Serum Soluble Interleukin-2 Receptor Research Articles

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.

Relationship of cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 with the progression and prognosis of viral encephalitis in children

To investigate the relationship of cerebrospinal fluid and serum levels of soluble interleukin-2 receptor (SIL-2R), endothelial nitric oxide synthase (eNOS), and cluster of differentiation 93 (CD93) with the progression and prognosis of viral encephalitis (VE) in children. Prospectively, 102 children with VE admitted from January 2021 to January 2024 were selected as the VE group. The patients were divided into a mild subgroup (64 patients) and a severe subgroup (38 patients) according to disease progression. The patients were also divided into a good prognosis subgroup (29 patients) and a poor prognosis subgroup (73 patients) according to prognosis. A control group of 102 children with central nervous system diseases who were examined and found not to have VE during the same period was selected. The factors contributing to the poor prognosis of children with VE and the predictive value of SIL-2R, eNOS, and CD93 in cerebrospinal fluid and serum for the poor prognosis of children with VE were evaluated. Cerebrospinal fluid and serum SIL-2R, eNOS, and CD93 levels were significantly increased in the VE group, severe subgroup, and poor prognosis subgroup (P<0.05). Multivariate logistic regression analysis showed that high SIL-2R, eNOS, and CD93 levels in cerebrospinal fluid and serum were risk factors for poor prognosis in children with VE (P<0.05). Receiver operating characteristic curve analysis showed that the combination of cerebrospinal fluid SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05). Similarly, the combination of serum SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05). The cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 are significantly elevated in children with VE, and they are associated with VE progression and prognosis.

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.

Serum soluble interleukin-2 receptor alpha may predict tubulointerstitial inflammatory cell infiltration and short-term disease progression in immunoglobin A nephropathy.

This study aims to explore the relationship between serum soluble interleukin-2 receptoralpha (sIL-2Rα) levels and histologic features in immunoglobin A nephropathy (IgAN), and evaluate its predicting values on disease progression and remission status. IgAN patients were included retrospectively. Lee classification, Oxford classification and histological scoring were evaluated. Patients' estimated filtration rate (eGFR) and proteinuria remission status were collected during 6-month follow-up. Logistic regression was used to determine the risk factors and predicting value. Receiver operating characteristic (ROC) curve were used to determine the predicting value for outcome. One hundred seventy-two subjects were included in this study. Individuals in moderate-to-severe tubulointerstitial inflammatory cell infiltration group manifested with significantly elevated serum sIL-2Rα levels than those in non-to-mild group. Serum sIL-2Rα levels were positively correlated with infiltration scores. Serum sIL-2Rα was an independent risk factor for moderate-to-severe inflammatory cell infiltration [sIL-2Rα: OR 1.29 (1.015-1.640, p = 0.038)]. ROC curve analysis regarding predictive value for moderate-to-severe inflammatory cell infiltration of sIL-2Rα suggested area under curve was 0.859 (0.801-0.918, p = 0.000) when sIL-2Rα combined with eGFR < 60mL/(min·1.73 m2), 24-h proteinuria excretion > 1.0g, and hemoglobin. It showed good sensitivity (71.6%) and specificity (87.6%). Additionally, sIL-2Rα levels at kidney biopsy were strong predictive factor for kidney function loss 6months after kidney biopsy [OR 4.161 (1.013-17.088, p = 0.048)]. High serum sIL-2Rα was significantly associated with serious inflammatory cell infiltration in IgAN, and it showed strong predictive value for disease prognosis. Serum sIL-2Rα could be a useful noninvasive biomarker to evaluate the extent of histological injury and disease prognosis in IgAN.

Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring

Background Neoplastic cells in hairy cell leukemia (HCL) express the α chain of the interleukin-2 receptor on their surface, which is secreted in large amounts in the serum in a soluble form (sIL-2R). High serum levels of sIL-2R have previously been reported in HCL. Thus, we assessed whether serum sIL-2R levels correlated with tumor burden, represented a prognostic factor, and if they could be used as a tool for disease monitoring. Methods Serum levels of sIL-2R were measured in 59 patients affected by classical HCL followed at the Hematology Unit of Padova University Hospital. To assess whether sIL-2R levels were representative of tumor burden, we evaluated the relationship of pre-therapy sIL-2R levels with other hematologic features such as leukocyte count, the presence of splenomegaly, β-2 microglobulin levels, lactate dehydrogenase (LDH) levels, CD38 expression, the percentages of circulating hairy cells and bone marrow infiltration. In 50 patients we investigated whether post-therapy sIL-2R levels correlated with clinical response and measurable residual disease (MRD) status evaluated by immunohistochemistry according to consensus guidelines. To determine the usefulness of serum sIL-2R levels for disease monitoring, yearly serial sIL-2R levels were measured in 59 patients, including 5 (8.4%) cases in watch &amp; wait phase and 54 (91.6%) with disease remission after therapy with purine analogues. sIL-2R kinetics were correlated with time to cytopenia (TTC) (hemoglobin &amp;lt;100g/L, neutrophils &amp;lt; 1000/µL or platelets &amp;lt;100.000/µL) and time to next treatment (TTNT). Serum sIL-2R levels were measured by enzyme-linked immunosorbent assay. The correlation of sIL-2R levels with other variables was evaluated by linear or logistic regression as appropriate. Medians were compared using the Mann-Whitney U test. Survival and univariate analyses for TTC and TTFT were conducted according to the Kaplan-Meier method and Cox proportional hazards model. Results The mean age of patients was 60.6 years; 10 were females (17%), and 49 were males (83%). Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin. Pre-therapy sIL-2R levels significantly correlated with leukocyte count (r 2 = 0.13; p = 0.009), β-2 microglobulin levels (r 2 = 0.44; p &amp;lt; 0.001), CD38 expression (p = 0.018), the percentage of circulating hairy cells (r 2 = 0.17; p = 0.017) and the percentage of bone marrow infiltration (r 2 = 0.15; p = 0.009), but not splenomegaly (p = 0.167) or LDH levels (r 2 = 0.02; p = 0.369). We found a significant difference between serum sIL-2R levels measured before and after therapy (median 16.185 vs 599 kU/L respectively; p &amp;lt; 0.001), with a median reduction in sIL-2R levels of 15.628 kU/L after treatment with purine analogues. A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L). Among responding patients, the absolute value of log10(sIL-2R) levels measured 6 months after therapy was a predictor of shorter TTNT in univariate analysis (HR 15.14; 95% CI 1.3 - 176; p = 0.03). Furthermore, sIL-2R correlated with the depth of response. Post-therapy median sIL-2R levels were significantly lower in patients achieving a complete remission (CR) versus those who did not (median 568 kU/L for CR vs. 3.272 kU/L for partial remission/stable disease; p = 0.002). A statistically significant difference was also observed in post-therapy sIL-2R levels between MRD- and MRD+ patients (median 502 vs 724 kU/L; p = 0.003) (Figure 1A). In the patients that underwent yearly serial sIL-2R measurements during follow-up, a rise from the nadir after therapy in serum sIL-2R levels of ≥ 25% between two samples was associated with both shorter TTC (HR 26.2; 95 % CI 3.44 - 200; p &amp;lt; 0.001) (Figure 1B) and TTNT (HR 8.83; 95 % CI 1.9 - 40.9; p &amp;lt; 0.001). Conclusion The consistent reduction in sIL-2R levels after therapy and their correlation with other standard disease parameters show how serum sIL-2R levels could be an effective marker of tumor burden in HCL. While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse.

Performance of serum soluble interleukin-2 receptor as a diagnostic marker for lymphoma in patients with fever

There have been few reports on the diagnostic performance of soluble interleukin-2 receptor (sIL-2R) for lymphoma. A cross-sectional study was conducted at a university hospital; all patients who were admitted to the Division of General Internal Medicine and underwent serum sIL-2R testing were included. Patients were divided into two groups based on the presence of fever (≥ 38.0 °C). Among 602 patients, 421 had fever and 76 were diagnosed with lymphoma (48 of the 76 were in the febrile group). In all patients, the area under the receiver operating characteristic curve (AUROC) of sIL-2R for the diagnosis of lymphoma was 0.81 [95% confidence interval (CI), 0.75–0.87]. The AUROC was significantly higher in the febrile group (0.88; 95% CI, 0.81–0.94) than in the afebrile group (0.75; 95% CI, 0.65–0.85). In the febrile group, the sensitivity and specificity were 81.2% and 82.3%, respectively, with an optimal cutoff value of 3,250 U/mL. In the afebrile group, they were 89.3% and 54.9%, respectively, with a cutoff value of 868 U/mL. Serum sIL-2R showed high performance as an adjunctive diagnostic marker for lymphoma, particularly among febrile patients. Different cutoff values should be used for patients with and without fever to maximize diagnostic performance.

Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults

Objective: To retrospectively analyze literature reports and summarize the clinical characteristics of liver failure in patients accompanied with adult hemophagocytic syndrome (HPS). Methods: The Wanfang, CNKI, VIP, PubMed, and Ovid databases were searched for relevant literature on liver failure patients accompanied with adult HPS published from January 1980 to May 2022. The final included literature was systematically reviewed after screening. Results: There were a total of 77 liver failure cases accompanied with adult HPS, with an average age of (41.8 ± 12.5) years. The most common clinical manifestations of these cases were persistent high fever, fatigue, gastrointestinal symptoms, and severe jaundice. The imaging changes were not specific, and the most common was hepatosplenomegaly. Laboratory examination showed a significant increase in serum total bilirubin, lactate dehydrogenase, triglycerides, and soluble interleukin-2 receptor levels, as well as serum ferritin, while there was a decrease in prothrombin activity, natural killer cell activity, and hemocytopenia of two or more lineages in peripheral blood. Myelogram examination showed hemophagocytosis. Adult HPS secondary to infection was more likely to be accompanied with liver failure (55.8%), with an overall case fatality rate of 84.4%. Conclusion: Patients with liver failure accompanied with adult HPS have an extremely high mortality rate and a poor prognosis. Early diagnosis and treatment are the keys to improving the prognosis.

Prognostic value of post-treatment serum soluble interleukin-2 receptor in newly diagnosed diffuse large B-cell lymphoma patients who achieved complete metabolic response following R-CHOP therapy

Patients with DLBCL achieving complete metabolic response (CMR) after initial treatment with R-CHOP generally have a favourable prognosis; however, there are no established prognostic biomarkers for relapse in these patients. Soluble interleukin-2 receptor (sIL-2R) levels at diagnosis are prognostic factors in patients with DLBCL. However, the significance of post-treatment sIL-2R levels is unclear. To determine the significance of post-treatment serum sIL-2R levels on subsequent relapse and survival, we retrospectively analysed 485 patients with newly diagnosed DLBCL who received R-CHOP treatment and achieved CMR. The cumulative incidence of relapse (CIR) was significantly higher in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (five-year CIR; 38.8% vs. 12.8%). The prognostic value remained significant in multivariable analysis (hazard ratio, 2.30; p < 0.001). Five-year progression-free survival (49.0% vs. 83.5%) and overall survival (61.7% vs. 91.6%) rates were lower in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (p < 0.001 for both). In patients with newly diagnosed DLBCL who achieved CMR after R-CHOP treatment, the post-treatment serum sIL-2R level was an independent prognostic marker of subsequent relapse and survival.

Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance.

Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630-0.884, P = 0.001) and 0.826 (95% CI 0.717-0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Role of Serum Soluble Interleukin-2 Receptor Level in the Diagnosis of Sarcoidosis: A Systematic Review and Meta-Analysis.

Serum Soluble Interleukin-2 Receptor (sIL-2R) levels are used clinically as a disease activity marker for systemic sarcoidosis. Studies have investigated the diagnostic role of serum soluble interleukin-2 receptor (sIL-2R) level for sarcoidosis relative to biopsy. We performed a systematic review and meta-analysis of studies evaluating the diagnostic utility of sIL-2R. We carried out an electronic search in Medline, Embase, Google Scholar, and Cochrane databases using keyword and Medical Subject Heading (MeSH) terms: sarcoidosis and sIL-2R. Studies evaluating the sIL-2R levels as a diagnostic tool in clinically diagnosed or biopsy-proven sarcoidosis patients compared to control groups with non-sarcoidosis patients were included. Forest plots were constructed using a random effect model depicting pooled sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. We selected ten studies comprising 1477 patients, with 592 in the sarcoidosis group and 885 in the non- sarcoidosis group. Pooled sensitivity and specificity of sIL-2R levels were 0.88 (95% CI: 0.75-0.95) and 0.87 (95% CI 0.73-0.94) respectively. Pooled negative predictive value and positive predictive value were 0.91 (95% CI 0.77-0.97) and 0.85 (95% CI 0.59-0.96) respectively with diagnostic accuracy of 0.86 (95% CI 0.71- 0.93). In addition to its utility as a marker of sarcoidosis disease activity, sIL-2R has high diagnostic accuracy. Despite the limitations of the heterogenous sarcoidosis population and different sIL-2R cutoffs, our results suggest that sIL-2R is an important biomarker that can be used to confirm sarcoidosis diagnosis in unconfirmed or unclear cases.

Usefulness of Serum Soluble Interleukin-2 Receptor Levels for Differentiating between PCNSL and SCNSL.

