sIL-2R Levels Research Articles

In Vitro Anti-inflammatory Effect of Secretome from Umbilical Cord-derived Mesenchymal Stem Cells in COVID-19 Patient Blood: A Study on sIL-6R, sgp130, IL-1RA and Anti/pro Inflammatory Cytokines

COVID-19 exhibits a wide range of clinical manifestations which severity of the disease is linked to uncontrolled escalation of inflammatory mediators. Ongoing research has identified the immunomodulatory effects of the MSC-derived secretome as a potential therapy for COVID-19. However, the precise mechanism by which the secretome exerts its therapeutic effect on COVID-19 remains unclear. This study aims to investigate whether the components of the UC-MSC-derived secretome can alter the inflammatory characteristics of immune cells. To achieve this, an in vitro study will be conducted involving co-incubation of whole blood with secretomes, followed by LPS stimulation. A total of 12 blood samples from severe COVID-19 and healthy subjects were cultured into three groups (RPMI control, 3μl and 9μl secretome group) incubated for 24 hours. Then, the cultures were exposed to LPS for 48 hours. The levels of sIL-6R, sgp130, IL-1RA, IL-6, TNF-α, IFN-γ, and IL-10 were measured. Results showed that LPS increased IL-6, TNF-α, and IL-10 production, while reducing sIL-6R, and sgp130, but no changes seen in IFN-γ in secretome-incubated blood cultures. The post-LPS/pre-LPS ratio analysis was conducted to investigate the anti-inflammatory potential of secretome. It was found that the secretome provides its anti-inflammatory effects through the role of IL-1RA.

Non-linear relationship between soluble interleukin-2 receptor and prognosis of diffuse large B-cell lymphoma.

Despite an emphasis on the prognostic impact of serum soluble interleukin-2 receptor (sIL-2R) at diagnosis in patients with diffuse large B-cell lymphoma (DLBCL), whether the prognostic impact of elevated sIL-2R is linear remains unclear. To verify the presence of a non-linear association between sIL-2R level at diagnosis and overall survival (OS) in patients with newly diagnosed DLBCL, we conducted a multi-center, observational retrospective study. Among 488 analyzable patients, Cox proportional hazards modeling identified serum sIL-2R level at diagnosis as an independent predictor of OS. Multivariate Cox hazard modeling with restricted cubic spline model demonstrated that the relationship between serum sIL-2R level and OS was clearly non-linear (P for effect of sIL-2R = 0.002; P for non-linearity = 0.015). Mortality risk increased gradually as sIL-2R levels increased and plateaued at approximately 5,000 U/mL. Segmented regression analysis revealed that the trend in negative prognostic impact from a gradual increase in serum sIL-2R level changed significantly, with a breakpoint at approximately 2,000 U/mL. Multivariate receiver operating characteristic curves showed a significant improvement in prediction ability when serum sIL-2R level was added to the International Prognostic Index (IPI). Serum sIL-2R level at diagnosis was not only a prognostic factor, but also improved predictive accuracy for OS when incorporated with the IPI. However, the negative correlation between increasing sIL-2R and prognosis was non-linear.

Diagnostic Value of sLR11 and sIL-2R in the Cerebrospinal Fluid for Malignant Central Nervous System Lymphoma.

