Total Lymphocyte Levels Research Articles

DIPG-36. DRD2 ANTAGONISM RESCUES IMMUNE-TUMOR SURVEILLANCE, WARMING THE TUMOR IMMUNE MICROENVIRONMENT OF DIFFUSE MIDLINE GLIOMA MODELS

Abstract BACKGROUND Less than 10% of patients with diffuse midline glioma (DMG) survive 2-years post-diagnosis, with no approved treatments other than palliative radiotherapy. Immune-checkpoint inhibition has failed in the clinic, likely due to a lack of tumor infiltrating lymphocytes (TILs) and limited/no expression of immune checkpoint proteins or proinflammatory cytokines in the tumor immune microenvironment (TIME). Similarly, glioblastoma patients suffer from a ‘cold’ TIME, linked to the sequestration of T cells in the bone marrow (BM) through β-arrestin-induced internalization of S1PR1. β-arrestin is activated by Dopamine receptors (DRD2); therefore, we hypothesized that systemic DRD2 antagonism using the antagonist ONC201, might reverse lymphopenia, increasing TIL populations. METHODS Flow cytometry analysis was performed on bloods from DMG patients at diagnosis. Circulating immune cells and BM from the immunocompetent PPK model +/-ONC201 and tumor-naïve mice were analyzed by a hematology analyzer and flow cytometry. Immunocompromised SU-DIPG-VI and HSJD-DIPG-007 and immunocompetent XFM murine models were treated +/-ONC201 and tumors analyzed by immunoblotting, immunohistochemistry, and flow cytometry. scRNAseq and scATACseq analysis was performed on tumors from immunocompetent PPK models +/-ONC201. RESULTS DMG patients displayed low levels of total lymphocytes, including CD4+, CD8+ and NK subsets (n=9). Similarly, DMG-bearing mice displayed lower levels of lymphocytes (CD45+, CD4+, CD8+ subsets, n=3) compared to sham-engrafted mice. ONC201 treated mice showed lymphocyte levels comparative to sham-engrafted mice, reversing tumor-induced lymphopenia. A significant increase of T cells expressing S1PR1+ was seen in the BM following ONC201. Tumor immune cell infiltration following ONC201 was confirmed in both immunocompromised and immunocompetent models. Multiomics analysis identified ONC201 to promote pro-inflammatory polarization of microglia/macrophages (MHC II and CD86) and increase expression of immune checkpoints (VISTA and PD-L1). CONCLUSIONS DMG patients suffer from low peripheral lymphocytes, likely contributing to cold TIME. ONC201 reversed tumor-induced lymphopenia, promoting TIL recruitment within the tumor, warming the TIME.

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis-A Real-World Scenario.

Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary.

HUBUNGAN KADAR LEUKOSIT DAN TOTAL LIMFOSIT DENGAN KELAINAN PARU PADA PASIEN COVID-19

Before the administration of vaccine, the impact of COVID-19 infection on the lungs was significant, affecting the prognosis and quality of life of patients. Identifying the severity of lung damage requires markers to identify the patient's condition early on, preventing further damage and abnormalities that may arise, especially in the lungs. The aim of this study is to reduce the occurrence of post-COVID-19 lung fibrosis by assessing the relationship between leukocyte and total lymphocyte levels and lung abnormalities in COVID-19 patients. The research method used is observational analytics with a cross-sectional design. The data used are secondary data, consisting of medical records of 112 COVID-19 patients as research subjects. The variables studied are leukocyte and total lymphocyte levels according to laboratory result, and documented lung abnormalities in medical records. The data is then analyzed using the Chi-square test with a significance level of p<0.05. Lung abnormalities, particularly pneumonia, are dominated by increased leukocyte levels in 62 individuals (91.2%) and decreased total lymphocyte levels in 63 individuals (94.1%). There is a significant association between leukocyte levels with lung abnormalities (p = 0.021), and total lymphocytes with lung abnormalities (p = 0.001).

Pulmonary Sarcoidosis and Immune Dysregulation: A Pilot Study on Possible Correlation.

Sarcoidosis is a systemic inflammatory disease characterized by an altered inflammatory response. The aim of this study was to evaluate whether immune system alterations detected by lymphocyte typing in peripheral blood correlate with the severity of sarcoidosis, calculated according to two separate severity scores proposed by Wasfi in 2006 and Hamzeh in 2010. Eighty-one patients were recruited, and clinical data and laboratory tests at the time of diagnosis were obtained in order to assess the severity index score and investigate any statistically significant correlation with the cytofluorimetry data. Our data demonstrated that none of the two scores show an association with the level of total lymphocytes or lymphocyte subclasses. First of all, the sample taken into consideration is small. The assessment was performed only at disease onset and not during the disease. Furthermore, the severity scores do not take into account disease activity (measured by PET/CT or gallium scintigraphy). Lymphocyte subpopulation values at the time of diagnosis do not appear to correlate with disease severity at onset.

