Cellular Immunity In Patients Research Articles

Influence of stress on cellular immunity in patients with autoimmune thyroid pathology

Influence of stress on cellular immunity in patients with autoimmune thyroid pathology

Effect of acupuncture anesthesia on inflammatory response and cellular immunity in patients with osteoporotic fractures.

Osteoporotic vertebral compression fractures (OVCFs) occur frequently in the elderly, with percutaneous vertebroplasty (PVP) being the major clinical treatment at present. How to improve the patient's surgical cooperation while ensuring surgical safety is the focus of clinical research. This study explores the influence of acupuncture anesthesia (AA) on the safety, inflammatory response, and cellular immunity of OVCF patients undergoing PVP, which may provide a more reliable safety guarantee for future treatment of OVCFs. The results showed that patients using AA had lower postoperative Visual Analogue Scale (VAS) scores and incidence of postoperative adverse reactions, a smaller anesthetic dosage, but an extended duration of anesthesia; moreover, the postoperative inflammatory response was markedly alleviated and the stability of T lymphocyte subsets was obviously enhanced. Therefore, AA has high clinical application value in PKP treatment of OVCFs in the future.

Activity of cellular immunity in patients with nutrition-dependent diseases (obesity, type 2 diabetes)

The purpose of the study is to analyze the indicators of cellular immunity in patients with obesity (OB) and type 2 diabetes mellitus (DM2). The study included 15 patients with DM2 (DM2 group), body mass index (BMI) 37.36±1.12 kg/m2, 12 patients with OB (OB group), BMI – 38.12±1.51 kg/m2 and 15 practically healthy individuals (comparison group – GС): BMI 23.5±0.15 kg/m2. The study was performed on a flow cytometer FC-500 (Beckman Coulter, USA) using double combinations of monoclonal antibodies (Beckman Coulter – Immunotech SAS, France). The percentage indicators of the T cell population were assessed, such as total number of T lymphocytes (CD3+), number of T helper cells (CD3+CD4+), cytotoxic T lymphocytes (CD3+CD8+), natural killer cells – NK cells (CD3-CD16+CD56+), natural killer cells with the properties of T lymphocytes – NKT cells (CD3+CD16+CD56+) and B cell population (CD19+) lymphocytes, as well as the relative content of lymphocytes carrying activation markers (CD3+HLA-DR+, CD3+CD25+), and apoptosis marker antigen CD45+CD95+. The relative content of B lymphocytes and T lymphocytes in the peripheral blood of the examined individuals did not have statistically significant differences. In patients in the DM2 and OB groups, there was a tendency (p 0.1) towards an increase in the relative content of T helper cells and a significant (p 0.05) decrease in the percentage of T cytotoxic lymphocytes relative to GC. This redistribution of lymphocyte subpopulations led to a significant (p 0.05) increase in the IRI value (arbitrary units): DM2 – 2.87±0.58; OB – 2.30±0.33 vs GC – 1.62±0.15. The relative content of NK cells and NKT cells in the peripheral blood of the examined individuals did not have a statistically significant difference in the magnitude of the indicators. A statistically significant (p 0.05) increase in the relative content of T lymphocytes expressing the activation marker HLA-DR (CD3+HLA-DR+) was found in patients in the DM2 and OB groups relative to GC [(%) DM2 – 7.95±0, 81; OB – 6.54±0.24; GC – 4.01±0.91] and a significant (p 0.05) increase in the percentage of CD45+CD95+ lymphocytes in patients with OB and DM2 relative to GC [(%) DM2 – 5.84±0.68; OB – 5.16±0.89; GC – 2.78±0.34]. The results obtained indicate the presence of meta-inflammation in patients with DM2 and OB.