Objective We previously reported that patients with acute leukemia and malignant lymphoma (ML) demonstrated significantly increased serum soluble LR11 (sLR11) levels compared to normal controls. Accurately diagnosing ML of the central nervous system (CNS ML) using cytology is frequently difficult. Therefore, we evaluated the use of cerebrospinal fluid (CSF) sLR11 and soluble interleukin-2 receptor (sIL-2R) as diagnostic and treatment response markers for CNS ML. Methods We retrospectively evaluated the CSF results for CNS ML using clinical data at our institution, and then analyzed the usefulness of sLR11 and sIL-2R in CSF for both the diagnosis and as surrogate markers that reflect the therapeutic effect. Patients We enrolled patients with CNS ML who received intrathecal anticancer drugs between 2017 and 2023. We analyzed the sLR11 and sIL-2R levels in CSF and cytological malignant grades. We studied 22 patients, including 17 with central nervous system (CNS) clinical conditions and five who received prevention treatment. Results The CSF sLR11 levels were significantly and positively correlated with CSF sIL-2R levels. The CSF sLR11 and sIL-2R levels in patients with CNS ML were significantly higher than those in the prevention group. A receiver operating characteristic (ROC) curve analysis showed the cut-off value of sLR11 for CNS invasion to be 21.7 ng/mL. Moreover, the chemotherapy-responder group demonstrated significantly decreased CSF sLR11 and sIL-2R levels after treatment. Conclusion CSF sLR11 and sIL-2R of CSF were found to be useful biomarkers for the diagnostic and treatment response evaluation in patients with CNS ML.

Diagnostic challenge: Combination of magnetic resonance imaging and serum soluble Interleukin-2 receptor in soft tissue non-hodgkin lymphoma

PurposeNon-Hodgkin lymphoma (NHL) sometimes occurs in soft tissue (referred to as soft tissue lymphoma or soft tissue NHL), often mimicking soft tissue tumors. Despite some clinical indicators, accurate diagnosis of soft tissue NHL before biopsy remains challenging. We investigated the diagnostic value of serum soluble interleukin-2 receptor (sIL-2R) levels and magnetic resonance imaging (MRI) as an initial tool to assess the likelihood of soft tissue NHL. MethodsWe analyzed 36 cases of pathologically proven soft tissue NHL initially suspected as soft tissue tumors alongside 48 control cases of soft tissue sarcoma or carcinoma. Patient medical charts and MRI scans were retrospectively reviewed and statistically analyzed, focusing on assessing the diagnostic efficacy of soft tissue NHL. ResultsThe diagnostic accuracy of soft tissue NHL combining the appearance of homogeneity on MRI (T2-weighted and/or short-time inversion recovery [STIR] images) and sIL-2R value (≧ 904 U/mL) yielded a sensitivity of 78 % and 86 %, and specificity of 83 % and 88 %, respectively. Meeting one or both criteria increased the sensitivity to a maximum of 92 %, albeit with a specificity of 71 %. When both criteria were met, sensitivity and specificity were 72 % and 100 %, respectively. ConclusionThe integrated approach of combining MRI and sIL-2R demonstrated excellent efficacy in predicting the diagnosis of soft tissue NHL, which was initially referred to as soft tissue tumor.

Systemic Inflammation In Asymptomatic Hyperuricemia With Sonographic Crystal Deposits, Including A Comparison With Normouricemia And Gout.

To describe the inflammatory profile of asymptomatic hyperuricemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout, and normouricemia. Based on serum urate levels, musculoskeletal ultrasound, and history of flares, we divided 122 participants into four groups: normouricemia, AH-MSUneg, AH-MSUpos, and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2-3 (G2-3) double contour and/or tophi, G1-3 double contour and/or tophi, G1-3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint), and G2-3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates, and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricemics. Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-β, and galectin-3 were higher in hyperuricemics vs normouricemics. Sex, obesity, and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUpos vs AH-MSUneg groups, except for higher calprotectin using G1-3 sonographic definitions and higher CRP and TGF-β when restricted to women and obese participants. Hyperuricemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-β. Sex, obesity, and comorbidities influenced some inflammatory responses.

A study of the relationship between circulating cytokines (interleukin-2 receptor and tumor necrosis factor receptor 2) and risk of B-cell non-hodgkin lymphoma.