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.

Acquired L1196M ALK mutation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma during alectinib administration.

Acquired L1196M ALK mutation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma during alectinib administration.

Improving Prognosis of Aggressive Natural Killer Cell Leukemia in Japan

Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature NK cell neoplasm that is closely associated with the Epstein-Barr virus (EBV). Patients with ANKL show a fulminant clinical course and poor prognosis with a median overall survival (OS) of a few months after diagnosis. L-asparaginase (L-asp)-containing chemotherapies and allogeneic hematopoietic stem cell transplantation (HSCT) are considered as effective therapeutic strategies. However, owing to the rarity of this disease, the characteristics and outcomes of ANKL remain unclear. Methods Data of 103 patients diagnosed with ANKL between 2002 and 2021 from 64 hospitals were retrospectively analyzed. Diagnosis was based on the World Health Organization classification and was verified by two co-authors (AF and RS). Patients registered in our previous ANKL studies were excluded. Results Patient's median age was 50 years (range, 17-90 years), and males accounted for 58%. Twelve patients (12%) had a medical history of chronic active EBV infection (9%), severe mosquito bite allergy (5%), and chronic lymphoproliferative disorder of NK cells (1%). B symptoms were commonly observed at the time of diagnosis (89%). Performance status (PS) was poor (2-4) in more than half of patients (53%). The median percentage of ANKL cells was 20.0% (range, 0-93.4) in bone marrow (BM) and 10.3% (range, 0-89) in peripheral blood (PB). ANKL cells express CD2 (95%), CD7 (53%), CD16 (41%), CD56 (95%), and EBER (86%). Fifty-two patients analyzed (58%) had chromosomal abnormalities by G-banding method, including chromosome 17 abnormalities in 19, deletion of 6q in 11, and isochromosome 7 in 5. Blood tests at diagnosis typically showed pancytopenia with a median white blood cell count of 2,900/μl, hemoglobin level of 10.3g/dl, and platelets 4.3×104/μl. High serum lactate dehydrogenase and soluble interleukin-2 receptor level were also observed (median, 882U/l and 8,475U/dl, respectively). The most common extra-nodal site of involvement was the BM (100%), followed by the spleen (84%), liver (70%), and PB (59%). Median OS of the present cohort was 5.3 months, and 1-year OS was 25.7%. Prognosis was significantly better in patients who underwent HSCT than in those who did not undergo HSCT (P < 0.001). The median OS and 1-year OS were 12.0 months and 52.3% in the former group and 1.7 months and 3.8% in the latter. Eighty-three patients received multi-agents-containing chemotherapy, while the others received single agent or did not receive any anti-lymphoma chemotherapy owing to poor general condition. The most common first-line chemotherapy was the SMILE regimen (39%), followed by anthracycline-based regimens, mainly CHOP (24%), DeVIC (15%) and other L-asp-containing regimens (8%). The response rate was highest in patients treated with SMILE (66%), followed by those who received other L-asp-containing regimens (57%), DeVIC (36%) and anthracycline-based regimens (32%). OS was significantly better in patients who received SMILE than in those who did not receive SMILE (1-year OS 39.3% vs. 12.1%, P < 0.001, Figure). Furthermore, the HSCT rate was significantly higher in patients who received SMILE (68% vs. 26%, P < 0.001). Multivariate analysis using the Cox proportional hazards model showed good PS (0-1) (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.91, P = 0.03), administration of SMILE (HR 0.43, 95% CI 0.23-0.80, P = 0.009), and HSCT (HR 0.26, 95% CI 0.12-0.58, P = 0.001) were independent factors associated with favorable OS. Conclusion The present study showed better OS as compared with our previous study. The SMILE chemotherapy and HSCT were suggested to be key components of the therapeutic strategy for ANKL. Further studies are warranted to validate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical significance of serum and vitreous soluble interleukin-2 receptor in patients with intraocular lymphoma