A prognostic model for SARS-CoV-2 breakthrough infection: Analyzing a prospective cellular immunity cohort

BackgroundFollowing the COVID-19 pandemic, studies have identified several prevalent characteristics, especially related to lymphocyte subsets. However, limited research is available on the focus of this study, namely, the specific memory cell subsets among individuals who received COVID-19 vaccine boosters and subsequently experienced a SARS-CoV-2 breakthrough infection. MethodsFlow cytometry (FCM) was employed to investigate the early and longitudinal pattern changes of cellular immunity in patients with SARS-CoV-2 breakthrough infections following COVID-19 vaccine boosters. XGBoost (a machine learning algorithm) was employed to analyze cellular immunity prior to SARS-CoV-2 breakthrough, aiming to establish a prognostic model for SARS-CoV-2 breakthrough infections. ResultsFollowing SARS-CoV-2 breakthrough infection, naïve T cells and TEMRA subsets increased while the percentage of TCM and TEM cells decreased. Naïve and non-switched memory B cells increased while switched and double-negative memory B cells decreased. The XGBoost model achieved an area under the curve (AUC) of 0.78, with an accuracy rate of 81.8 %, a sensitivity of 75 %, and specificity of 85.7 %. TNF-α, CD27-CD19+cells, and TEMRA subsets were identified as high predictors. An increase in TNF-α, cTfh, double-negative memory B cells, IL-6, IL-10, and IFN-γ prior to SARS-CoV-2 infection was associated with enduring clinical symptoms; conversely, an increase in CD3+ T cells, CD4+ T cells, and IL-2 was associated with clinical with non-enduring clinical symptoms. ConclusionSARS-CoV-2 breakthrough infection leads to disturbances in cellular immunity. Assessing cellular immunity prior to breakthrough infection serves as a valuable prognostic tool for SARS-CoV-2 infection, which facilitates clinical decision-making.

The Relationship between Serum Zonulin and Innate Immunity in Patients with Inflammatory Bowel Disease

The aim of the study was to investigate the relationship between the serum zonulin and the cellular immunity in patients with ulcerative colitis (UC) and Crohn’s disease (CD). The study included 97 patients, 13 (13.4%) patients with CD and 84 (86.6%) patients with UC. The concentration of zonulin in the serum was studied using the ELISA kits. The investigation of the circulated leukocyte subpopulation was carried out through flow cytometry. The functional activity of the circulating neutrophils was studied using the absorption capacity of the monodisperse polystyrene latex particles and indicators of oxygen-dependent metabolism in the nitroblue tetrazolium test. The serum zonulin concentration in CD patients was significantly higher compared with UC patients (p = 0.003). The zonulin concentration directly correlated with the functional activity of the circulating neutrophils. Patients with a zonulin concentration > 472.4 pg/mL had a significantly higher number of band neutrophils (p = 0.0104), CD3+CD8+ cells (p = 0.0212), NK cells (p = 0.0161), and lower–CD19+ cells (p = 0.0034). Among the IBD patients, zonulin was associated with IBD severity. An increase in the serum concentration of zonulin was associated with an increase in the functional activity of circulating neutrophils and an increase in the number of CD3+CD8+ cells, NK cells, and a decrease in the number of CD19+ cells.

Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy exhibits remarkable efficacy against refractory or relapsed multiple myeloma (RRMM); however, the immune deficiency following CAR-Ts infusion has not been well studied. In this study, 126 patients who achieved remission post-CAR-Ts infusion were evaluated for cellular immunity. Following lymphodepletion (LD) chemotherapy, the absolute lymphocyte count (ALC) and absolute counts of lymphocyte subsets were significantly lower than baseline at D0. Grade ≥ 3 lymphopenia occurred in 99% of patients within the first 30days, with most being resolved by 180days. The median CD4+ T-cell count was consistently below baseline and the lower limit of normal (LLN) levels at follow-up. Conversely, the median CD8+ T-cell count returned to the baseline and LLN levels by D30. The median B-cell count remained lower than baseline level at D60 and returned to baseline and LLN levels at D180. In the first 30days, 27 (21.4%) patients had 29 infections, with the majority being mild to moderate in severity (21/29; 72.4%). After day 30, 44 (34.9%) patients had 56 infections, including 20 severe infections. One patient died from bacteremia at 3.8months post-CAR-Ts infusion. In conclusion, most patients with RRMM experienced cellular immune deficiency caused by LD chemotherapy and CAR-Ts infusion. The ALC and most lymphocyte subsets gradually recovered after day 30 of CAR-Ts infusion, except for CD4+ T cells. Some patients experience prolonged CD4+ T-cell immunosuppression without severe infection.