Phenotypical evaluation of lymphocytes and monocytes in patients with type 2 diabetes mellitus in Saudi Arabia.

To evaluate the levels of total lymphocytes, B-lymphocytes (CD19+), T-lymphocytes (CD3+), natural killer (NK) cells (CD3-/CD56+), and monocyte subsets in type 2 diabetes mellitus (T2DM) patients in Saudi Arabia. In addition, this study aimed to evaluate whether B- and T-lymphocyte subsets are frequently altered in patients with T2DM. A case-control study included 95 participants recruited in the study: 62 patients with T2DM and 33 healthy individuals. All the patients were admitted to the Diabetic Centre in Taif, Saudi Arabia. Blood samples were collected between April and August 2022. The hemoglobin A1c (HbA1c) level was evaluated in all patients. Flow cytometry was used to measure the expression of B-lymphocyte, T-lymphocyte, NK cells, and monocyte markers. The unpaired t-test was carried out to evaluate the differences in these markers between T2DM patients and healthy individuals. Patients with T2DM were associated with a lower percentage of total lymphocytes, higher percentage of B-lymphocytes, naive, and memory B subsets. In addition, patients with T2DM showed lower percentage of total T-lymphocytes (CD3+) and CD4T-cells, but higher CD8T-cell expression. Also, the NK-cell level was reduced in patients with T2DM, and the levels of monocyte subsets were altered. These data suggested that levels of lymphocytes and monocytes are impaired in T2DM patients, and this might be associated with the higher risk of infections observed in these patients.

Effects of syphilis infection among HIV-1-positive individuals on suppressive antiretroviral therapy

IntroductionIncident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear.MethodsPWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared.ResultsBetween 2005 and 2020, 288 syphilis episodes from 180 individuals wereidentified; 287 episodes were related to male, with a median age of 41 atdiagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1suppression were statistically unchanged across the time-points (97% pre-syphilis,98% during syphilis, and 99% post-treatment).Total lymphocyte, CD4+ and CD8+ T-cell levels decreased duringincident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRLtitre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell(p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratiowas associated with increases in CD8+ T-cell (p=0.001) and total lymphocytelevels (p=0.046) during syphilis. Syphilis re-infection was associated with anincrease in total lymphocyte level (p=0.037). In the multivariable analysis,only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis.ConclusionsAmong virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-celllevels declined duringincident syphilis but rebounded post-treatment. The status of plasma HIV suppressionwas unaffectedby syphilis.

Supplementary Role of Immunological Indicators in the Diagnosis and Prognosis of Pneumocystis Pneumonia in Non-HIV Immunocompromised Patients.

BackgroundPneumocystis pneumonia (PCP) has a high mortality in HIV-negative immunocompromised patients. The occurrence and development of PCP are believed to be correlated with the level of lymphocytes and their subsets. The aim of this study was to determine if the levels of lymphocyte subpopulations and immunoglobulin are associated with PCP.MethodsA total of 74 immunocompromised patients were enrolled in this single-center cohort study. Diagnosis of PCP was based on the relevant pulmonary symptoms and radiological imaging, and the detection of Pneumocystis jirovecii in BAL fluid or biopsy tissue by metagenomic next-generation sequencing (mNGS). All patients were divided into two groups (PCP group and non-PCP group) and the patients in PCP group were then divided into two groupsbased on the outcome of the disease during the hospitalization.ResultsWe observed a significant lower level of IgG (p=0.000) and B lymphocyte counts (p=0.017) in the PCP group comparing to that in the non-PCP group. CD4+ T cell counts, as well as the ratio of CD4+/CD8+ T cells in circulation and BAL fluid were also lower in the PCP group comparing to those in the non-PCP group. Lactate dehydrogenase (LDH) in the PCP group was significantly higher than that in the non-PCP group (p=0.029). In the PCP group, a lower level of total lymphocytes (p=0.004), T cells (p=0.001), CD4+ cells (p=0.001), and CD8+ cells (p=0.007), as well as the proportion of lymphocytes in BAL fluid (p=0.000) were found in deceased patients comparing to those in the survived group.ConclusionOur study revealed an important role of humoral immunity in the infection of Pneumocystis jirovecii. The level of B cells and IgG could be used as a supplement to predict the occurrence of PCP. The level of CD4+ and CD8+ lymphocytes was significantly correlated with the outcome of PCP.