BackgroundIntraocular lymphoma (IOL) is a masquerade syndrome that mimics uveitis, making diagnosis difficult. The serum soluble interleukin-2 receptor (sIL-2R), which is cleaved by matrix metalloproteinase (MMP) -2 and MMP-9, has been recognized as a tumor-related biomarker of malignant lymphomas. The aim of this study was to review the reliability of serum and vitreous sIL-2R for distinguishing IOL from uveitis.MethodsPatients who underwent diagnostic vitrectomy for marked vitreous haze at Hokkaido University Hospital between April 2014 and June 2019 were enrolled. The patients were divided into an IOL group and a uveitis group, according to the pathology of their vitreous samples. The IOL group was further divided at the time of vitrectomy into patients who already had extraocular involvement (IOL with extraocular involvement group) and patients with no evidence of having extraocular involvement (IOL without extraocular involvement group). Serum sIL-2R, and intravitreal sIL-2R, MMP-2, and MMP-9 levels were assessed.ResultsTwenty-five eyes of 25 patients, and 15 eyes of 15 patients were included in the IOL group and uveitis group, respectively. The serum sIL-2R levels were significantly lower in the IOL group than in the uveitis group (P < 0.05), and 20.0% and 66.7% in the IOL and the uveitis group showed high sIL-2R value above the normal range. Vitreous sIL-2R tended to be higher in the IOL group than in the uveitis group (P = 0.80). Serum sIL-2R was significantly lower in the IOL without extraocular involvement group than in the IOL with extraocular involvement group (P < 0.05); 5.9% in the IOL without extraocular involvement group and 50.0% in the IOL with extraocular involvement group showed high sIL-2R value above the normal range. Vitreous sIL-2R, MMP-2, and MMP-9 tended to be higher in the IOL with extraocular involvement group than in the IOL without extraocular involvement group (P = 0.30, < 0.05, 0.16).ConclusionsSerum sIL-2R is often within the normal range in IOL patients. Even if it is within the normal range, the possibility of IOL should be considered. Serum sIL-2R is not a reliable biomarker for IOL, whereas vitreous sIL-2R may be useful for the diagnosis of IOL.

Correlation between serum levels of PTX-3, SIL-2R, inflammatory markers, and APACHE II scores in patients with severe acute pancreatitis.

To investigate the correlation of serum pentraxin 3 (PTX-3), soluble interleukin-2 receptor (SIL-2R), C-reactive protein (CRP), procalcitonin (PCT) levels, and acute physiology and chronic health evaluation II (APACHE II) scores in patients with severe acute pancreatitis (SAP). A total of 30 patients with SAP from October 2020 to October 2021 were selected as the SAP group, and 42 patients with mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis (MSAP) was selected as the control group. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores were evaluated. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores at admission in the SAP group were significantly higher than those in the control group (all P < .05). Spearman analysis showed that serum PTX-3, SIL-2R, CRP, and PCT levels were positively correlated with APACHE II scores (all P < .05). The mortality rate within 28 days was 26.7% in the SAP group; moreover, the serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores at admission in the death group were significantly higher than those in the survival group (all P < .05). The receiver operating curve showed that the combined prediction value of all indicators (PTX-3 + SIL-2R + CRP + PCT + APACHE II) was superior to the single indicators, and the diagnostic sensitivity and specificity were 90.9% and 84.2%, respectively. Serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores have high guiding significance in early diagnosis and prognostic evaluation of SAP patients.

Serum Soluble Interleukin 2 Receptor Alpha vs. Urinary Parameter and Serum Immunological Markers as a Monitoring Tool of Treatment Response of Lupus Nephritis and their Relation to Lupus Nephritis Class on Renal Biopsy

Background: Lupus Nephritis (LN) is one of the most common and serious manifestations in SLE patients that causes significant morbidity and mortality. Current conventional biomarkers for LN are sometimes unable to predict treatment response of lupus nephritis. Recently serum soluble interleukin-2 receptor alpha (sIL-2 R alpha) is shown to be a good marker to predict treatment response of LN. Objective: To compare serum sIL-2R alpha with other commonly used markers as a marker of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with lupus nephritis after kidney biopsy were included in this study. Serum soluble interleukin-2 receptor alpha, 24 hrs UTP, anti-dsDNA, complements level (C3 &amp; C4) were measured in all patient at baseline, 3-months and 6- months after treatment. Serum soluble interleukin-2 receptor alpha level was measured by ELISA and is expressed as pg/mg. Serum sIL-2R alpha as well as conventional biomarker value were compared before and after treatment and in between treatment response and non-response group. Results: Serum sIL-2R alpha levels were significantly higher in patients of proliferative lupus nephritis (Class III &amp; Class IV) than non-proliferative lupus nephritis (Class V) at baseline (3934.3 ± 1095.2, 3934.3 ± 1095.2 &amp; 1801.98 ± 205.8 pg/L respectively) and levels were decreased significantly 6 months after treatment (p &lt;0.001). Serum sIL-2R alpha levels were also significantly higher in non-remission proliferative group then remission proliferative group (4071.60 ± 769.91 vs 5169.20 ± 394.76) with p value 0.008 at baseline. In contrast no significant difference were observed for 24 hrs UTP levels at baseline between this group which suggest that serum sIL-2R alpha are more sensitive marker than 24 hrs UTP in predicting treatment response of lupus nephritis. Conclusions: Serum sIL-2R alpha might be a valuable serological biomarker to diagnose and to predict and monitor the treatment response of lupus nephritis.