The effect of vitamin D deficiency on the cellular immunity of patients in the early stage of COVID-19 disease

COVID-19 is a disease with a wide range of symptoms and severity due to the ability of SARS-COV-2 to infect many kinds of tissues and organs in the patient's body. The disease begins commonly with symptoms of respiratory tract infection that may be mild and limited or progress to severe infection with fatal consequences. Vitamins play essential roles in our biology, including supporting immunity. Vitamin D deficiency became a public problem, and its effect as an immunomodulator in many viral infections was approved. This study investigated the effect of vitamin D deficiency on cellular immunity, especially lymphocytes, in COVID-19 patients when the disease is in its early stages. Tests were done for the complete blood count lymphocyte proliferation assay in response to non-specific mitogen and immunoglobulin levels. The study revealed no significant effect of vitamin D deficiency on the T-lymphocyte activation at the early stage of the infection. Vitamin D deficient patients have lower immunoglobulin levels, necessitating vaccination against COVID-19 infection. Keywords: COVID-19, lymphocyte proliferation, mitotic index, vitamin D

The Immunomodulatory Effect of Various Anaesthetic Practices in Patients Undergoing Gastric or Colon Cancer Surgery: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Gastric and colorectal carcinomas are associated with increased mortality and an increasing incidence worldwide, while surgical resection remains the primary approach for managing these conditions. Emerging evidence suggests that the immunosuppression induced by the chosen anaesthesia approach, during the perioperative period, can have a significant impact on the immune system and consequently the prognosis of these patients. This systematic review aims to comprehensively summarize the existing literature on the effects of different anaesthesia techniques on immune system responses, focusing on cellular immunity in patients undergoing the surgical removal of gastric or colorectal carcinomas. There is no meta-analysis investigating anaesthesia's impact on immune responses in gastric and colorectal cancer surgery. Anaesthesia is a key perioperative factor, yet its significance in this area has not been thoroughly investigated. The clinical question of how the anaesthetic technique choice affects the immune system and prognosis remains unresolved. Major electronic databases were searched up to February 2023 to May 2023 for relevant randomized controlled trials (RCTs). The study protocol has been registered with Prospero (CRD42023441383). Six RCTs met the selection criteria. Among these, three RCTs investigated the effects of volatile-based anaesthesia versus total intravenous anaesthesia (TIVA), while the other three RCTs compared general anaesthesia alone to the combination of general anaesthesia with epidural anaesthesia. According to our analysis, there were no significant differences between TIVA and volatile-based anaesthesia, in terms of primary and secondary endpoints. The combination of general anaesthesia with epidural analgesia had a positive impact on NK cell counts (SMD 0.61, 95% CI 0.28 to 0.94, I2 0.0% at 24 and 72 h after the operation), as well as on CD4+ cells (SMD 0.59, CI 95% 0.26 to 0.93, I2 0.0%). However, the CD3+ cell count, CD4+/CD8+ ratio, neutrophil-to-lymphocyte ratio (NLR), IL-6 and TNF-α levels remained unaffected. The combination of epidural analgesia and general anaesthesia can potentially improve, postoperatively, the NK cell count and CD4+ cell levels in gastric or colon surgery patients. However, the specific impact of TIVA or volatile-based anaesthesia remains uncertain. To gain a better understanding of the immunomodulatory effects of anaesthesia, in this particular group of cancer patients, further well-designed trials are required.