An association between immune status and chest CT scores in COVID-19 patients.

BackgroundThe characteristic features of the immune responses of COVID‐19 patients and how they reflect lung involvement have not been clearly elucidated.AimThe aim of this study was to examine the immune status and the correlations thereof with chest CT scores and lung involvement of patients with COVID‐19.MethodsIn this retrospective and single‐center study, 72 patients with laboratory‐confirmed COVID‐19 were recruited. The counts of peripheral lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells and CD16+ 56+ NK cells) and those of serum immunoglobulins (IgA, IgG, IgM) were measured and their associations with chest CT scores analysed.ResultsThe proportions of lymphopenia in patients with extensive lung involvement were twice that in the general study population. In the severe disease group, the levels of total lymphocytes, T cells, B cells, NK cells; and serum IgA levels, were significantly lower than in the mild disease group (all P < .05). We found that the numbers of lymphocyte subsets and the IgA level negatively correlated with the chest CT scores. On multivariate regression analysis, pretreatment decreases in total lymphocytes, CD3+ T cells, CD4+ T cells, and CD19+ B cells, and serum IgA levels, were independent predictors of severe lung involvement.ConclusionsThe cell numbers of peripheral lymphocyte subsets and the serum IgA level were negatively correlated with the chest CT scores in COVID‐19 patients. These parameters tended to independently predict severe lung involvement in such patients.

Letermovir Administration to Prevent Cytomegalovirus Reactivation Is the Potential Risk of Chronic Graft-Versus-Host Disease in Patients Who Received Haploidentical Stem-Cell Transplantation With Post-Transplant Cyclophosphamide.

The prevention of chronic graft-versus-host disease (cGVHD) is important for recipients of hematopoietic stem-cell transplantation (HSCT). As one of the etiologies, the relationship between early T-cell recovery and subsequent cGVHD development has been the focus of attention. Recently, letermovir (LTV) was approved for preventing cytomegalovirus (CMV) reactivation in the early transplantation phase. Although CMV affects the immune reconstitution after HSCT, the impacts of LTV to prevent CMV reactivation on early T-cell recovery and cGVHD have not been fully investigated. We aimed to identify early T-cell recovery under LTV at day 30 in 15 and 33 recipients from matched related donors (MRDs) and haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo), respectively. Early increases in the levels of total lymphocytes and HLA-DR+ activated T-cells at day 30 were observed under CMV prophylaxis by LTV only in PTCy-haplo recipients and not in MRD recipients. Moreover, PTCy-haplo recipients with LTV showed a significantly higher incidence of cGVHD, but not acute GVHD. Our observations suggest that an early increase in the levels of HLA-DR+ activated T-cells may be implicated in the development of cGVHD in patients treated with PTCy who received LTV. Further studies are warranted to validate our results and elucidate the detailed mechanisms of our new insights.

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19

BackgroundThe lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis.MethodsA total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected.ResultsOn admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells.ConclusionsA sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Circulating Cytokines and Lymphocyte Subsets in Patients Who Have Recovered from COVID-19.

To investigate the immune status of people who previously had COVID-19 infections, we recruited two-week postrecovery patients and analyzed circulating cytokine and lymphocyte subsets. We measured levels of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells and the serum concentrations of interleukin- (IL-) 1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most postrecovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8+ T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells (51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%), and IL-17 (97.06%). Compared to healthy controls, two-week postrecovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17. Among postrecovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells were positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, postrecovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system gradually recovers following COVID-19 infection; however, the sustained hyperinflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

The effect of vitamin-d levels on prognosis of elderly patients treated in intensive care unit

