scholarly journals Vaccination Against Diphtheria and Tetanus as a Way to Activate Adaptive Immunity in Children with Solid Tumors

2021 ◽  
Vol 12 ◽  
Author(s):  
Mikhail Petrovich Kostinov ◽  
Nelli Kimovna Akhmatova ◽  
Svetlana Victorovna Karpocheva ◽  
Anna Egorovna Vlasenko ◽  
Valentina Borisovna Polishchuk ◽  
...  

Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic.

2021 ◽  
Vol 8 (3) ◽  
pp. 167-172
Author(s):  
Edvard A. Berg ◽  
Alfiya G. Yashchuk ◽  
Il’nur I. Musin ◽  
Raisa A. Naftulovich ◽  
Elena M. Popova

AIM: The study aimed to investigate the cellular immunity in patients with placental disposition. MATERIALS AND METHODS: A prospective study analyzed birth histories and clinical and laboratory parameters of 10 patients with placental disposition. The cellular immunity status was determined by analyzing lymphocytes with a cluster of differentiation (CD), including CD3+, CD4+, CD8+, CD16+56, CD3-СD8+, TNK, and CD38+8+. Obtained data were analyzed statistically. RESULTS: Patients were 32.0 (29.0; 36.0) years old. As regards reproductive history, 60.0% had a history of three pregnancies, 20% had two pregnancies, 10% had their first pregnancy, and 10% had their fourth pregnancy. Moreover, placenta dispositions most often occurred at the second pregnancy in 70.0%, at the third pregnancy in 20.0%, and first pregnancy in 10%. In terms of cell immunity in comparison with normal indicators, the relative number of natural killer cells (CD16+56+), including activated CD3-СD8+, tended to increase. A relative increase in cytotoxic T-lymphocytes (СD8+) was found against the background of lower number of T-helper cells, along with general immunodeficiency (immunoregulatory index in the absolute number of women was less than 1.5). CONCLUSIONS: Further investigation of cellular immunity in women with placental pathology is relevant to detect additional pathogenetic mechanisms of the development of obstetric complications.


Author(s):  
Guang Chen ◽  
Di Wu ◽  
Wei Guo ◽  
Yong Cao ◽  
Da Huang ◽  
...  

AbstractBackgroundSince late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported.MethodsIn this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases.ResultsOf the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (0.7 × 10□/L) than moderate cases (1.1 × 10□/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 × 106/L) than moderate cases (676.5, 359.2 and 272.0 × 106/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%).ConclusionThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.


2015 ◽  
Vol 72 (11) ◽  
pp. 1039-1043 ◽  
Author(s):  
Dragana Tadic ◽  
Olivera Markovic ◽  
Nada Kraguljac-Kurtovic ◽  
Olika Drobnjak-Tomasek

Introduction. Good?s syndrome is a rare cause of adultonset immunodeficiency associated with thymoma. Good?s syndrome should be considered in patients older than 40 years with the history of frequent infections. An abnormal immunoglobulin profile needs further investigation and flow cytometry which is crucial for establishing the diagnosis of Good?s syndrome. Case report. We present a 56- year-old men with Good?s syndrome diagnosed after a twoyear history of recurrent infections. Examination of immune status of the patient showed decreased serum levels of all immunoglobulins. Flow cytometry of peripheral blood lymphocyte revealed markedly reduced peripheral B cells, CD4 T-cell lymphopenia, inverted CD4/CD8 T-cell-ratio 0.37 (CD4 - 20.82%, CD8 - 70.7%). Analysis of the subpopulations of T-lymphocytes showed relative increasing ?? T cell receptor (TCR) T lymphocytes. Computed tomography scan of the chest showed a mediastinal mass compatible with thymoma of the diameter of 40 mm. After initiation of intravenous immunoglobulins the patient was in the good clinical condition and without bacterial complications. As the patient refused the operative treatment we continued to control the mediastinal tumor mass which did not increase during a 3-year follow-up. Conclusion. The presented patient had a typical immunological finding for Good?s syndrome, but also the increase in ?? TCR T-lymphocyte subpopulation for which it is difficult to determine whether this is pathogenetic or secondary reactive event.


