Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months.ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525 ng/mL) in 14 (15.2%) patients and low (ATP < 225 ng/mL) in 78 (84.8%); no patients had a strong response (ATP ≥ 525 ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p = 0.043). Similar acute rejection rates were recorded in patients with mean ATP ≥ 225 vs. <225 ng/mL during the study period (7.1% vs. 9.1%, p = 0.81).ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.     

Deciphering the role of transforming growth factor-beta 1 as a diagnostic-prognostic-therapeutic candidate against hepatocellular carcinoma

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-β family, TGF-β1 modulates most of its biological outcomes. Despite the abundant expression of TGF-β1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-β1 levels, contributing to poor prognosis and survival. Additionally, elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms. TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC. Moreover, TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors. This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis, prognosis, and therapy against HCC.     

Chronic rejection after liver transplantation: Opening the Pandora’s box

Chronic rejection (CR) of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation. Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy, CR still represents an important cause of graft injury, which might be irreversible, leading to graft loss requiring re-transplantation. To date, we still do not fully appreciate the mechanisms underlying this process. In addition to T cell-mediated CR, which was initially the only recognized type of CR, recently a new form of liver allograft CR, antibody-mediated CR, has been identified. This has indeed opened an era of thriving research and renewed interest in the field. Liver biopsy is needed for a definitive diagnosis of CR, but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation. Moreover, the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury, which should not be disregarded. Therapies for CR may only be effective in the “early” phases, and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage. Herein, we provide an overview of the current knowledge and research on CR, focusing on early detection, identification of non-invasive biomarkers, immunosuppressive management, re-transplantation and future perspectives of CR.     

Prevention and treatment of COVID-19 in patients with benign and malignant blood disorders

Patients with moderate to severe immunosuppression, a condition that is common in many hematologic diseases because of the pathology itself or its treatment, are at high risk for COVID-19 and its complications. While empirical data are sometimes conflicting, this heightened risk has been confirmed in multiple well-done studies for patients with hematologic malignancies, particularly those with B-cell lymphoid malignancies who received lymphocytotoxic therapies, those with a history of recent hematopoietic stem cell transplant and chimeric antigen receptor T-cell therapy, and, to a lesser degree, those with hemoglobinopathies. Patients with immunosuppression need to have a lower threshold for avoiding indoor public spaces where they are unable to effectively keep a safe distance from others, and wear a high-quality well-fitting mask, especially when community levels are not low. They should receive an enhanced initial vaccine regimen and additional boosting. Therapeutic options are available and immunosuppressed patients are prioritized per the NIH.     

儿童肾移植术后激素撤除对生长曲线的影响CSCD

目的探究儿童肾移植术后生长趋势以及激素撤除对于生长曲线的影响。方法回顾性分析2013年5月至2021年3月于郑州大学第一附属医院肾移植科接受肾移植手术的儿童受者临床资料,术后采用他克莫司+霉酚酸+糖皮质激素(glucocorticoid,GC)三联免疫治疗方案,根据术后3个月内是否撤除激素分为撤激素组和未撤激素组,观察两组各时间段内生长发育变化情况,比较两组在撤除激素前后各时间段生长变化速率的差异。结果共214例患儿纳入研究,其中未撤激素组142例,撤激素组72例;两组术前身高年龄别评分(height for age Z-score,HAZ评分)分别为(-1.60±1.48)分和(-1.44±1.38)分,差异无统计学意义(P=0.539);术后1年时两组HAZ评分分别为(-0.95±1.31)分和(-0.51±1.10)分,差异具有统计学意义(P=0.046)。两组术前、术后3个月、术后6个月的HAZ评分差异均无统计学意义(P>0.05)。两组手术后前3个月、手术后3~6个月HAZ评分的变化速率差异均无统计学意义(P>0.05),而手术后6~12个月的差异具有统计学意义(P=0.016)。结论慢性终末期肾病(end-stage renal disease,ESRD)患儿术前存在不同程度的发育迟缓,接受肾移植后患儿生长缺陷有所弥补,术后不同时间段身高发育速率有所不同,在术后追赶性生长的高峰期到来之前撤除激素对于儿童手术后远期发育有积极的影响。     

