OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance.
METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data.
RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model.
CONCLUSIONS: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

An asymptomatic 75-year-old man who underwent transverse colon cancer surgery two years previously presented with retroperitoneal fibrosis (RPF) around the ventral sacral and right external iliac artery and vein on abdominal computed tomography (CT) during a routine surveillance visit. We assumed cancer recurrence or immunoglobulin G4 (IgG4)-related disease (RD), but although generic tumor markers and IgG4 levels were normal, soluble interleukin 2 receptor (sIL-2R) was elevated at 569 U/mL (reference: 122-496 U/mL). No diagnosis was made at this time, and the patient was followed up. He subsequently developed edema of both lower extremities. Abdominal enhanced CT showed an enlarged RPF without invasion of surrounding organs and with a delayed contrast effect, and positron emission tomography-CT showed fluorodeoxyglucose accumulation in the same area but a lower standardized uptake value (SUV) than at the time of transverse colon cancer diagnosis. Although generic tumor markers and IgG4 levels remained within the reference range, sIL-2R was further elevated to 1100 U/mL. An open biopsy and histopathology showed a high IgG4/IgG-positive cell ratio and infiltration of IgG4-positive plasma cells. The patient was finally diagnosed with IgG4-RD RPF. In cases of RPF after colorectal cancer surgery, the combined findings of elevated sIL-2R, lack of infiltration into surrounding organs, and lower SUV values ​​than at the cancer site could provide useful information to aid the diagnosis of IgG4-RD RPF.

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation. It usually occurs in children, mainly during the first year of life. Primary hemophagocytic lymphohistiocytosis is more common and usually occurs in immunocompromised patients. Secondary hemophagocytic lymphohistiocytosis, on the other hand, is less common, especially in immunocompetent patients. Here, we intend to present a case of a 55-year-old male patient who had no known immune deficiency, presented with epistaxis, and was found to have Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis.

Aberrant neuronal excitability in the anterior cingulate cortex (ACC) is implicated in cognitive and affective pain processing. Such excitability may be amplified by activated circulating immune cells, including T lymphocytes, that interact with the central nervous system. Here, we conducted a study of individuals with chronic pain using magnetic resonance spectroscopy (MRS) to investigate the clinical evidence for the interaction between peripheral immune activation and prefrontal excitatory-inhibitory imbalance. In thirty individuals with chronic musculoskeletal pain, we assessed markers of peripheral immune activation, including soluble interleukin-2 receptor alpha chain (sCD25) levels, as well as brain metabolites, including Glx (glutamate + glutamine) to GABA+ (γ-aminobutyric acid + macromolecules/homocarnosine) ratio in the ACC. We found that the circulating level of sCD25 was associated with prefrontal Glx/GABA+. Greater prefrontal Glx/GABA+ was associated with higher pain catastrophizing, evaluative pain ratings, and anxiodepressive symptoms. Further, the interaction effect of sCD25 and prefrontal Glx/GABA+ on pain catastrophizing was significant, indicating the joint association of these two markers with pain catastrophizing. Our results provide the first evidence suggesting that peripheral T cellular activation, as reflected by elevated circulating sCD25 levels, may be linked to prefrontal excitatory-inhibitory imbalance in individuals with chronic pain. The interaction between these two systems may play a role as a potential mechanism underlying pain catastrophizing. Further prospective and treatment studies are needed to elucidate the specific role of the immune and brain interaction in pain catastrophizing.

We report an autopsy case of advanced esophageal cancer with multiple metastases that presented with a markedly high level of sIL-2R. An 83-year-old man was admitted to our hospital with a 1-week history of epigastric distress, appetite loss, and fatigue. Imaging examinations revealed a large liver tumor. Although the tumor markers for gastrointestinal and liver cancers were within normal limits, the sIL-2R level was extremely high (10,384 U/mL). The patient died immediately after admission due to the rapid course of the disease. An autopsy showed advanced esophageal cancer with multiple metastases, including the liver, lungs, and multiple lymph nodes. In histological examinations, esophageal cancer was a mixture of well- and poorly differentiated squamous cell carcinoma, in which poorly differentiated cancer cells expressed sIL-2R on immunohistochemical staining. However, we failed to detect positive staining for sIL-2R in the lymphocytes. Our findings revealed that solid tumors could express sIL-2R. Although sIL-2R is a tumor marker used for hematological malignancies, such as malignant lymphoma, this case report highlights the value of the measurement of sIL-2R levels in advanced solid tumors, including esophageal cancer. We concluded that sIL-2R has potential as a biomarker in advanced solid tumors for cancer staging and treatment response.