2020 ◽  
Vol 22 (1) ◽  
pp. 157-164
Author(s):  
O. V. Makarova ◽  
E. A. Postovalova ◽  
Yu. Gao ◽  
M. T. Dobrynina

We studied sex differences lymphocytes subpopulations of peripheral blood in adult C57Bl/6 mice during acute and chronic colitis, induced with 1% DSS. We measured subpopulations of lymphocytes with flow cytometry. We showed that in the control group the female mice had statistically significantly higher values of the relative number of regulatory and cytotoxic T lymphocytes comparing to the males. During acute colitis the females showed an increase in the relative number of Thelpers and a decrease of cytotoxic Tlymphocytes, which reflects the activation of immune response. The males had a decrease in the absolute number of leukocytes, lymphocytes and cytotoxic and regulatory T lymphocytes, probably because of an increase in migration of these cells to the inflammation locus and local lymph nodes. In chronic colitis the females had a decrease in the absolute number of leukocytes, lymphocytes, T helpers, cytotoxic T lymphocytes and B lymphocytes when comparing with acute colitis. During chronic colitis the males had a decrease in the absolute number of T helpers and B lymphocytes but an increase of regulatory T cells in comparison with the control group; in comparison with acute colitis the males with chronic colitis had higher relative and absolute number of regulatory T cells. The increase of T regulatory lymphocytes is due to an increase in their proliferation rate in the thymus and increase of their migration to the inflammatory locus – the colon. Future clinical studies may be based on these results, which show that the treatment of colitis, especially with immunotropic agents, must take sex differences into account.


2020 ◽  
Vol 9 (3) ◽  
pp. 54-63
Author(s):  
N. S. Fedorovskaya ◽  
L. M. Zheleznov ◽  
S. V. Petrov ◽  
V. B. Zaitsev

The aim of the study was to characterize the immunomorphological processes in the spleen of patients with immune thrombocytopenia depending on the form of the disease and the response to splenectomy. Material and methods. The study included the spleens of 50 patients with immune thrombocytopenia, including 32 women (64%) and 18 men (35%). The median age was 38.0 (22.8; 52.0) years. Depending on the form of the disease, all patients with immune thrombocytopenia were divided into three groups: first diagnosed disease (n=12); persistent form (n=20); and chronic form (n=18). All cases of immune thrombocytopenia were divided into two subgroups: 1 (n=32) – patients who were in remission after splenectomy; 2 (n=18) – people with refractory disease after splenectomy The comparison group was represented by spleens autopsy material of 20 people who had no history of blood system and liver diseases, or other pathology. The median age was 39 (27; 65) years. Histological, immunohistochemical, and morphometric methods were used to study the size of the red and white spleen pulps, as well as their cellular composition.Results. In patients with immune thrombocytopenia who responded to splenectomy, the spleen morphology was characterized as corresponding to stages I–II of the immune response. In the subgroup with a refractory course of the disease and in patients with a persistent form, the condition of the spleen corresponded to stages II–III of the immune response, which indicated a longer or aggressive course of the disease. Reducing the size of the periarterial lymphoid muffs, regardless of the response to splenectomy in relation to the comparison group (p<0.05), reflects the pathogenesis of the disease and presents the effect of immunosuppressive therapy on T-cell area of white pulp. Changes in the cell composition of the spleen in patients with immune thrombocytopenia were characterized by an increase in the relative and absolute number of B and T lymphocytes in the white and red pulps, macrophages (CD68+) and dendritic cells (CD35+, S100+). An increase in the content of lymphoid elements expressing CD4+ in white and red pulps, as well as CD8+ T-lymphocytes in the red pulp indicates a multifactorial development of autoimmune disorders in this disease. A significant increase in the number of cytotoxic CD8+ T cells and CD68+ macrophages in the red pulp in patients with refractory course of immune thrombocytopenia compared to those who responded to splenectomy (p<0.05) indicates that cytotoxic T-lymphocytes along with macrophages are actively involved in the destruction of platelets in patients resistant to the surgical treatment of the disease. Morphometric criteria for unfavorable prognosis of immune thrombocytopenia after splenectomy were determined.


Author(s):  
Jack Arnold ◽  
Kevin Winthrop ◽  
Paul Emery

Abstract The coronavirus disease 2019 (COVID-19) vaccination will be the largest vaccination programme in the history of the NHS. Patients on immunosuppressive therapy will be among the earliest to be vaccinated. Some evidence indicates immunosuppressive therapy inhibits humoral response to the influenza, pneumococcal and hepatitis B vaccines. The degree to which this will translate to impaired COVID-19 vaccine responses is unclear. Other evidence suggests withholding MTX for 2 weeks post-vaccination may improve responses. Rituximab has been shown to impair humoral responses for 6 months or longer post-administration. Decisions on withholding or interrupting immunosuppressive therapy around COVID-19 vaccination will need to be made prior to the availability of data on specific COVID-19 vaccine response in these patients. With this in mind, this article outlines the existing data on the effect of antirheumatic therapy on vaccine responses in patients with inflammatory arthritis and formulates a possible pragmatic management strategy for COVID-19 vaccination.