Mature B-cell non-Hodgkin lymphoma (B-NHL) occurs due to uncontrolled B-lymphocyte clonal expansion. Cytokines can directly stimulate B-cell proliferation and prevent B-cell apoptosis. Dysregulation of cytokines may play an important role in the development of B-NHL by enhancing chromosomal translocation, which is the hallmark of B-NHL. Both interleukin 2 and tumor necrosis factor-α are proinflammatory cytokines and play important roles in the growth, differentiation, and apoptosis of B cells.We conducted a prospective case-control study applied to 50 patients with B-NHL at Kasr Al Aini Hospital, Cairo University, and 50 age- and sex-matched controls. Clinical, laboratory and imaging data were collected. In all patients and controls, sIL-2R and sTNF-R2 levels were measured by enzyme-linked immunosorbent assay (ELISA). The Spearman correlation test was used to evaluate the correlation between the studied cytokines and clinical, laboratory and imaging findings. Sensitivity analysis was conducted to detect the cutoff values of the studied cytokines.Serum levels of sIL-2R and sTNF-R2 were significantly higher in patients than in controls. Additionally, their levels were significantly higher in aggressive types and advanced stages of lymphoma. Also, the studied cytokines were significantly correlated with different clinical and laboratory parameters of lymphoma. The level of sIL-2R and sTNF-R2 were closely related to the type of lymphoma (P value ˂ 0.001 and 0.012, respectively), further it was also associated with the natural history of lymphoma (aggressive vs. indolent) (P value ˂0.001 and 0.04 respectively).We concluded that Pretreatment levels of sIL-2R and sTNF-R2 may play a role in the natural history and prognosis of lymphoma. They may be used as a prognostic factor for B-NHL patients and may also help with treatment decisions.

Evaluation serum soluble interleukin 2 receptor with diagnosis and prognosis in canine solid tumour: 34 cases.

The soluble interleukin-2 receptor (sIL-2R) serve as a valuable biomarker for tumors in human patients, as its levels increase during the activation of T lymphocytes in clinical states such as inflammation, infection, and tumor. This study aimed to demonstrate that sIL-2R levels can be also elevated in dogs with tumors and evaluate its applicability as a diagnostic and prognostic factor in canine cancer patients. Serum was collected from 6 healthy dogs and 34 dogs with solid tumors. The concentration of sIL-2R was measured using a commercial enzyme-linked immunosorbent assay kit. The median sIL-2R concentration was significantly higher in dogs with solid masses than in healthy dogs (117.3 vs 68.33 pg/ml, p=0.016). The highest median sIL-2R concentration was found in dogs with malignant tumors, followed by those with benign tumors, and healthy dogs (119.6 vs 93.74 vs 68.33 pg/ml, respectively). In dogs with malignant tumors, the mortality rate was significantly higher in the group with high sIL-2R levels than in the group with low sIL-2R levels. Dogs with solid tumors, particularly those with malignant tumors, had higher concentrations of sIL-2R than healthy dogs. Among dogs with malignant tumors, a correlation between sIL-2R concentration and mortality rate was confirmed. Serum sIL-2R levels may be used to detect malignant tumors and serve as a prognostic factor in dogs with malignant tumors.

Diagnostic value of soluble Interleukin-2 receptor in patients suffering neurosarcoidosis: A systematic review.

Neurosarcoidosis is an inflammatory granulomatous disease. Up to 25% of occult sarcoidosis affecting the nervous system are only detected by autopsy. In addition, in recent years the suspicion arose that the soluble Interleukin-2 Receptor (sIL-2R) might be useful in differentiating between neurosarcoidosis and neurosarcoidosis-like diseases such as neurotuberculosis, multiple sclerosis, or cerebral lymphoma. Therefore, we aimed to systematically review randomized controlled trials (RCT), observational studies, and case-control studies evaluating sIL-2R levels in neurosarcoidosis patients. For this systematic review, a comprehensive literature search of electronic databases including EMBASE, The Web Of Science, The Cochrane Library, MEDLINE, and Google Scholar was conducted. The search was limited to the English language and publication date up to January 08th, 2024. As part of the search strategy conducted, 6 articles met the inclusion criteria. Two independent reviewers extracted the relevant data from each article. In addition, 2 independent reviewers assessed the quality of each study using the Newcastle-Ottawa Scale (NOS). We included 6 studies comprising 98 patients suffering from neurosarcoidosis, 525 non-sarcoidosis patients, and 118 healthy controls. Included studies were published between 2010 and 2023. Cerebrospinal fluid (CSF) sIL-2R levels differed significantly between neurosarcoidosis patients and multiple sclerosis, vasculitis, and healthy controls whereas serum sIL-2R levels did not reveal sufficient discriminative power. sIL-2R index was able to discriminate neurosarcoidosis from neurotuberculosis, bacterial/viral meningitis, and healthy controls. In this systematic review, we found indications that sIL-2R may be a useful biomarker for the diagnosis of neurosarcoidosis. To determine an additional diagnostic value of sIL-2R, large prospective studies are needed that not only examine absolute sIL-2R levels in serum or CSF but also the dynamic changes as well as the implications of renal function on sIL-2R levels.

