Secondary Immunodeficiency and Hypogammaglobulinemia with IgG Levels of <5 g/L in Patients with Multiple Myeloma: A Retrospective Study Between 2012 and 2020 at a University Hospital in China.

BACKGROUND Infections are the main cause of mortality and morbidity in multiple myeloma (MM) patients. However, adult immunodeficiency specialists in China are lacking, and the care of secondary immunodeficiency (SID) and the prognostic role of hypogammaglobulinemia in MM is unknown. MATERIAL AND METHODS MM patients (295) were retrospectively analyzed between January 2012 and 2020 in Zhejiang Provincial People's Hospital, Hangzhou Medical College. MM patients with immunoglobulin (Ig) G <5 g/L were defined as SID patients. The care of these patients and the prognostic role of IgG <5 g/L were analyzed RESULTS Forty-five of 295 MM patients with IgG <5 g/L were defined as SID patients. These 45 patients mainly had recurrent infections, especially pulmonary bacterial infections; 2 patients had them 5 times/year. The median survival time was significantly shorter in MM patients with SID (24 vs 66 months). More importantly, the multivariate and univariate analysis revealed that IgG <5 g/L was an independent prognostic factor for MM patients. CONCLUSIONS Ig replacement therapy or prophylactic antibiotics for MM patients with SID were lacking in this single retrospective study. IgG <5 g/L could be a prognostic marker for MM patients.

Number of Stent Retriever Passes Associated with Clinical Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

OBJECTIVE: To evaluate the association between the number of stent retriever (SR) passes and clinical outcome after mechanical thrombectomy (MT) in patients with acute ischemic stroke(AIS). METHODS: We retrospectively analyze data collected from consecutive patients with large vessel occlusion (LVO) in anterior circulation treated with MT. Baseline characteristics, number of SR passes, symptomatic intracranial hemorrhage (sICH), clinical outcome measured by modified Rankin Scale (mRS) at 90 days after MT were collected. Multivariate logistic regression analysis was performed to assess the association between number of SR passes and patients' clinical outcome. RESULTS: 134 patients with LVO achieved successful reperfusion (mTICI 2B/3) were enrolled. Univariate analysis showed that patients with favorable outcomes were less likely to need more than three passes of SR (9.8%vs39.7%, p = 0.001). In a multivariable analysis, baseline NIHSS score (OR 0.922, 95%CI 0.859∼0.990, p = 0.025), more than three passes of SR (OR 0.284, 95%CI0.091∼0.882, p = 0.030) and symptomatic intracranial hemorrhage (OR 0.116,95%CI0.021∼0.650, p = 0.014) each independently predicted poor outcome after MT at 90 days. CONCLUSION: The need for more than three passes of SR may be used as an independent predictor of poor outcome after MT in patients with acute ischemic stroke at 90 days.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen-DR- cell differentiation in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 (PD-1) and its ligand, PD-L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD-1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease-free survival after tumor resection in NSCLC. We found significantly higher number of Tfh cells but lower serum interleukin (IL)-21 levels in NSCLC patients, especially in those with advanced stage (III and IV), indicating that the function of Tfh cells to produce IL-21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the PD-1+ -Tfh2 and PD-1+ -Tfh17 subtypes. Functional analysis showed that Tfh cells from NSCLC patients induced the differentiation of regulatory B cells and CD14+ human leukocyte antigen (HLA)-DR- cells. Interestingly, the number of Tfh1 subtypes in NSCLC patients was negatively correlated with disease-free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in NSCLC. Rescuing Tfh functions therefore represents a potential therapeutic strategy in NSCLC.

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis.

Objective: Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML. Methods: Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish in vitro models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot. Results: The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells. Conclusion: PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis.

Defects and countermeasures in laboratory diagnosis of rare IgE multiple myeloma.

BACKGROUND: IgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM. METHODS: The serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed. RESULTS: Upon admission to our hospital, the patient's serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed "M-like protein aggregation bands" in all lanes. After pretreatment with 1% ß-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the "M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 107 IU/mL, whereas 7 other testing institutions reported IgE levels ranging from 1.0 to 1100 IU/mL. CONCLUSION: High-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

A clinician survey for management of the secondary immunodeficiency caused by hematological malignancies in China.

ABSTRACT: Unlike Western countries, there are still few clinical immunology specialists in China, and the optimal care for secondary immunodeficiency caused by hematological malignancies is unknown. Therefore, we initiated this clinician survey study to describe the current situation of the care for malignancy patients with hypogammaglobulinemia in China.We adapted a previously published online questionnaire of current clinical practices regarding the management of secondary immunodeficiency caused by hematological malignancies and then distributed the questionnaire to 52 hematologists in China via WeChat mobile software; the survey collected demographic details, starting dosage, target immunoglobulin (Ig) level, monitoring, criteria for stopping Ig replacement, vaccination use, and oral antibiotic prophylaxis for hypogammaglobulinemia patients.Forty-eight hematologists responded. 28(58.33%) respondents had more than 10 years of experience. Nevertheless, 40(83.33%) respondents reported that they did not use any specific criteria for prophylactic Ig replacement in hypogammaglobulinemia patients. However, 27(56.25%) respondents reported that they had used intravenous immunoglobulin (IVIG); however, the starting dose, frequency, and target Ig level were significantly varied. Additionally, the criteria for stopping Ig replacement were significantly varied. Only one respondent (2.08%) used subcutaneous immunoglobulin (SCIG). Moreover, 35(72.92%) respondents reported no vaccination prior to Ig replacement, and 47(97.92%) respondents reported that they had not used antibiotic prophylaxis in secondary hypogammaglobulinemia patients.Official guideline for the care for secondary immunodeficiency (SID) of the hematological malignancies patients should be issued in China, and significant attention of the hematologists should be paid to the use of prophylactic antibiotics and Ig replacement for the care of patients with hypogammaglobulinemia caused by hematological malignancies, as these agents could significantly reduce the infection rate in China.

Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment.

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment. Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3-6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses. Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59-7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017-1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056-2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment. Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.

Elevated levels of follicular T helper cells and their association with therapeutic effects in patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression. Our findings revealed the expansion of circulating CD4+CXCR5+, CD4+ICOS+, CD4+PD-1+ and CD4+CXCR5+ICOS+PD-1+ (Tfh) cells but lower serum IL-21 levels and CD4+ T cell polarization not only to Tfh2 subtypes but also to Tfh17 subtypes in patients with CLL at pretreatment compared to patients with monoclonal B cell lymphocytosis (MBL) and healthy individuals, especially in those with advanced stage, which indicate these Tfh cells could be employed as a novel indicator for disease progression. Moreover, we observed significant correlations of Tfh17 and immunoglobulin heavy chain variable region (IGHV) mutation. Importantly, significantly decreased CD4+ICOS+, CD4+PD-1+ and Tfh cells were found after effective treatments, whereas a significantly high CD4+ICOS+, CD4+PD-1+ and Tfh cells were still found in those with progressive disease after treatments, suggesting that circulating CD4+ICOS+, CD4+PD-1+, Tfh cells could predict therapeutic effects.

Recurrent fever and arthralgia as the presentation of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Chinese girl: a case report and review of the literature.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is characterized by recurrent episodes of inflammation with fever, abdominal pain, chest pain, rash, myalgia, arthralgia, conjunctivitis, and periorbital edema. This condition is a rare autosomal dominant disease that is strongly associated with heterozygous mutations in the tumor necrosis factor (TNF) receptor super family 1A (TNFRSF1A) gene. This condition is believed to be more common in Western countries than in Asian countries, and the AA amyloidosis rate for European countries is estimated to be 10%. Herein, we report the case of a 14-year-old girl with recurrent fever and arthralgia with inflammatory marker elevation for 10 years. After extensive investigation of the infectious etiology with negative results and similar phenomenon observed within her family, the diagnosis of TRAPS was made based on next-generation sequencing, which revealed a T50M mutation; she was also sensitive to corticosteroids. Although none of our TRAPS patients developed AA amyloidosis, we suggest the continual monitoring of urinalysis results and serum amyloid A concentrations during long-term follow-up. Moreover, we also reviewed the related literature and found no Asian patients who had developed AA amyloidosis.

Clinicopathological study of 9 cases of megakaryocytes in pleural and peritoneal fluids.

To systemically analyze megakaryocytes in pleural and peritoneal fluids and their clinical significance. We retrospectively examined 10,846 pleural, peritoneal, and pericardial fluid samples obtained from 3 hospitals over a 20-year period. Megakaryocytes were observed in the pleural fluid samples from 7 patients and peritoneal fluid samples from 2 patients, and the incidence was 0.83%. The clinical diagnoses of these 9 patients included myeloproliferative disorders, trauma, and tumors. The serous effusions in all 9 patients were bloody, and the megakaryocytes could be associated with trauma, bone marrow pollution, extramedullary hematopoiesis, or cancer. Additionally, differentiating between megakaryocytes and tumor cells or nuclear mesothelial cells in the pleural fluid is difficult. Therefore, megakaryocytes should be carefully observed and differentiated in pleural and peritoneal fluids because they can be confused with other cells in the clinic. Altogether, the megakaryocytes in the pleural and peritoneal fluids were mainly associated with contamination in the bone marrow or extramedullary hematopoiesis.

D-Dimer levels are correlated with disease activity in Crohn's patients.

Various indices have been used to assess Crohn's disease (CD). However, the question of whether the Crohn's Disease Activity Index (CDAI) is associated with coagulation function has not been fully confirmed. In this study, we examined the association between CDAI and the coagulation and fibrinolysis parameters. In a retrospective and observational cohort study, the CDAI of 108 patients from two hospital centers was calculated, and its correlations with the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalization ratio (INR), fibrinogen (Fg) and plasma D-Dimer were investigated. Significant differences were found for PT, APTT, TT, INR, Fg and D-Dimer between the healthy controls and CD patients. However, no significant difference was found between the CDAI-High and CDAI-Low groups of CD patients. Moreover, the CDAI was positively correlated with the level of D-Dimer in CD patients of two hospitals, regardless of the detection method (hospital 1: r=0.3268, p= 0.0042; hospital 2: r=0.5553, p=0.0008). Among the blood coagulation and fibrinolysis parameters, the D-Dimer level was highly correlated with CDAI in CD patients. Thus, the level of D-Dimer expression may be a promising new marker for assessing CD disease activity.

RETRACTED: Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The Editor-in-Chief has retracted this article due to serious problems with copied and re-labeled images in several figures. Specifically, the problematic items are the HC and Stage I samples in figure 1D (IL-10/CD19) and figure 2B (CD127/CD25), in which the flow dot plots outside of the boxes are identical. This strongly suggests that the data was manipulated. The authors were unable to provide the raw data files to prove otherwise. This makes the overall conclusions of the paper unreliable and violates our ethical publishing policies. The corresponding author, Liannv Qiu takes full responsibility and apologizes to all co-authors in this article, and the editors and readership of Human Immunology for any negative impact this may have on the journal.