2020 ◽  
pp. 1-10
Author(s):  
Aicha El Allam ◽  
Sara El Fakihi ◽  
Hicham Tahoune ◽  
Karima Sahmoudi ◽  
Houria Bousserhane ◽  
...  

The number of circulating lymphocytes is altered in a number of diseases including either increase (lymphocytosis) or decrease (lymphocytopenia). Therefore, the assessment of total blood lymphocyte numbers and the relative distribution of lymphocyte subsets is a critical front-line tool in the clinical diagnosis of a number of diseases, including pediatric diseases and disorders. However, the interpretation of this data requires comparison of patient’s results to reliable reference values. Blood lymphocyte subpopulation numbers are also subject to genetic polymorphisms, immunogenic and environmental factors and vary greatly between populations. While the best practice reference values should be established within local representative populations of healthy subjects, to date, Caucasian reference values are used in Morocco due to the absence of indigenous reference values. Potential differences in blood lymphocyte subpopulation reference values between Caucasian versus Moroccan populations can adversely affect the diagnosis of pediatric and childhood diseases and disorders such as primary immunodeficiency (PID) in Morocco. OBJECTIVE: The aim of this study was to establish the age-stratified normal reference values of blood lymphocyte subsets for the pediatric Moroccan population. METHODS: We measured the concentration of lymphocyte subpopulations by flow cytometry from 83 Moroccan healthy subjects stratified into 5 age groups of 0–1, 1–2, 2–6, 6–12 and > 12–18 (adult). RESULTS: The absolute and relative amounts of the main lymphocyte subsets of T-cells, B cells and Natural Killer (NK) cells were measured and compared to previously described reference values from Cameroonian, Turkish, American and Dutch populations. Additionally, we also observed an age-related decline in the absolute population sizes of lymphocyte subsets within our study group. Relative proportions of CD3+CD4+ helper T lymphocytes decreased with increasing age and by 12 years-adult age, both proportions of CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, as well as CD3-CD19+ B lymphocytes were also decreased. Finally, we compared the median values and range of our Moroccan study group with that of published results from Cameroon, Turkey, USA and Netherlands and observed significant differences in median and mean values of absolute number and relative proportions of lymphocyte subsets especially at 0–1 years and 1–2 years age groups. Above age 12 years, the Moroccan values were lower. For NK cells, the Moroccan values are also lower. CONCLUSIONS: The results of this study have a significant impact in improving the threshold values of the references intervals routinely used in the diagnosis of paediatric diseases such as PIDs or mother-to-child transmitted HIV within the Moroccan population.


2021 ◽  
Vol 10 (8) ◽  
pp. 1771
Author(s):  
Violetta Opoka-Winiarska ◽  
Ewelina Grywalska ◽  
Izabela Korona-Glowniak ◽  
Katarzyna Matuska ◽  
Anna Malm ◽  
...  

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients’ humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dehua Lu ◽  
Yanpu Wang ◽  
Ting Zhang ◽  
Feng Wang ◽  
Kui Li ◽  
...  

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 492
Author(s):  
Yunhwa Kim ◽  
Ji-Young Hwang ◽  
Kyung-Min Lee ◽  
Eunsil Lee ◽  
Hosun Park

The prevalence of varicella is especially high among children in the age group of 4–6 years in South Korea, regardless of vaccination. We investigated the immune status of healthy children enrolled in day-care centers and compared pre- and post-vaccination immunity. Antibody titers were measured using a glycoprotein enzyme-linked immunosorbent assay (gpEIA) kit, and the seroconversion rate was assessed using a fluorescent antibody to membrane antigen (FAMA) test. Among 541 vaccinated children, 109 (20.1%) had breakthrough varicella. However, 13 (72.2%) of the 18 unvaccinated children had a history of varicella. The gpEIA geometric mean titers (GMTs) of pre- and 5 weeks post-vaccination in 1-year-old children were 14.7 and 72 mIU/mL, respectively, and the FAMA seroconversion rate was 91.1%. The gpEIA GMTs of 2-, 3-, 4-, 5-, and 6-year-old children were 104.1, 133.8, 223.5, 364.1, and 353.0 mIU/mL, respectively. Even though the gpEIA GMT increased with age, the pattern of gpEIA titer distribution in 4- to 6-year-old vaccinees without varicella history represented both waning immunity and natural boosting immunity. These results suggest that some vaccinees are vulnerable to varicella infection. Therefore, it is necessary to consider a two-dose varicella vaccine regimen in South Korea.


Sign in / Sign up

Export Citation Format

Share Document