Blood cytokines as potential predictors of the development of SARS-CoV-2 associated pneumonia in patients with stage II ESSENTIAL hypertension

The search for predictors of the severe course of COVID-19 was relevant both during the pandemic and at the present time. The aim of the study was to analyze the relationship of cytokine levels in patients with EН before SARS-CoV-2 infection with the incidence of coronavirus pneumonia. Materials and methods. From the database of 290 patients with stage II EAG who have been under observation for 8–12 years with annual blood sampling to determine cytokine levels, COVID-19 survivors were selected (mild without pneumonia and moderate to severe, pneumonia CT 1–2, CT-3). Anamnestic levels of IL-1β, IL-1α, IL-1ra, IL-18, IL-18 BP, IL-37, IL-6, sIL-6r, M-CSF, VEGF-A, IL-34 and HMGB1) in the blood serum of patients with stage II EH were analyzed (method ELISA). The analysis of the obtained results was carried out using Stat Soft Statistica 13.5. Results and discussion. Patients with EH and COVID-19 with pneumonia (CT I-II) after SARS-CoV-2 infection 2–6 months before the infectious disease had significantly higher serum levels: IL-1α (p 0.05) and a decrease in IL-37 (p 0.001). During multivariate correlation analysis, a statistically independent relationship between an increase in the incidence of viral pneumonia in patients with stage II EН was confirmed only for IL-37 with a blood level of less than 60.2 pg/ml (regression coefficient — 2.21, standard error — 0.28, t criterion — 6.12, relative risk — 2.52, criterion Walda — 7.92, p = 0.006). When studying circadian rhythms of cytokine content in blood serum in patients of the analyzed groups, calculating the strength of correlations of anamnestic evening IL-37 levels in patients with stage II EР at 19.00–20.00 with the frequency of pneumonia against the background of SARS-CoV-2 infection, it has greater specificity and sensitivity (specificity — 0.75, sensitivity — 0.82) than morning concentrations. Considering that data on circadian rhythms were obtained in a limited number of patients, further monitoring is necessary, which is carried out by our scientific group. It should be noted that patients with essential hypertension are pathogenetically heterogeneous, including in terms of cytokine regulation. The study of this area will make it possible to personalize cytokine phenotypes of the disease and develop new methods for calculating the prognosis of both cardiovascular complications and features of the course of infectious diseases.

Serum Soluble IL-2 Receptors Are Elevated in Febrile Illnesses and Useful for Differentiating Clinically Similar Malignant Lymphomas from Kikuchi Disease: A Cross-Sectional Study.

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120-6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640-1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538-1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

Association of Baseline Serum Soluble Tumour Necrosis Factor Receptor Levels with the Response of Rheumatoid Arthritis to Janus Kinase Inhibitor Therapy.