The restorative effect of immunoglobulin G on indicators of cellular immunity in patients with co-infection drug-resistant tuberculosis/HIV with a CD4 lymphocyte cоunt from 200 to 50 cells/μL

Objective — to study the restorative effect of immunoglobulin G (IgG) in patients on indicators of cellular immunity in patients with drug-resistant tuberculosis (DR-TB)/HIV co-infection at the level of CD4+ lymphocytes from 200 to 50 cells/μL. Materials and methods. The study involved 52 patients aged 20 to 55 years, the average age was (37.2 ± 7.8) years. All patients were HIV-positive with laboratory-confirmed DR-TB with mycobacterium resistance to first- and second-line drugs. Patients on DR-TB/HIV were divided as follows: Group 1 (cont­rol) — 26 patients with DR-TB/HIV with the CD4 lymphocyte count from 200 to 50 cells/μL, who received standard treatment with second-line antimycobacterial therapy (AMBT) and antiretroviral therapy (ARVT); Group 2 (basic) — 26 patients with DR-TB/HIV with a CD4 lymphocyte count from 200 to 50 cells/μL, who also received standard treatment of second-line AMBD and ARVT, with the addition of complex therapy with intravenous IgG. Results and discussion. In patients of Group 2, at the end of the 20th month of treatment, the normalization of T-helpers level was noted in 69.2 % of people, which reached the average values of (830.0 ± 15.2) cells/μL, with an increase to a subnormal level (408,0 ± 1.6) cells/μL in 30.8 % of patients (p < 0.05). Normalization of the T-helpers indicator in Group 1 was noted on the 20th month only in 42.3 % of people, and it amounted to (670.0 ± 14.5) cells/μL (р < 0.05). The relative (percentage) level of the T-helpers indicator in the 20th month reached normal values in 61.5 % (р < 0.05) of patients of Group 2, among patients of Group 1 — in 34.6 % of people (р < 0.05 ). The absolute number of T-suppressors at the end of the 20th month decreased to the norm in 76.9 % of patients and 46.2 % of patients in Groups 2 and 1, respectively (p < 0.05). In patients of Group 2, on the 20th month of treatment, the physiological level of the T-suppressors indicator (19—35) % was reached in 65.4 % of cases (р < 0.05); in Group 1, the normal level was registered in 38.5 % of patients (p < 0.05). The CD4+/CD8+ Ratio was below the norm in 100 % of patients of Group 1 during 14 months inclusive, and only on the 20th month it reached the norm in 23.1 % of patients (p < 0.05). Group 2 patients had normalization in 57.7 % of cases at the 20th month (р < 0.05). Conclusions. The additional use of intravenous IgG in the complex treatment of patients with DR-TB/HIV contributed to a faster recovery of the cellular link of immunity, which makes it possible to prescribe antiretroviral therapy to patients with DR-TB/HIV at an earlier time, prevent the development of systemic inflammation and improve the prognosis for survival.

Interrelations between viral load and cellular immunity in patients with COVID-19 of varying severity

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19.The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relation-ship between viral load and changes in the parameters of the cellular component of the immune system.A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene. A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined.We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+).Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve early assessment of clinical condition in the patients with COVID-19. Changes in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.

The production of pro-inflammatory cytokines and the state of cellular immunity in patients with pulmonary tuberculosis with and without relapse

The purpose of the study was to conduct a comparative study of the synthesis of pro-inflammatory cytokines, the state of cellular immunity, free radical oxidation reactions and antioxidant protection in patients with pulmonary tuberculosis with and without relapse. Material and methods. The study was carried out on two groups of patients: the first group basic which included 39 patients with relapsed pulmonary tuberculosis (TBR); 2nd control group 39 patients with non-relapsed pulmonary tuberculosis (TB). Pro-inflammatory cytokines (TNF-α, IL-2 IL-6), CD-3 lymphocyte content, lymphocyte blast transformation response to phytohemagglutinin and tuberculin, NBT-test, AOPP, SOD, and catalase were determined in patients of both groups and healthy people. Results. In patients with tuberculosis with relapses, compared with patients without relapses, complaints of cough and dyspnea were more often presented, a longer duration of hospitalization, late abacillation. In patients with relapses, a pronounced suppression of the functional and specific activity of lymphocytes and neutrophils was noted, which is confirmed by high levels of lipid peroxidation (Advanced Oxidation Protein Products AORP) and low levels of the antioxidant system (SOD and catalase). The high content of pro-inflammatory cytokines in patients with relapses indicates a higher activity of the inflammatory process in these patients and corresponds to a low blast formation rate for both phytohemagglutinin and tuberculin. Conclusion. Сhanges in the content of pro-inflammatory cytokines, the state of cellular immunity and the characteristics of reactions of free radical oxidation and antioxidant protection indicate a higher activity of the inflammatory process in patients with pulmonary tuberculosis with relapses compared to patients without relapses, which led to a longer duration of hospitalization, late abacillation.