Giriş ve Amaç: Dünyada yaşlı nüfusun %50-60’ında vitamin D eksikliği vardır. Kritik hastalarda ise vitamin D eksikliğinin (25(OH)D&amp;lt;20ng/ml) prevalansı %70’i aşmaktadır. Bu çalışmada Yoğun Bakım Ünitesi(YBÜ)’nde takip ve tedavi edilen 65 yaş üstü; vitamin D verilen ve verilmeyen hastaların prognoz açısından karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Kasım 2014-Nisan 2015 tarihleri arası hastanemiz YBÜ ’de takip ve tedavi edilen hastaların kayıtları geriye dönük olarak incelendi. Enteral beslenen ve vitamin D desteği alan 20 hasta (Grup D), enteral beslenen ancak vitamin D desteği almayan 20 hasta (Grup K) arasında yoğun bakıma kabul sırasında(T1), 7.(T2) ve 15.(T3) günlerde ölçülen vitamin D, albümin, prealbumin, total lenfosit, CRP düzeyleri ve triceps kas kalınlığı açısından fark olup olmadığı değerlendirildi. Bulgular: İki grup demografik veriler açısından benzerdi. Grup D ile Grup K arasında T1,T2 ve T3 zamanlarında vitamin D düzeyleri, albümin- prealbümin düzeyleri, enfeksiyon oranları, mekanik ventilasyon süreleri, yoğun bakım yatış günü ve mortalite açısından istatistiksel olarak anlamlı bir fark saptanmazken T1 ve T2 zamanında total lenfosit(TLS) düzeyleri(p&amp;lt;0,05) vitamin D grubunda istatistiksel olarak anlamlı yüksek idi. Hastaların sadece T3 zamanında vitamin D ve diğer değişkenler ele alındığında ise APACHE II değerleri, MV gün, T3 albümin, T3 prealbümin ve T3 total proteinle istatistiki olarak anlamlı ilişki gözlendi. Sonuç: Çalışmamızda vitamin D verilen grupla verilmeyen grup arasında bazı değişkenlerde anlamlı fark gözlenmesi, prospektif ve daha fazla sayıda hasta ile yapılacak çalışmalar açısından yol gösterici olacağını düşünmekteyiz.

Non-intubated anesthesia in patients undergoingvideo-assisted thoracoscopic surgery: Asystematic reviewand meta-analysis.

IntroductionNon-intubated anesthesia (NIA) has been proposed for video-assisted thoracoscopic surgery (VATS), although how the benefit-to-risk of NIA compares to that of intubated general anesthesia (IGA) for certain types of patients remains unclear. Therefore, the aim of the present meta-analysis was to understand whether NIA or IGA may be more beneficial for patients undergoing VATS.MethodsA systematic search of Cochrane Library, Pubmed and Embase databases from 1968 to April 2019 was performed using predefined criteria. Studies comparing the effects of NIA or IGA for adult VATS patients were considered. The primary outcome measure was hospital stay. Pooled data were meta-analyzed using a random-effects model to determine the standard mean difference (SMD) with 95% confidence intervals (CI).Results and discussionTwenty-eight studies with 2929 patients were included. The median age of participants was 56.8 years (range 21.9–76.4) and 1802 (61.5%) were male. Compared to IGA, NIA was associated with shorter hospital stay (SMD -0.57 days, 95%CI -0.78 to -0.36), lower estimated cost for hospitalization (SMD -2.83 US, 95% CI -4.33 to -1.34), shorter chest tube duration (SMD -0.32 days, 95% CI -0.47 to -0.17), and shorter postoperative fasting time (SMD, -2.76 days; 95% CI -2.98 to -2.54). NIA patients showed higher levels of total lymphocytes and natural killer cells and higher T helper/T suppressor cell ratio, but lower levels of interleukin (IL)-6, IL-8 and C-reactive protein (CRP). Moreover, NIA patients showed lower levels of fibrinogen, cortisol, procalcitonin and epinephrine.ConclusionsNIA enhances the recovery from VATS through attenuation of stress and inflammatory responses and stimulation of cellular immune function.

Relationship of the Changes of Peripheral Blood Immuno-Cell Subsets with the Prognosis of B Cell Lymphoma Patients