The aim of this study was to investigate whether cytokines associated with tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 signalling could predict rheumatoid arthritis (RA) clinical remission (CR) with Janus kinase inhibitor (JAKinib) treatment using the Simplified Disease Activity Index (SDAI). Eighty-nine patients with RA treated with JAKinibs were enrolled, and their clinical data were collected retrospectively. CR was defined as an SDAI ≤ 3.3 after 6 months of treatment with JAKinib. The serum samples of 89 patients were analysed for IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (spg130), and soluble TNF receptor- (sTNFR-) I and sTNFR-II titres. There were no significant differences in the baseline clinical parameters between the CR and non-CR groups. Serum levels of IL-6, sIL-6R, and sgp130 were not significantly different; whereas, the serum sTNFR-I and sTNFR-II levels were significantly lower in the CR group. Univariate and multivariate logistic regression analysis showed that the baseline log sTNFR II values (OR: 0.002; p = 0.034) were predictors of CR. Patients with RA can be stratified prior to JAKinib administration using serum sTNFR-I and sTNFR-II levels but not serum IL-6 axis cytokine levels (IL-6, sIL-6R, and sgp130).

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

Objective: To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer. Methods: Seventy patients diagnosed with differentiated thyroid cancer were selected for the study. TSH inhibition therapy was administered to the research group, while thyroxine replacement therapy was provided to the control group during the postoperative management phase. This allowed for a comparative analysis between the two groups. Results: In comparison with the control group, the research group exhibited significant decreases in serum TSH, T3, and T4 levels after treatment, while FT4 and FT3 levels significantly increased (P &lt; 0.05). Additionally, significant decreases in Tg, VEGF, TSGF, CD44V6, and sIL-2R levels were observed in the research group after treatment (P &lt; 0.05). No significant differences were found in pre-treatment thyroid function between the two groups (P &gt; 0.05). Conclusion: The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.

The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%. A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention. The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy. Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

Factors of Interleukin-6 Signaling in COVID-19 Patients with Lung Damage of Varying Degrees: A Pilot Study.

Specific features of IL-6 signal transduction were studied in 89 patients with lung damage of varying degrees during the first COVID-19 pandemic wave. The levels of IL-6 signaling components (IL-6, sIL-6R, and sgp130) and highly sensitive C-reactive protein (hsCRP) were examined in patients with intact lungs (CT-0), mild (CT-1), moderate (CT-2), moderate to severe (CT-3), and severe (CT-4) lung damage. Seventy patients were re-examined 3-7 months after discharge from the hospital. The IL-6 and hsCRP levels increased several times with severing lung damage severity. In patients with CT-3, sIL6-R increased statistically significantly and remained high in CT-4 patients. sgp130 levels were lower in CT-1 and CT-2 patients and higher in CT-3 and CT-4 patients compared to CT-0 patients. We revealed a positive correlation between IL-6 and hsCRP levels in CT-1, CT-2, and CT-3 patients. In CT-3 patients, sIL-6R levels positively correlated with IL-6 concentration. The studied parameters decreased considerably in all patients 3-7 months after discharge. It can be suggested that IL-6 classic-signaling is predominant in CT-1 and CT-2, while trans-signaling prevails in CT-3. Disorders in regulatory mechanisms of IL-6 signaling occur in CT-4, which prevents physiological elimination of IL-6 hyperactivity. The results obtained are preliminary and require a broader study.

Thyroid stimulating immunoglobulin concentration is associated with disease activity and predicts response to treatment with intravenous methylprednisolone in patients with Graves' orbitopathy.

Thyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO. TSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.2 years old) and 25 healthy controls (5 male, 20 female; mean age 39.8 years old). Clinical characteristics and response to treatment were retrospectively retrieved from patient files. Higher sIL-2R levels were observed in GO patients compared to controls (p < 0.001). sIL-2R correlated with fT4 (r = 0.26), TSH (r = -0.40) and TSI (r = 0.21). TSI and sIL-2R concentrations were higher in patients with active compared to inactive GO (p < 0.001 and p < 0.05, respectively). Both TSI and sIL-2R correlated with total clinical activity score (CAS; r = 0.33 and r = 0.28, respectively) and with several individual CAS items. Cut-off levels for predicting active GO were 2.62 IU/L for TSI (AUC = 0.71, sensitivity 69%, specificity 69%) and 428 IU/mL for sIL-2R (AUC = 0.64, sensitivity 62%, specificity 62%). In multivariate testing higher TSI (p < 0.01), higher age (p < 0.001) and longer disease duration (p < 0.01) were associated with disease activity. TSI levels were higher in patients with a poor IVMP response (p = 0.048), while sIL-2R levels did not differ between responders and non-responders. TSI cut-off for predicting IVMP response was 19.4 IU/L (AUC = 0.69, sensitivity 50%, specificity 91%). In multivariate analysis TSI was the only independent predictor of response to IVMP (p < 0.05). High TSI levels are associated with active disease (cut-off 2.62 IU/L) and predict poor response to IVMP treatment (cut-off 19.4 IU/L) in GO. While sIL-2R correlates with disease activity, it is also related to thyroid function, making it less useful as an additional biomarker in GO.