Effect of Remimazolam Combined with Propofol Anesthesia on Perioperative Cellular Immunity in Patients Undergoing Laparoscopic Ovarian Cyst Surgery

Effect of Remimazolam Combined with Propofol Anesthesia on Perioperative Cellular Immunity in Patients Undergoing Laparoscopic Ovarian Cyst Surgery

Prevalence of SARS-CoV-2 Cellular and Humoral Immunity Amongst Patients on Dialysis After the First Vaccination Campaign

Background: Immunisation remains critical in prevention of serious COVID-19 infection. This study aimed to characterise the prevalence of humoral and cellular immunity in patients on maintenance dialysis in a nephrology centre 8 months after vaccination onset. Methods: Real-world single-centre prevalence cross-sectional study enrolling patients on peritoneal and haemodialysis. Humoral response was measured as specific IgG (anti-spike protein receptor-binding domain IgG) and cellular response as T cell reactivity through interferon γ quantification as response to antigen. Results: Of the 86 patients enrolled, 79.4% and 84.1% showed humoral and cellular immunity, respectively. Anti-spike protein receptor-binding domain IgG correlated with specific T cell reactivity (ρ=0.58; p<0.001). Vaccinated patients with associated high comorbidity burden and low serum albumin were at risk of absent immunity (p<0.05). Conclusion: The prevalence of humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 in vaccinated Portuguese patients on maintenance dialysis is high. High comorbidity burden and low serum albumin are risk factors for absent immune response.

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer.

CURRENT ISSUES OF VITAMIN D IN JUVENILE IDIOPATHIC ARTHRITIS

Background. Children with juvenile idiopathic arthritis (JIA) represent a special cohort of patients with chronic somatic pathology, characterized by severe damage to the musculoskeletal system and other vital organs and systems, which is associated with immune and metabolic changes in the body. Data regarding the provision of vitamin D (VD) in patients with JIA and the significance of its deficiency in the initiation, activation of the autoimmune process, the prognosis of the course of the disease, the risk of developing complications and the effectiveness of protocol therapy are contradictory. Objective. To investigate the body's supply of vitamin D in patients with juvenile idiopathic arthritis with the determination of the trigger factors of its deficiency, the assessment of the immune status and changes in the nucleotide sequence in the genes of innate immunity. Materials and methods. Research was conducted during 2016-2021 at the Institute in 119 patients with JIA aged 6 to 12 years. The concentration of 25OHD was determined in blood serum using commercial Vitamin D3 kits (Screeningkit, Switzerland). Immunological studies were performed by flow cytofluorimetry and enzyme immunoassay. For panel sequencing of 407 genes regulating immune functions, high-throughput panel exome sequencing was used on Illumina's HiSeq machine (made in the USA) at the Invitae laboratory (USA). The obtained digital data were processed by methods of statistical analysis using the Microsoft Excel computer package. Results. A high frequency of low supply of vitamin D in patients with JIA was revealed: vitamin D insufficiency was diagnosed in 96 (80.6 %), and its deficiency - in 38 (31.9 %) children. The lowest levels of 25ОНD concentration in blood serum (less than 15 ng/ml) are observed in patients with stage II–III disease activity, especially at the beginning of the pathological process. Vitamin D deficiency (DVD) was associated with the activity and severity of the clinical course, frequent exacerbation of the joint syndrome, the expressiveness of changes in the humoral and cellular immunity of patients. The main risk factors for reducing the body's supply of WD in patients with JIA have been determined, which must be taken into account during their observation and treatment. High activity of JIA in patients with VD deficiency in the body was associated with a significant increase in the number of CD3+ T-cells, CD3+CD4+ helper-inducer T-cells, activated HLA-DR+/CD3+ T-cells, ESR, C-reactive protein concentration (CRP), tumor necrosis factor (TNF), circulating immune complexes (CIC), immunoglobulins, which allows considering DWD as a likely predictor of severe and prognostically unfavorable course of rheumatic disease. Nucleotide sequence changes in the NOD2 gene were detected in 18.1 % of patients with JIA: c.2104C>T (p.Arg702Trp), c.3019dupC (p.Leu1007Profs*2). The of variable changes in patients with JIA is statistically significantly different from the population [VSh = 11.39; 95 % CI (2.39-54.22)]. DVD was detected in all children with mutations in the NOD2 gene – (17.2 ± 3.29) ng/ml, and in children without changes in the nucleotide sequence - in 23 (85.1 %) children [SS = 0.097; DI (0.03-0.31)], the concentration of VD is significantly higher - [(26.68 ± 2.34) ng/ml, p = 0.026]. Conclusions. The conducted studies confirm the presence of a decrease in the body's supply of vitamin D in patients with JIA, which is associated with a high activity of the pathological process and pronounced immunological changes in the body, which allows us to consider its deficiency as a likely predictor of a severe and prognostically unfavorable course of the disease. It has been proven that the concentration of vitamin D in JIA is higher in patients without changes in the nucleotide sequence in the NOD2 gene, which must be taken into account when predicting and evaluating the body's response to the treatment of juvenile arthritis. Key words: juvenile idiopathic arthritis, vitamin D, immunological status, genetic sequencing, children.