To investigate the relationship of T lymphocyte subsets, B lymphocytes and NK cells with the genesis, progression and prognosis of B cell lymphoma. The levels of T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood of healthy control group and B cell lymphoma group were detected by flow cytometry (FCM). The clinical data were collected, and the relationship of these immune indexes with the general conditions, laboratory indexes, curative effect and prognosis were analyzed. Forty-four patients entolled in this study including 24 male and 20 females with the median age of 57 years old (17-82 years), all the patients were the first visit to our hospital and diagnosed. The total counts of lymphocytes, T, B and NK cells in the peripheral blood of patients with the first treatment of B-cell lymphoma were significantly lower than those in healthy controls, and the ratio of CD3+HLA-DR+ activated T cells was significantly higher than that of healthy controls (<0.05). In the newly diagnosed patients, the levels of total lymphocytes, total T cells, total B cells, CD4+ cells and NK cells in peripheral blood of patients with complete remission (CR) were higher than those in patients without complete remission ［partial remission (PR) and disease progression（PD）］ (<0.01, <0.01, <0.05, <0.01, <0.05, respectively). The logistic regression analysis showed that NK cells, FAC-1（FAC-1 is a component factor for linear regression of total lymphocytes, total T cells, and total B cells）, the ECOG score and β2-microglobulin level were significantly different between CR group and PR+SD group (<0.05, <0.01, <0.05, <0.01, respectively), among which ECOG score and β2-microglobulin were independent risk factor respectively for the prognosis of patients. The NK cells and FAC-1 were the protective factors for the prognosis of patients. The survival analysis performed according to the NK cell level of patients at initial diagnosis, the Kaplan-Meier survival curve found that the overall survival (OS) of the 2 groups was significantly different (<0.01), the survial rate in patients with NK cell absolute count> 61.5 /μl was higher than that in patients with low level of NK cells. The level of total lymphocytes, total T cells, total B cells, NK cells and advanced activated T cells in the patients with B cell lymphoma were significantly different from those in normal subjects. Total count of lymphocytes, T cells, B cells, CD4+ cells and NK cells in peripheral blood are important prognostic indicators for BCL. The ECOG score and β2-microglobulin level are independent risk factors for prognosis. The NK cell level and FAC-1 are independent protective factors for the prognosis of B cell lymphoma.

In neonates with vitamin D deficiency, low lymphocyte activation markers are risk factors for infection

ABSTRACTBackground: Vitamin D has regulatory effects on different cells of the immune system and low levels are associated with several immune-mediated diseases.Aim: To investigate the association between neonatal 25-hydroxy vitamin D (25-OHD) level and the expression of lymphocyte activation markers (HLA-DR, CD69, CD25, CD45RA) on T-lymphocyte subpopulations and its impact in neonatal infection.Methods: 25-OHD level was measured in the cord blood of 56 neonates and their mothers using an enzyme immune-assay method. Based on the 25-OHD level, infants were categorised into four groups: severe deficiency (n = 7), moderate deficiency (n = 21), mild deficiency (n = 15) and normal 25-OHD level (n = 13). Mothers were classified into deficient (n = 18), insufficient (n = 21) and normal levels (n = 17). T-lymphocyte subpopulations and lymphocyte activation markers were investigated using flow cytometry.Results: There was a positive correlation between maternal and cord blood 25-OHD levels (r = 0.503, p = 0.001). The group with severe 25-OHD deficiency had the significantly lowest level of total lymphocytes, CD3+ T lymphocytes, CD4+ T-helper and CD8+ T-cytotoxic lymphocytes and CD4+CD45RA+ naïve T-cells compared with the other groups. The frequencies of CD8+CD25+, CD4+CD25+ and CD4+HLA-DR+ activated T-lymphocytes were significantly lower in the severe, moderate and mild deficiency groups than in the normal group. Seven of 43 (16.27%) infants with 25-OHD deficiency were admitted with sepsis to the neonatal intensive care unit and there were no cases of sepsis in the normal 25-OHD group.Conclusion: Vitamin D deficiency is associated with a reduction of lymphocyte subsets and altered T-lymphocyte activation which are considered to be risk factors for neonatal infection.

Total Blood Lymphocyte Count Alteration During and after Pregnancy

Objective: To investigate the impact of gestational changes on blood lymphocyte count in healthy pregnancies. Study Design: This retrospective study is consisted of 108 consecutive normal pregnancies who delivered at our department in December 2015. High-risk pregnancies with poor neonatal outcome and pregnancies with maternal disorders which may affect lymphocyte counts were excluded from the study. “Complete blood count” results of the patients were obtained from the computerized data base system of Hacettepe University Hospital. Blood samples of patients which were withdrawn a) prior to pregnancy (1-6 months before getting pregnant), b) during pregnancy (11-14th gestational weeks) and c) post-partum first day were used in this study.Results: The mean blood lymphocyte count was 2049.07 (±758.69) in patients before their pregnancies. The mean lymphocyte count decreased to 1850.93 and 1625 during pregnancy and after delivery respectively. A statistically significant decrease was found between three periods (before, during, and postpartum 1st day) (p:0.003).Conclusion: We have shown a significant decrease in total lymphocyte levels during pregnancy, consistent with the data presented in the literature. Pregnancy and related hormones have a negative impact on total blood lymphocyte level.