Serum cytokine profiles during engraftment syndrome and acute graft-versus-host disease in adult patients after hematopoietic stem cell transplantation

BackgroundThe underlying biology of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) is not fully elucidated, and the extent of its overlap with acute graft-versus-host disease (aGvHD) remains unclear. In order to establish potential indicator to distinguish ES more accurately, we conducted a retrospective analysis of cytokine levels during HSCT. MethodsA total of 121 consecutive adult patients who underwent HSCT were enrolled in this study. Blood samples for interleukin (IL)-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1β, IL-12p70, interferon (IFN)-γ, IFN-α, tumor necrosis factor alpha (TNF-α) and C-reactive protein CRP were regularly assessed after transplantation and during transplantation related adverse events. Additionally, the balance of naïve, central memory and effector memory of CD4+ and CD8+ was analyzed around 30 and 60 days after stem cell infusion, respectively. ResultsThirty (24.79 %) and 33 (27.27 %) patients were diagnosed with ES and aGvHD, respectively. ES was characterized by a significant increase in level of IL-5, IL-6, IL-8 and sIL-2R, while aGvHD was associated with a significant upregulation of IL-6, IL-5, IL-10 and sIL-2R in the patients from grade I to grade IV. Notably, patients got much higher levels of IL-6, IL-5 and sIL-2R when developed to ES than to aGvHD. Moreover, a pronounced shift from naïve to memory cells, both in CD4+ and CD8+ subsets, was found in ES patients. ConclusionsThese findings suggest that cytokine profiles could serve as potential indicators for detecting and differentiating ES and aGvHD, enabling timely clinical intervention. Prospective clinical trials involving larger, independent patient cohorts are required to validate these observations.

Effect of combination of molnupiravir with clarithromycin on blood biomarkers in patients with mild-to-moderate COVID-19

Background: Molnupiravir is a type of medication used to treat coronavirus disease 2019 (COVID-19). However, no evidence regarding the therapeutic effect of molnupiravir combined with clarithromycin (CAM) on blood biomarkers is available. Methods: Of the 156 rehabilitation patients, 124 patients with mild-to-moderate COVID-19 were treated with molnupiravir. Among these 124 patients, 54 were treated with CAM. The remaining 28 rehabilitation patients were negative for COVID-19. Blood biomarkers were assessed after administration of molnupiravir in patients receiving molnupiravir plus CAM or molnupiravir alone. Results: Among the measured blood biomarkers, lactate dehydrogenase, potassium, white blood cells, C-reacted protein, neutron–lymphocyte ratio, fibrin degradation product, and prothrombin time–international normalized ratio values were significantly higher (P &lt; 0.05) in the molnupiravir alone group than in the molnupiravir plus CAM group, and lymphocytes were significantly lower (P &lt; 0.05) on day 5 after admission. In the molnupiravir plus CAM group, immunoglobulin (Ig) A levels increased and soluble interleukin 2-receptor levels (sIL2R) decreased (P &lt; 0.05) on day 14 after admission. In addition, COVID-19-negative patients had higher IgA levels and lower sIL2R levels compared to infected patients (P &lt; 0.05). The concomitant administration of molnupiravir plus CAM resulted in fewer sequelae after 12 months, and the incidence of venous thromboembolism was significantly reduced (P &lt; 0.05). Conclusion: In patients with mild-to-moderate COVID-19, concomitant administration of molnupiravir plus CAM showed several non-worsening blood biomarkers, elevated immune activity, and reduced post-infection sequelae. Relevance for Patients: After administration of molnupiravir to patients with mild-to-moderate COVID-19, administration of CAM to patients suffering from secondary macrolide-sensitive bacterial infection was compared with administration of molnupiravir alone. D-dimer, IgA, and sIL2R are potential predictive factors of disease severity in critically ill patients with COVID-19.