SARS-CoV-2 vaccine-induced humoral and cellular immunity in patients with hematologic malignancies

Patients with hematologic conditions have a higher risk of severe COVID-19 and COVID-19-related death. This is related to immune deficiencies induced by hematologic conditions and/or the treatment thereof. Prospective vaccine immunogenicity studies have demonstrated that in the majority of patients, a 3-dose COVID-19 vaccination schedule leads to antibody concentrations comparable to levels obtained in healthy adults after a 2-dose schedule. In B cell depleted patients, humoral responses are poor, however vaccination did induce potent cellular immune responses. The effect of 3-dose vaccination schedules and COVID-19 booster vaccinations on the protection of patients with hematologic malignancies against severe COVID-19 and COVID-19 related death remains to be confirmed by population-based vaccine effectiveness studies.

Effects of the BTN162b2 mRNA COVID-19 vaccine in humoral and cellular immunity in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), the most common leukemia in the western countries, is characterized by immunosuppression due to disease itself and cytotoxic treatments. Since the beginning of COVID‐19 pandemic, patients with CLL appear to be a vulnerable population. In addition, phase III mRNA vaccine trials did not provide information about the efficacy in immunocomprised population. In CLL, the antibody‐mediated response to SARS‐CoV‐2 vaccine is impaired. The goal of this study was to evaluate the effects of SARS‐CoV‐2 vaccination on humoral immune response and on cellular immunity in CLL patients. Humoral immune response to BNT162b2 messenger RNA COVID‐19 vaccine was evaluated in 44 CLL patients comprising 20 treatment‐naïve, 14 under treatment with ibrutinib and 10 in follow‐up after completion of therapy. A positive serological response to SARS‐CoV‐2 vaccination with IgG titers higher than 13 UA/ml was detected in 54.6% of CLL patients with a higher response in patients who obtained remission after treatment. Reduced antibody response was detected in patients under ibrutinib treatment. T‐cell response to overlapping pool of peptides representing the spike region was assessed in paired CLL samples collected before and after 1 month from the second dose of COVID‐19 vaccine in treatment‐naïve and ibrutinib‐treated CLL patients using cytokine secretion assay. Both CD3+ CD4+ and CD3+ CD8+ T cells are able to mount a cellular response to spike peptides with secretion of IFNγ and TNFα before and after vaccination in both treatment naïve and ibrutinib‐treated patients and this cellular immune response is independent by COVID‐19 vaccination. Collectively, T cell response to spike peptides appeared more blunted in CLL patients under treatment with ibrutinib compared to untreated ones. Our study supports the need for optimization of vaccination strategy to achieve an adequate immune response keeping strict preventive measures by CLL patients against COVID‐19.