OBJECTIVE: 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%.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

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.

Asian variant intravascular lymphoma (AIVL) is a rare type of intravascular lymphoma that occurs in Asian populations. Syndrome of inappropriate antidiuretic hormone selection (SIADH) frequently occurs in patients with AIVL. Because it remains difficult to diagnose and has a poor prognosis, markers for early diagnosis are required. Although lactase dehydrogenase (LD) and soluble interleukin-2 receptor (sIL-2R) are diagnostic candidates, these markers do not appear to have been used often in prior studies. We present the case of an 87-year-old Japanese man with AIVL complicated by unexplained SIADH with a complaint of anorexia. Computer tomography showed splenomegaly but no lymphadenopathy. Elevated LD and sIL-2R were detected in the blood. The patient was diagnosed with AIVL through a random skin biopsy and was successfully treated with chemotherapy. When a patient presents with SIADH, we should actively look at or measure blood LD and sIL-2R for early diagnosis of ALVL. Further cases are warranted to determine these observations.

Although cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are considered latent viruses, their reactivation occurs in immunosuppressed conditions. We previously reported that CMV and EBV are reactivated in patients receiving immunosuppressive therapy and/or chemotherapy. This retrospective, single-center study aimed to determine the frequency of viral reactivation and clinical characteristics of patients with B cell lymphoma (B-ML) receiving chemotherapy. Twenty-four patients (mean age 73 years, range 40-87 years; male-to-female ratio, 15:9) with diffuse large B cell lymphoma (n = 15), follicular lymphoma (n = 8), or mantle cell lymphoma (n = 1) were enrolled. Serum CMV and EBV DNA levels were analyzed using quantitative real-time polymerase chain reaction in patients with B-ML receiving chemotherapy. We determined the cumulative reactivation of each virus and analyzed the relationship between viral reactivation and clinical characteristics. Three patients experienced relapse or refractory (R/R) disease and the others had de novo lymphomas. The frequencies of CMV and EBV reactivations were 54.2% and 37.5%, respectively. CMV reactivation occurred significantly earlier during chemotherapy courses in R/R patients than in de novo patients (p = 0.0038), while EBV reactivation was frequently found before treatment. Baseline serum levels of soluble interleukin-2 receptor were higher (4318.0 vs. 981.1 U/mL, p = 0.010) and hemoglobin levels were lower (11.1 vs. 13.0 g/dL, p = 0.0038) in patients with EBV reactivation than in those without reactivation. These findings were not observed in patients with CMV reactivation. CMV reactivation was associated with iatrogenic immunosuppression, whereas EBV reactivation was related to immunosuppression by lymphoma, indicating that the mechanisms of these viral reactivations differed.

Acute kidney injury (AKI) is the most common and critical complication in patients with acute myocardial infarction (AMI). This study aims to evaluate the significance of elevated soluble interleukin 2 receptor (sIL-2R) levels in predicting AKI and mortality.
A total of 446 patients with AMI were enrolled between January 2020 and July 2022, including 58 patients with AKI and 388 without AKI. The sIL-2R levels were measured using a commercially available chemiluminescence enzyme immunoassay. Logistic regression analysis was used to examine the risk factors for AKI. Discrimination was assessed based on the area under the receiver operating characteristic curve. The model was internally validated using 10-fold cross-validation.
During hospitalization, 13% of patients developed AKI following AMI, with higher sIL-2R levels (0.61 ± 0.27 U/L vs. 0.42 ± 0.19 U/L, p = 0.003) and in-hospital all-cause mortality (12.1% vs. 2.6%, P < 0.001). The sIL-2R levels emerged as an independent risk factor for both AKI (OR = 5.08, 95% CI (1.04-24.84, p < 0.045) and in-hospital all-cause mortality (OR = 73.57,95% CI 10.24-528.41, p < 0.001) in AMI patients. The sIL-2R levels were found to be useful biomarkers in prediction of AKI and in-hospital all-cause mortality in patients with AMI (AUC: 0.771 and 0.894, respectively). The respective cutoff values for sIL-2R levels in predicting AKI and in-hospital all-cause mortality were determined to be 0.423 U/L and 0.615 U/L.
The level of sIL-2R was an independent risk factor and predictor for both AKI and in-hospital all-cause mortality in patients with AMI. These findings highlight the potential of sIL-2R as a valuable tool for identifying high-risk patients regarding AKI and in-hospital mortality.