physiopathology we analyzed the prognostic impact on progression-free, and overall survival (PFS and OS) of pretherapeutic plasma levels of PD-L1 and TARC in addition to IL1-RA, IL-6, sCD30, in pts treated with a PET-guided strategy. Method: The dosage of IL1-RA, IL-6, PD-L1 and TARC was performed using the ELLA automated immunoassay system (Biotechne) while sCD30 was performed in triplicate using ELISA assay. Samples were prospectively collected (period 2016-2020) within the biocollection BIO-LYMPH (NCT04417803) in the pts treated in the department of Hematology at Dijon Hospital. X tile analysis was used to define the optimal cutoff for survival prediction for each cytokine. Survival functions of pts' subgroups defined by the cytokine circulating levels were estimated using the Kaplan-Meier product limit method and compared using the log rank test. The Cox proportional hazard regression model was used to estimate HRs and associated 95% CI in univariate and multivariate analyses. Results: Among the 105 pts enrolled in this study (Median age: 36 years, range: 17 - 85), 60% were under 45 years, 61% had advanced stage disease, 58% B symptoms, and 39% an IPS &amp;gt;2. 63% of pts had nodular sclerosis HL subtype and 22% had EBV associated HL. Response was assessed at the end of treatment: 89 pts (84 %) achieved a complete response, 4 pts (4%) a partial response, and 9 pts (9%) had progressive disease. With a median follow-up time of 40 months (1-78 months), 13 pts (12 %) relapsed with a median time to relapse of 16 months (range, 4 to 65 months), 14 pts (13 %) died (11 due to cHL progression; 1 due to septic shock; 1 from SARS covid infection; and 1 after a traumatism). While pretherapeutic plasmatic levels of IL-6, sCD30, TARC and PD-L1 did not impact pts survival, IL1-RA was an independent predictor of both PFS and OS. Indeed, 31% of pts harbored high IL1-RA plasma level (≥ 740 pg/ml) and had an unfavorable PFS (5y-PFS: 50.2% vs 86.7%; HR=4.2, CI=2.1-10.3, p=0.0001, figure 1A) and OS (5y-OS 71.4% vs 95%, HR=4.49, CI=1.3-14.2, p=0.006). PET2 positivity (17% of pts) had an unfavorable prognosis value on PFS (5y-PFS 58% vs 86.6%, HR 4.3, CI= 1.4-12.8, p=0.014) but not on OS (5y-OS 91.8% vs 74.1%; HR=3.2 CI=0.7-14.4, p=0.15) independent from pretherapeutic IL1-RA plasma level (PFS multivariate analysis: PET2 positivity HR=2.43, CI=1-6, p= 0.05; High level IL1-RA HR= 3.4, CI=1.5-8.3, p= 0.005). The combination of both PET2 results and pretherapeutic IL1-RA plasma levels allow to stratify pts' outcome into 3 groups (figure 1B): - Pts (57%) with low levels of IL1-RA and negative PET2 had a 5y-PFS of 89.3% and 5y-OS of 95.8%, - Pts with high levels of IL1-RA or positive PET2 (35%) had a 5y-PFS of 57% and 5y-OS of 74.8% whereas - Pts with both (8%) had a 5y-PFS of 42.9% and 5y-OS of 71.4%. The groups with one or 2 prognostic factors (PET2+ or high IL1RA and PET2+ &amp; high IL1RA) had a significantly different PFS compared to the double negative group (1 factor: HR=4.7, CI=1.8-12.2, p=0.0011 and 2 factors: HR= 8.57, CI=2.5-28.3, p=0.0004 respectively). The group with 1 prognosis factor had a significantly different OS (HR=4.1, CI=1.1-15.3, p=0.03) compared to double negative group but not the 2 factors group (HR= 4.9, CI=0.8-30, p=0.08). Conclusion: Pretherapeutic IL1-RA plasma levels allow to stratify the prognosis of pts with cHL treated with first line PET-guided strategies and add prognosis information to PET2 response.

Myelodysplastic Syndrome Associated Hemophagocytic Lymphohistiocytosis: A Retrospective Study of 15 Cases in a Single Center