Nutritional Status and Fatigue in Women Cancer Patients Receiving Chemotherapy*

Purpose: This study aimed to evaluate nutritional status and fatigue, and to identify the relationship between nutritional status and fatigue in gynecological cancer patients receiving chemotherapy. Methods: Participants were 106 outpatients who had uterine, ovary, or breast cancer and a descriptive cross-sectional design was used. Nutritional indicators including biochemical and anthropometric measures, the Subjective Global Assessment (SGA) scale, and the Piper's Revised Fatigue Scale were completed. Results: About thirty-nine percent of the patients were malnourished based on the SGA. Serum hemoglobin and total lymphocyte levels were less than the normal ranges, although anthropometrics were normal. The women experienced moderate fatigue with a mean score of . Nutritional status was significantly different by age, education, employment status, and monthly income. The women also had different nutritional status and fatigue depending on the type of cancer and chemotherapy. Fatigue was significantly related to SGA scores, serum hemoglobin, triceps skinfold thickness and mid-arm muscle circumference. Conclusion: The results of this study highlight an urgent need to provide adequate nutritional support and fatigue management with individualized strategies for gynecological cancer patients on chemotherapy.

Intensive Phase of Therapy of Tuberculosis and HIV Co-infection: CD4, CD8, and Certain Hematological Finding Amongst Patients in Yaounde Cameroon

Tuberculosis (TB) is an infectious disease which could cause depressive phenomena like those observed in Human Immunodeficiency Virus (HIV). Our study aimed at evaluating the changes of T-cells and certain blood parameters during intensive phase of TB treatment. In this prospective cohort, 140 consenting tuberculosis patients were enrolled. 5ml of blood was collected at baseline (M0), after one month (M1) and after two months (M2). Enumeration of CD4 cells, CD8 cells, and hematological parameters were done following standard protocols.The 118 participants comprised 63 (53.4%) TB/HIV negative patients (group 1) and 55 (46.6%) TB/HIV positive patients (group 2). At M0, blood levels of CD4, hemoglobin, total lymphocytes and platelets in group 2 were significantly lower than those of group 1 with p values of 0.001, 0.002, 0.018 and 0.032 respectively. CD8 level was significantly low in group 1 as compared to group 2 (p value: 0.38). Monocytes were low in both groups with no significant difference (p value: 0.097). At M2, there was a significant increase in the levels of CD4, CD8, monocytes, and hemoglobin as compared to M0. There was no significant change on level of total lymphocytes and platelets. In group 2: At M2, there was a significant increase in the levels of CD4, monocytes, hemoglobin, and platelets, and no statistically significant change on levels of CD8 cells and total lymphocytes. TB infection may result in lymphopenia, monopenia, and anemia, while co-infection with HIV may add thrombopenia to the mentioned disorders.

Streptavidin: a novel immunostimulant for the selection and delivery of autologous and syngeneic tumor vaccines.

Induction of antitumor immunity using autologous tumor proteins is an attractive approach to cancer therapy. However, better methods and stimulants to present these autologous proteins back to the immune system are needed. Here, we identify streptavidin as a novel carrier protein and stimulant, and test the efficacy of both syngeneic (rat) and autologous vaccines (dogs) using streptavidin in combination with reduced soluble tumor proteins. Initial syngeneic vaccine studies in the 9L rat glioma model were used to optimize vaccine dose and selectivity. Cytokine and blood analysis was used to monitor the response. Rats receiving two vaccinations of syngeneic tumor vaccine demonstrated a statistically significant (P < 0.05) survival advantage compared with controls (adjuvant only). Notably, vaccination also led to remission rates of between 30% and 60% in the aggressive 9L glioma model. Antibodies to streptavidin were detected in the serum of vaccinated rats; however, antibody levels did not correlate with the response. The cytokine TNF-α was upregulated in vaccine-treated rats, whereas ICAM1 was downregulated. After engraftment, vaccinated rats maintained CD4(+), CD8(+) T cells, and total lymphocyte levels closer to normal baseline than those in the controls. Twenty-five dogs treated with autologous vaccine preparations using streptavidin as a stimulant showed no adverse reactions, irrespective of additional chemotherapy and other medications. In this study, we developed a novel method for producing syngeneic and autologous vaccines using streptavidin selectivity and immunogenicity. These vaccines show efficacy in the 9L glioma rat model. Safety was also demonstrated in canine patients presenting with cancer treated with autologous vaccine.

Experience in IVIg Therapy for Selected Women with Recurrent Reproductive Failure and NK Cell Expansion

Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells). Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation. By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P<0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P≤0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P≤0.0001). Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.