Serum soluble interleukin-2 receptor (sIL-2R) is an accurate biomarker for dengue-associated hemophagocytic lymphohistiocytosis syndrome diagnosed by Hscore

ObjectiveHemophagocytic lymphohistiocytosis is a potentially fatal complication of severe dengue fever. Here we evaluated the serum soluble IL-2R levels as potential biomarker for identifying HLH in patients with dengue fever.MethodsIn this cross-sectional study conducted in a tertiary care center of a teaching hospital, subjects with dengue and fever of more than 5 days, leukopenia/thrombocytopenia and/or hepatosplenomegaly were studied. Data were collected to compare sIL-2R values and serum ferritin with Hscore and Histiocyte Society 2004 criteria. Relevant statistical methods were used.Results80 subjects with severe dengue fever were analyzed with relevant investigations. Mean H score was 219.2 ± 17.6 in 18 dengue patients with HLH v/s 166.2 ± 11.2 in 62 patients without HLH (p = < 0.001). Serum ferritin (11,230.5 v/s 7853.5, p = 0.013) and sIL-2R (32,917.5 v/s 6210, p = < 0.001) were significantly higher in those patients with HLH. sIL-2R correlated very well with HScore (r = 0.98, p < 0.001) compared to ferritin (r = 0.51, p < 0.001) with an AUROC of 1.00 compared to 0.694 (95% CI 0.557–0.831) of serum ferritin for diagnosing HLH. A cut-off value of 10,345 pg/ml for sIL-2R had a sensitivity and specificity of 100% for HLH, whereas, a ferritin value of 8613 ng/ml had only 67% sensitivity and 55% specificity.ConclusionsIL-2R could be a single most useful biomarker to differentiate dengue fever patients who are likely to progress to HLH, from those that are not. Full workup for HLH could be limited only to those patients with elevated sIL-2R, especially in resource limited settings.

Intravenous tocilizumab for the treatment of giant cell arteritis: a phase Ib dose-ranging pharmacokinetic bridging study

BackgroundSubcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA).MethodsPatients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration (Cmax), minimum concentration (Ctrough), area under the curve over a dosing interval (AUCτ), and mean concentration (Cmean) of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy.ResultsIn 24 patients, the median (range) age was 65.5 (57–90) years, and 62.5% were female. TCZ exposures (Cmax and AUCτ) were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study.ConclusionsBoth doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The Cmax and Cmean achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and Ctrough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks.Trial registrationClinicalTrials.gov, NCT03923738

Effects of Different Anesthetic and Analgesic Methods on Cellular Immune Function and Stress Hormone Levels in Patients Undergoing Esophageal Cancer Surgery.

The change of perioperative immune function in patients with esophageal cancer is mainly caused by the joint action of surgical trauma and anesthesia. In our study, we aimed to investigate the effects of different anesthetic methods on the changes of T lymphocyte subsets and cytokines in peripheral blood of patients with esophageal cancer surgery. 50 patients with esophageal cancer were divided into the study group and the control group. Among them, the patients in the control group chose intravenous anesthesia and received self-controlled intravenous analgesia after surgery. Patients in the study group chose thoracic epidural anesthesia combined with general anesthesia, undergoing self-controlled epidural analgesia after surgery; serum interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) were measured by ELISA. Serum stress hormones GH and sIL-8 were measured by radioimmunoassay. Both groups of patients achieved significant postoperative analgesia, but the VAS score in the study group at the T2–T4 time point was lower than that in the control group. The serum GH concentration in the study group increased at T1 and reached its highest peak at T2, then decreased. The serum IL-8 concentration of the two groups showed a downward trend from T1 to T4. Thoracic epidural anesthesia combined with general anesthesia for postoperative epidural analgesia can relieve the degree of cellular immunosuppression during and after surgery. Moreover, the thoracic epidural block combined with general anesthesia for esophageal cancer surgery and epidural analgesia after surgery for patients are anesthetic and analgesic methods with clinically significant effects. Our research results have a positive effect on the promotion of postoperative rehabilitation in patients with malignant cell tumors.