Advances in the cellular immunological pathogenesis and related treatment of primary ovarian insufficiency.

To describe the immunological mechanism in the pathogenesis of premature ovarian insufficiency (POI), summarize the alternations in humoral immunity and cellular immunity in patients with POI, and review some associated treatment methods based on these immunological changes. Symptoms of patients with POI are similar to that of menopause, such as amenorrhea, anovulation, early depletion of the ovarian reserve, decreased estrogen, and elevated follicle-stimulating hormone (FSH) levels. Therefore, most previous research has focused on finding ovary-related antibodies. In recent years, advances in the field of immunology have increased our understanding of the pathogenic mechanism of POI, which includes changed levels of cytokines and immunological cells especially Tregs cells and Th17 cells. Based on these advances, many associatedtreatment methods including DHEA supplementation, Traditional Chinese Medicine, adoptive transfer of Treg cells and stem cell transplantation have become research hotspots. This review focuses on the current literature regarding alterations in cellular immunity in patients with POI, as well as the role in the pathogenesis of POI, and summarizes treatment methods based on these immunological alternations, which have a great application potential in the clinical practice.

Effects of ibrutinib on T-cell immunity in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL), a highly heterogeneous B-cell malignancy, is characterized by tumor microenvironment disorder and T-cell immune dysfunction, which play a major role in the proliferation and survival of CLL cells. Ibrutinib is the first irreversible inhibitor of Bruton’s tyrosine kinase (BTK). In addition to targeting B-cell receptor (BCR) signaling to kill tumor cells, increasing evidence has suggested that ibrutinib regulates the tumor microenvironment and T-cell immunity in a direct and indirect manner. For example, ibrutinib not only reverses the tumor microenvironment by blocking cytokine networks and toll-like receptor signaling but also regulates T cells in number, subset distribution, T-cell receptor (TCR) repertoire and immune function by inhibiting interleukin-2 inducible T-cell kinase (ITK) and reducing the expression of inhibitory receptors, and so on. In this review, we summarize the current evidence for the effects of ibrutinib on the tumor microenvironment and cellular immunity of patients with CLL, particularly for the behavior and function of T cells, explore its potential mechanisms, and provide a basis for the clinical benefits of long-term ibrutinib treatment and combined therapy based on T-cell-based immunotherapies.

Cellular immunity in patients with COVID-19: molecular biology, pathophysiology, and clinical implications

The COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. From the viewpoint of factors critical to contain the virus, the neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to acknowledge that it is the level of the virus-specific T cell and B cell response that forms a basis for an effective neutralizing antibody response. T cell responses develop early and correlate with the protection, but they are relatively attenuated in the severe disease, in part due to lymphopenia. Understanding the role of different T cell subpopulations in the protection or the COVID-19 pathogenesis is critical to the prevention and treatment. The expression profile of different T cell subpopulations varies with the COVID-19 severity and is associated with the degree of T cell responses and the disease outcome. The structural changes in the genome, transcriptome, and proteome of SARS-CoV-2 promote the emergence of new variants of the virus and can reduce its interaction with antibodies and result in avoiding the neutralization. There is a strong correlation between the number of virus-specific CD4 T cells and neutralizing IgG antibody titers against SARS-CoV-2. During the primary viral infection, there is a wide variation in the cellular and humoral immune responses, patients with severe and prolonged symptoms showing highly imbalanced cellular and humoral immune responses. This review focuses on the generation and clinical significance of cellular immunity in the protection against severe acute infection and reinfection, as well as the potential involvement of seasonal coronavirus-specific cross-reactive T cells in response to SARS-CoV-2.