Introduction: Chimeric antigen receptor (CAR)-NK cells are considered safer than CAR-T cells due to their short lifetime and production of lower toxicity cytokines. By virtue of unlimited proliferative ability in vitro, NK-92 cells could be utilized as the source for CAR-engineered NK cells. CD22 is highly expressed in B cell lymphoma. The goal of our study was to determine whether CD22 could become an alternative target for CAR-NK-92 therapy against B cell lymphoma.
Material and methods: We first generated m971-BBZ NK-92 that expressed a CAR for binding CD22 in vitro. The expression of CAR was assessed by flow cytometric analysis as well as immunoblotting. The cytotoxicity of the m971-BBZ NK-92 cells towards target lymphoma cells was determined by the luciferase-based cytolysis assay. The production of cytokines in CAR NK-92 cells in response to target cells was evaluated by ELISA assay. Lastly, the cytolytic effect was evaluated by the cytolysis assay mentioned above following irradiation. The level of inhibitory receptor of CAR-expressing cells was assessed by flow cytometry.
Results: CD22-specific CAR was expressed on m971-BBZ NK-92 cells successfully. m971-BBZ NK-92 cells efficiently lysed CD22-expressing lymphoma cells and produced large amounts of cytokines after coculture with target cells. Meanwhile, irradiation did not apparently influence the cytotoxicity of m971-BBZ NK-92 cells. Inhibitory receptor detection exhibited a lower level of PD-1 in m971-BBZ NK-92 cells than FMC-63 BBZ T cells after repeated antigen stimulation.
Conclusions: Our data show that adoptive transfer of m971-BBZ NK-92 could serve as a promising strategy for immunotherapy of B cell lymphoma.
The coronavirus disease 2019 pandemic is an ongoing concern for medical care worldwide. Since its emergence, multiple COVID-19 vaccines have been designed, allowing for more effective control of the pandemic. COVID-19 vaccines, like any other form of medical intervention, may cause adverse and unforeseen side effects, varying in frequency and severity. Determining a correlation between the occurring symptoms and the vaccination is often a challenging task, requiring multiple data sources and reported cases. So far, there have been multiple reports of trigeminal neuralgia developing after COVID-19 vaccination. A 36-year-old woman was admitted to the Emergency Ward due to chronic pain attacks in the left side of her face. The pain appeared two months ago, on the day following the vaccination using the third dose of the Pfizer BioNTech COVID-19 vaccine. At the Neurology Department she was diagnosed with trigeminal neuralgia. Based on the lack of any obvious causes, relation to the vaccination, and other similar reports, we assumed that the trigeminal neuralgia was a complication of the vaccination. Hospital treatment consisted of oxcarbazepine, dexamethasone and pregabalin. Treatment was successful, with transient episodes of exacerbation. Six months after the onset of the disorder the patient remains without pain. We believe that the presented case supports the possibility of trigeminal neuralgia occurring in relation to the Pfizer BioNTech COVID-19 vaccine administration. Additional reports may further contribute to establishing a certain link.
Malaria remains one of the most common human infections worldwide. In endemic areas, malaria is a leading cause of morbidity and mortality and it imposes significant socioeconomic burdens on the people affected. Monocytes are part of the immune system controlling parasite burden and protecting the host against malaria infection. Monocytes play their protective roles against malaria via phagocytosis, cytokine production and antigen presentation. Though monocytes are crucial for clearance of malaria infection, they have also been shown to cause adverse clinical outcomes. In this review, we discuss recent findings regarding the role of monocytes in malaria via mechanisms such as parasite detection and clearance, pro-inflammatory activities, and activation of other immune components. We also highlight the role of different monocyte subsets, and other myeloid cells that are involved in malaria infection. However, more investigations are required in order to explore the exact roles of these monocytes in malaria infection.
Immune diseases are caused by the imbalance of immune regulation. This imbalance is regulated by many factors, both negative and positive. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is a member of leukocyte immunoglobulin-like receptors (LILRs). LILRs are expressed constitutively on the surface of multiple immune cells which associate with membrane adaptors to signal through multi- ple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or immunoreceptor tyro-sine-based activation motifs (ITAMs). Through ITIM, LILRB4 could recruit the src homology domain type-2-containing tyrosine phosphatase 1 or 2 (SHP-1 or SHP-2) into the cell membrane. In addition, many factors can induce the expression of LILRB4, such as vitamin D, interferon and so on. Studies have demonstrated that LILRB4 had a negative regulatory role in various of immune diseases. The present review intends to expound the structure and function of LILRB4, as well as its regulators and receptors in the immune cells, so as to provide a theoretical basis for immune disease therapy.
Steroid resistance is a common condition occurring in children with nephrotic syndrome. Until now, over 50 genes involved in steroid-resistant nephrotic syndrome (SRNS) pathogenesis have been identified, among which the most prevalent are NPHS1, NPHS2, CD2AP, and PTPRO. The patterns of inheritance of SRNS are autosomal recessive, autosomal dominant, or mitochondrial, and tissues of those patients show focal segmental glomerulosclerosis (FSGS) signs in histopathological image analysis. We present a case of a 6-year-old girl who was admitted to the pediatric nephrology department due to nephrotic range proteinuria and edema of the lower leg. We started therapy with prednisone at a dose of 45 mg (60 mg/m2), enalapril as a nephroprotection, and antihistamines as an additional treatment. During in-patient treatment, we detected increased blood pressure. Due to persistent proteinuria in spite of 6-week treatment with steroids at the maximal dose, we confirmed disease resistance to steroids. Additionally, FSGS signs were confirmed in kidney biopsy samples. After genetic screening for SRNS and detection of the rare gene mutation NUP93 we reduced prednisone but maintained nephroprotective treatment and administered cyclosporin A. The girl remains currently under the care of nephrologists with normal arterial blood pressure, trace proteinuria in follow-up examination, and normal kidney function. NUP93 mutation is extremely rare; therefore few cases have been described to date. The onset of the symptoms in all pediatric patients appeared before the age of 8 and they developed end stage kidney disease (ESKD). They might manifest symptoms from the other systems.
Introduction: Asthma is a common respiratory disease. Theophylline combined with inhaled corticosteroids (ICS) is a promising therapy for asthma. This study explored the therapeutic effects of ICS combined with theophylline on moderate and severe asthma patients and T lymphocyte subsets (CD3+CD8+ T cells) in peripheral blood.
Material and methods: A total of 202 moderate and severe asthma patients were selected, with 101 treated with theophylline combined with ICS and 101 treated with ICS alone as controls. Lung function [forced expiratory volume within 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)] were tested using a spirometer. Asthma symptom control was evaluated by asthma control tests (ACT). The life quality was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). The number and percentage of CD3+ T, CD3+CD4+ T and CD3+CD8+ T cells in peripheral blood mononuclear cells were assessed by flow cytometry. The correlation between CD3+CD8+ T cells and lung function and asthma control of patients after combination therapy was analyzed by Pearson correlation analysis.
Results: Compared with moderate and severe patients treated with ICS alone, theophylline improved the efficacy of ICS. Theophylline combined with ICS decreased IL-4 and IL-6 levels, and CD3+ T and CD3+CD8+ T cell number and percentage. After combined treatment, CD3+ CD8+ T cells in peripheral blood of patients were positively correlated with lung function and negatively correlated with asthma control.
Conclusions: The additional use of theophylline improved the efficacy of corticosteroids in asthma patient treatment and reduced inflammation level and CD3+ T and CD3+CD8+ T cell contents in peripheral blood.