Effects of a single phosphate-enriched test meal on inflammasome activity and postprandial inflammatory markers in healthy subjects.

The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers. The analysis included 28 participants who received a single dose of either 700mg phosphorus or a placebo with a test meal. At baseline, 4 and 8h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined. While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells. Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon. ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.

A surgical case of anti-coagulant ileus mimicking small-bowel tumors: a case report

BackgroundAnti-coagulant ileus, characterized by intramural hematoma due to excessive anti-coagulant therapy, presents a diagnostic challenge. Although previously considered uncommon, recently, reporting cases of anti-coagulant ileus have become more frequent. Herein, we report a rare surgical case of anti-coagulant ileus mimicking small-bowel tumors.Case presentationA 79-year-old man was admitted to our hospital for fatigue. He had been administered warfarin for 5 months for atrial fibrillation. On admission, the patient exhibited mild epigastric tenderness. Laboratory test results revealed anemia (hemoglobin, 8.4 g/dL); unmeasurably prolonged prothrombin time (PT) with international normalized ratio (INR) > 8; and elevated soluble interleukin 2 receptor (sIL-2R) levels (849 IU/mL; normal range, 122–496 IU/mL). Abdominal plain computed tomography (CT) showed a circumferentially thickened intestinal wall at one site in the jejunum and two in the ileum. After hospitalization, bowel obstruction did not improve with conservative treatment. Suspecting small-bowel tumors such as lymphoma, the patient subsequently underwent open surgery on day 3 after admission. No obvious tumor mass was observed intra-operatively. However, only thickened and hemorrhagic segments were identified at the suspected sites. We performed partial jejunal and ileal resections of 12 and 27 cm, respectively. Histopathology confirmed submucosal congestion, edema, and hemorrhage in each area without tumor components, leading to the final diagnosis of intramural hematoma. The postoperative course was uneventful, and he was discharged on postoperative day 9. No recurrence occurred during the 5-year follow-up period.ConclusionsWe encountered a surgical case of anti-coagulant ileus, which was difficult to differentiate from malignant lymphoma based on CT findings and high sIL-2R levels. The possibility of anti-coagulant ileus should always be considered in patients on long-term anticoagulation medication and bowel obstruction with high PT-INR values.

Durable remission with lenalidomide in a patient with early relapse of adult T-cell leukemia/lymphoma after cord blood transplantation

A 62-year-old woman with adult T-cell leukemia/lymphoma (ATL) received umbilical cord blood transplantation (CBT) in first complete remission. However, relapse of ATL was detected on day 74 post-transplantation, as evidenced by the rapid growth of lymphoma cells in peripheral blood and an increase in soluble interleukin-2 receptor (sIL2R) levels. Discontinuation of immunosuppressant therapy alone did not improve ATL findings, but treatment with lenalidomide caused lymphoma cells to disappear from the peripheral blood and sIL2R levels to return to normal. Pancytopenia was observed as a lenalidomide-associated adverse effect, but lymphocyte counts were not reduced. The patient was judged to be in complete remission based on results of Southern blot analysis and human T-cell leukemia virus 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow). Flow cytometric analysis of peripheral blood and FISH analysis of X and Y chromosomes revealed that the therapeutic effect of lenalidomide was associated with an increase in the number of donor-derived peripheral natural killer cells. ATL relapse was not observed at 13 months into lenalidomide treatment. Our results suggest that lenalidomide is an effective option for the treatment of post-transplant relapsed ATL.