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by excessive cytokine secretion, resulting in hyperinflammation and multiorgan dysfunction. It is classified into primary HLH, which is mainly caused by genetic defects, and secondary HLH, triggered by various underlying conditions. Malignancy-associated HLH (M-HLH) is a secondary form commonly observed in patients with hematological malignancies, such as lymphomas, T/NK-cell disorders, acute leukemias, lymphoproliferative diseases, and myelodysplastic syndrome (MDS). M-HLH can occur in up to 1% of patients with hematologic malignancies, with lymphoma being the most frequently associated malignancy. HLH initiated by MDS is a rare entity with only a few cases reported, leading to limited knowledge regarding its pathogenesis, diagnosis and optimal treatment strategies. Methods: In this retrospective study, we analyzed a consecutive series of MDS-HLH patients admitted to our center between March 1, 2019, and March 1, 2023. Bio-clinical data related with MDS and HLH were collected at diagnosis of MDS-HLH. Additional observational indicators encompassed the following: basic clinical characteristics of the patients (age at onset, gender, duration of MDS prior to HLH), correlation between the onset of HLH and MDS, treatment and response, and genetic defects associated with HLH and MDS. MDS risk classification was according to the Revised International Prognosis Scoring System (IPSS-R) and the WHO classification-based Prognosis Scoring System, while patients were categorized into two groups as higher-risk and lower-risk MDS-HLH group. The follow-up period started at the time of MDS-HLH diagnosis and ended at the date of death or last examination. Overall survival (OS) was calculated from the time of HLH diagnosis to the date of death from any cause. Results: A total of 15 patients diagnosed with MDS-HLH were included in the study, with a median age of 66 years (range, 33-83 years). The majority of patients (10/15, 67%) were over 60 years old. All patients exhibited typical features of aggressive HLH: fever, cytopenia and elevated serum ferritin in all patients, hepatomegaly/splenomegaly in 87% (13/15), hypofibrinogenemia/hypertriglyceridemia in 73% (11/15), hemophagocytosis in 73% (11/15), low NK-cell activity in 21% (3/14), and elevated levels of sCD25 in 93% of patients (14/15). Additionally, four patients (27%) had concurrent Epstein-Barr virus (EBV) infection. Further analysis comparing the lower-risk and higher-risk MDS-HLH groups revealed interesting findings. In the lower-risk group, all patients developed HLH concurrently with the diagnosis of MDS. However, in the higher-risk group, the majority of patients (6/8, 62.5%) experienced HLH onset during MDS progression or relapse (p=0.014). Among the 15 patients, 8 patients (53.3%) achieved remission of HLH. During the study period, 8 deaths occurred, all directly attributed to HLH or its complications. The majority of deaths (75%, 6/8) occurred within the first two months after HLH diagnosis. The median overall survival was 12.3 weeks (95%CI, 1.1-23.5). Patients who achieved complete or partial response had significantly prolonged overall survival compared to those who did not respond to treatment (p=0.002). In the multivariate analysis of prognosis, the remission status of HLH was the only factor which was significantly associated with survival (p=0.018, Exp(B)=0.003). Conclusion: This is the first comprehensive study focusing specifically on MDS-HLH, providing valuable insights into the clinical characteristics, treatment outcomes, and prognosis of MDS-HLH. The findings emphasize the need of considering revision of diagnostic criteria specially for MDS-HLH. The pathogenesis of HLH in MDS-HLH differs based on the risk classification of MDS, with higher-risk cases driven by malignancy and lower-risk cases associated with immune dysfunction. The prognosis of MDS-HLH is generally poor. Achieving remission of HLH is crucial for improving the prognosis of MDS-HLH patients. Conventional chemotherapy regimens, including etoposide, have shown limited efficacy and safety in this context. Chemotherapy-free regimens should be preferred considering the features of ineffective hematopoiesis in MDS. The role of EBV infection in MDS-HLH development should be recognized.

Effectiveness of rosuvastatin and pulmonary rehabilitation in patients with concurrent course of asthma, chronic obstructive pulmonary disease and diabetes mellitus type 2

The aim of this study was to assess the effectiveness of rosuvastatin and pulmonary rehabilitation in patients with asthma-COPD overlap (ACO) concurrent with type 2 diabetes (T2D).Material and methods. A total of 26 patients with ACO and T2D were examined, with an average age of 61 [55.6; 67.8]. In addition to standard therapy, patients in the main group were prescribed rosuvastatin and a pulmonary rehabilitation program. Treatment efficacy was assessed using questionnaires (CAT, ACQ, SGRQ), dyspnea severity scale (mMRC), BODE index, pulmonary function, bioimpedance analysis, 6-minute walk test, carbohydrate and lipid metabolism status, levels of 8-isoprostane, sCD14, CRP, stable nitric oxide (NO) metabolites - nitrite and nitrate ions, and endothelin-1 in the blood. Results. In the main group, a significant improvement was observed during the treatment course, including a 40% reduction in the BODE index (p&lt;0.05), a 33.4% decrease in dyspnea on the mMRC scale (p&lt;0.05), a 28.5% reduction in CAT, a 40.8% decrease in ACQ, and a 20.6% decrease in SGRQ. Other notable improvements included a 1.3% decrease in BMI, a 13% reduction in body fat percentage, a 23.5% decrease in visceral fat level, a 16% increase in patients' tolerance to physical activity, a 27.5% increase in FEV1 (p&lt;0.05), an 8.1% decrease in fasting blood glucose (p&lt;0.01), a 20% reduction in triglycerides (p&lt;0.05), a 24.9% decrease in LDL cholesterol, and a 27.2% decrease in total cholesterol (p&lt;0.05). Additionally, there was a 23.8% decrease in CRP levels (p&lt;0.05), a two-fold reduction in blood 8-isoprostane levels (p&lt;0.05), a 58% reduction in serum sCD14 levels, a 59.8% increase in stable nitric oxide metabolites (p&lt;0.05), and a 55% decrease in endothelin-1 levels (p&lt;0.05).Conclusions. The use of rosuvastatin and pulmonary rehabilitation significantly improves the quality of life for patients with the concurrent presentation of COPD, asthma, and T2D. It reduces the severity of dyspnea, enhances tolerance to physical activity, improves pulmonary function, lowers visceral fat levels and body fat percentage, enhances lipid profile, and improves endothelial function, all while concurrently reducing oxidative stress and systemic inflammation without worsening carbohydrate metabolism.

Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance.

Combination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa. We conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation. A group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3-230.2)] in women who had CD4+ T-lymphocyte counts <350 cells/µL compared with those with ≥350 cells/µL [21.1 µg/g (0-58.4)], p = 0.032. Plasma sCD14 levels were significantly higher in the HIV-infected group at both 6 weeks and 6 months postpartum, p < 0.001. Plasma LBP levels were similar, but higher levels were observed in HIV-infected women with elevated fecal calprotectin. We found significant correlations between fecal calprotectin, LBP, and sCD14 with proinflammatory cytokines. Gut microbial alpha diversity was not affected by HIV status and was not affected by use of antibiotic prophylaxis. HIV significantly affected microbial beta diversity, and significant differences in microbial composition were noted. The genera Slackia and Collinsella were relatively more abundant in the HIV-infected group, whereas a lower relative abundance of Clostriduim sensu_stricto_1 was observed. Our study also found correlations between gut microbial taxa abundance and systemic inflammatory biomarkers. HIV-infected lactating women had increased immune activation and increased microbial translocation associated with increased gut inflammation. We identified correlations between the gut inflammation and microbial composition, microbial translocation, and systemic inflammation. The interplay of these parameters might affect the health of this vulnerable population.

Circulating levels of FoxP3, M2 (sCD163) and IGF-1 as potential biomarkers associated with Laryngeal Squamous Cell Carcinoma in Tunisian patients

ABSTRACT We aim to assess the clinical impact of circulating levels of sCD163, FoxP3, IGF-1 in LSCC patients (Laryngeal Squamous Cell Carcinoma). The concentrations of sCD163, FoxP3, and IGF-1 were measured using ELISA test in the serum samples collected from 70 pretreatment LSCC patients and 70 age and sex-matched healthy controls. Statistical analysis was performed using ANOVA to compare the two groups, and the correlation between markers and clinical parameters. Receiver-Operator Characteristic (ROC) curve analysis was conducted to determine the optimal cutoff values and evaluate the diagnostic impact of these markers. Significant differences in the levels of sCD163, FoxP3, and IGF-1 were observed between LSCC patients and the control group, with respective p-values of 0.01, 0.022, <0.0001. The determined cutoff values for sCD163, FoxP3, IGF-1 concentrations were 314.55 ng/mL, 1.69 ng/mL, and 1.69 ng/mL, respectively. The corresponding area under the curve (AUC) values were 0.67 (95% CI: 0.57–0.76), 0.70 (95% CI: 0.61–0.80), 0.84 (95% CI: 0.76–0.92), respectively. Furthermore, it was found that IGF-1 concentrations exceeding 125.20 ng/mL were positively correlated with lymph node metastasis. Elevated serum levels of sCD163, FoxP3 and IGF-1 are associated with the diagnosis of LSCC. IGF-1 appears to be the most promising indicator for the LSCC progression.

Effects of Jujube Powder on Growth Performance, Blood Biochemical Indices, and Intestinal Microbiota of Broiler.

In total, 576 Cobb broilers were randomized into 6 treatment groups, with 8 replicates in each treatment group and 12 broilers in each replicate. Each treatment group was fed six different experimental diets containing 0%, 2%, 4%, 6%, 8%, and 10% jujube powder. The group receiving 0% jujube powder was considered the blank control group. The experimental period was 42 days and was divided into two periods: starter (0-21 days) and finisher (22-42 days). Compared with the control group, the addition of 8% jujube powder significantly improved the ADG of broilers (p < 0.05), and 8% and 10% jujube powder significantly improved the total tract apparent digestibility of organic matter in broilers (p < 0.05). Adding 10% jujube powder significantly improved the apparent metabolic energy of broilers (p < 0.05). Compared with the control group, 4-10% jujube powder significantly increased IgA, IgG, IgM, and sCD4 levels (p < 0.05) and T-AOC and SOD contents, and it reduced the MDA content in the serum of broilers (p < 0.05). In addition, the relative abundance of Firmicutes, Bacteroidetes, Lactobacillus, and Romboutsia significantly increased in the broiler ileum, whereas that of Proteobacteria and Enterobacter decreased significantly (p < 0.05) when 8% jujube powder was added to the diet. The relative abundance of Proteobacteria, Bacteroides, and Faecalibacterium in the cecum increased significantly (p < 0.05), whereas that of Bacteroidetes decreased significantly (p < 0.05).