A Toxicokinetic Study of Nickel‐Induced Immunosuppression in Rats

Abstract

The aim of the present study was to investigate dose‐ and time‐dependent effects of NiCl₂ on T‐lymphocyte and macrophage‐derived cytokine production in rats. Moreover we have determined the concentrations of nickel in the plasma that are required to elicit alterations in T‐lymphocyte and macrophage function. NiCl₂ suppressed T‐lymphocyte proliferation and Th1 (IFN‐γ) and Th2 (IL‐10) cytokine production in a dose‐ and time‐dependent fashion. In addition, NiCl₂ inhibited production of the pro‐inflammatory cytokine TNF‐α and increased production of the anti‐inflammatory cytokine IL‐10 from lipopolysaccharide (LPS) stimulated cultures. We have determined that the minimal plasma concentrations of nickel required to provoke immunosuppression are in the range 209–585 ng/mL. In the time‐course study NiCl₂ (3.3 mg/kg) provoked immunological changes that were maximal 1 h following administration, and some of these changes persisted for up to 24 h post administration. Overall these data clearly demonstrate that NiCl₂ suppresses T‐cell function and promotes an immunosuppressive macrophage phenotype in rats. This study also indicates that measuring T‐cell proliferation is as sensitive a marker of NiCl₂‐induced immunotoxicity as measuring T‐cell or macrophage cytokine production. Co‐measurement of circulating nickel concentrations and immune parameters yields valuable information with regard to the potency of nickel to alter immune function in vivo. These data also suggest that quite a large quantity of nickel needs to reach the systemic circulation before any adverse effects on immune function are observed.     

六月青皂苷对免疫抑制小鼠免疫功能的影响

目的:研究六月青皂苷(Liuyueqing Saponins,LYQS)对免疫抑制小鼠免疫功能的影响.方法:实验动物随机分为5组:空白对照组、环磷酰胺(Cyclophosphamide,CTX)模型组和LYQS高、中、低剂量组.除空白对照组外,其它各组小鼠于给药的第2、4、6、8、10天腹腔注射CTX(0.02 g·kg-1·d-1)造模.空白对照组和CTX模型组均用生理盐水(20ml·kg-1·d-1)灌胃;LYQS高、中、低剂量+CTX组用LYQS[(1、0.5、0.25)g·kg-1·d-1)]灌胃,给药10天后,检测小鼠血中红细胞(RBC)、白细胞(WBC)、血小板(PLT)数量、血红蛋白(Hb)含量和TNF-α、IFN-γ、TGF-β1、IL-2含量;检测胸腺指数、脾脏指数、脾淋巴细胞转化功能、腹腔巨噬细胞吞噬功能、NK细胞杀伤活性和血清50％溶血值(HC50);观察二硝基氟苯诱导的迟发型超敏反应.结果:与CTX模型组比较,LYQS各剂量组的胸腺指数明显提高;高剂量组的WBC数量、耳肿胀度明显提高;高、中剂量组的RBC、Hb、IL-2、脾脏指数、HC50、脾淋巴细胞转化功能、巨噬细胞廓清指数和吞噬指数明显提高;高、中剂量组的TGF-β1明显降低.结论:LYQS能增强CTX免疫抑制模型小鼠的特异性及非特异性免疫反应,提高其免疫功能.     

SARS-CoV-2-induced immunodysregulation and the need for higher clinical suspicion for co-infection and secondary infection in COVID-19 patients

Cases of co-infection and secondary infection emerging during the current Coronavirus Disease-19 (COVID-19) pandemic are a major public health concern. Such cases may result from immunodysregulation induced by the SARS-CoV-2 virus. Pandemic preparedness must include identification of disease natural history and common secondary infections to implement clinical solutions.     

Infection mechanism of biofilm‐forming Staphylococcus aureus on indwelling foreign materials in mice

Indwelling foreign‐body infections are a critical medical problem, especially in immunocompromised patients. To examine the pathogenicity of biofilm‐forming bacteria settling on foreign materials, mice implanted with plastic discs were infected with Staphylococcus aureus. After opening a wide subcutaneous pocket on the dorsal side of mice with or without temporal leukocytopenia, a plastic sheet was placed in the left subcutaneous space; subsequently, bacteria in a planktonic state were dispersed over the subcutaneous space. Bacterial numbers were examined 7 days after inoculation. In subcutaneous tissue on the right, S. aureus was found only in leukocytopenic mice. Meanwhile, bacteria were detected on the plastic and neighbouring tissue in both leukocytopenic and normal mice; however, colony‐forming analysis indicated that leukocytopenic mice possessed significantly more bacteria. Tissue reaction against bacteria was pathologically examined. Invading S. aureus induced severe inflammation. In transient leukocytopenic mice, bacterial microcolonies formed on the plastic as well as in the developed necrotic tissue – both of which were shielded from inflammatory cell infiltration – result in bacteraemia. These results indicate that biofilm‐forming S. aureus settling on indwelling foreign material are tolerant against host immunity and assault neighbouring tissue, which may lead to chronic wound infection.