Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis

Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-β and higher systemic levels of neutrophil chemoattractants IL-8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients.

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Kinetics of Immune Reconstitution in Event-Free Patients: Establishing Reference Values for Immune Recovery of Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.5772.5772 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5772-5772

Author(s):

Xu-Ying Pei ◽

Yu Wang ◽

Lan-Ping Xu ◽

Xiao-Hui Zhang ◽

Xiang-Yu Zhao ◽

...

Keyword(s):

Reference Values ◽

Immune Reconstitution ◽

Immune Cell ◽

First Year ◽

Immune Recovery ◽

Hematopoietic Stem ◽

Post Transplant ◽

Cell Counts ◽

Healthy Donors ◽

Immune Cell Subsets

Abstract Background: Immune reconstitution (IR) is strongly associated with clinical outcomes after hematopoietic stem cell transplantation (HSCT). So far, there are no optimal reference values for recovered immune cell subsets after HSCT, and approaches to enhance post-transplant IR based on data from health donors have their limitations. Therefore, reference values need to be established for immune cell counts to monitor IR and identify high-risk patients needing aggressively supportive treatment. Methods: Between January 2011 and December 2013, 706 consecutive patients who received HLA-matched sibling transplantation (MSDT) or haploidentical transplantation (haplo-SCT) modality participated in this study. Finally a total of 144 patients who did not experience transplant complications such as poor graft function, grades II-IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, relapse or death in the first year after transplant were available for immune cell subset testing between day 30 and 365, and were analyzed in this study. To provide reference values that could be used for all recipients, the effects of recipient age, gender, and underlying disease on IR were investigated. In addition, 41 healthy donors underwent single time-point immune analysis, and the data were used as a normal control. Results: The 4-year probability of relapse, non-relapse mortality, leukemia-free survival, and overall survival was 5% (95% CI: 1%-9%), 1% (95% CI: 0%-2%), 95% (95% CI: 90%-99%), and 98% (95% CI: 96%-100%), respectively. Monocytes recovered rapidly and persisted at higher levels than normal during the first year after transplantation. The total CD3+ T cell counts were very low in the first 30 days but normalized by 90 days post-transplant. CD4+ helper T cells recovered very slowly and did not reach normal range by 1 year after transplantation. The absolute numbers of CD8+ T cells were higher after 90 days post-transplant compared to healthy donors. The recovery of CD19+ B cells was delayed during 1 year after transplantation. All immune cell subsets except monocytes recovered faster after MDST than haplo-SCT. By univariate and multivariate analysis, the haplo-SCT modality was confirmed to be associated with immune recovery. So the reference values for recovered immune cell subgroups were provided for MSDT and haplo-SCT, respectively. Conclusion: Our results suggest that patients with IR comparable to the reference values could have superior survival and the immune cells may not have to recover to healthy donor levels in the first year after transplantation. We emphasize that data from this recipient cohort should be understood as reference values for immune cell counts post-transplant for patients receiving HSCT. Acknowledgments: This work was supported, in part, by the National High Technology Research and Development Program of China (Program 863; Grant No. 2013AA020401) and the National Natural Science Foundation of China (Grant No. 81470342). We thank the faculty members who collected samples and analyzed the flow cytometry data. Disclosures No relevant conflicts of interest to declare.

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SARS-CoV-2-specific immune response in COVID-19 convalescent individuals

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00686-1 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Yunbao Pan ◽

Xianghu Jiang ◽

Liu Yang ◽

Liangjun Chen ◽

Xiaojiao Zeng ◽

...

Keyword(s):

Nk Cell ◽

Neutralizing Antibody ◽

Effective Vaccine ◽

Humoral And Cellular Immunity ◽

Cell Counts ◽

Healthy Donors ◽

Antigen Peptide ◽

Discharged Patients ◽

Ifn Γ

AbstractWe collected blood from coronavirus disease 2019 (COVID-19) convalescent individuals and investigated SARS-CoV-2-specific humoral and cellular immunity in these discharged patients. Follow-up analysis in a cohort of 171 patients at 4–11 months after the onset revealed high levels of IgG antibodies. A total of 78.1% (164/210) of the specimens tested positive for neutralizing antibody (NAb). SARS-CoV-2 antigen peptide pools-stimulated-IL-2 and -IFN-γ response can distinguish COVID-19 convalescent individuals from healthy donors. Interestingly, NAb survival was significantly affected by the antigen peptide pools-stimulated-IL-2 response, -IL-8 response, and -IFN-γ response. The antigen peptide pools-activated CD8+ T cell counts were correlated with NAb. The antigen peptide pools-activated natural killer (NK) cell counts in convalescent individuals were correlated with NAb and disease severity. Our data suggested that the development of NAb is associated with the activation of T cells and NK cells. Our work provides a basis for further analysis of the protective immunity to SARS-CoV-2 and for understanding the pathogenesis of COVID-19. It also has implications for the development of an effective vaccine for SARS-CoV-2 infection.

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Serum Levels of Interleukin-18 and sICAM-1 in Patients Affected by Breast Cancer: Preliminary Considerations

The International Journal of Biological Markers ◽

10.1177/172460080101600207 ◽

2001 ◽

Vol 16 (2) ◽

pp. 126-129 ◽

Cited By ~ 29

Author(s):

R.A. Merendino ◽

S. Gangemi ◽

A. Ruello ◽

A. Bene ◽

E. Losi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Immune Cell ◽

Metastatic Breast ◽

Serum Levels ◽

Intercellular Adhesion Molecule ◽

Interleukin 18 ◽

Intercellular Adhesion Molecule 1 ◽

Healthy Donors

Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper type 1 response, acts as an angiogenesis and tumor suppressor. Intercellular adhesion molecule-1 (ICAM-1) has a potential role in immunoregulation by mediating immune cell infiltration into the tissue. The aim of this study was to evaluate IL-18 and soluble (s) ICAM-1 serum levels in breast cancer (BCa) patients with liver (BCaM1h) or bone (BCaM1b) metastases compared to BCa patients without metastases (BCaM0) and healthy donors (HDs). Furthermore, since IL-18 enhances ICAM-1 expression, we investigated whether there was a direct correlation between sICAM-1 and IL-18 serum levels. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. The serum sICAM-1 levels in the three groups of cancer patients were significantly higher (p<0.05) than those of HDs. Serum IL-18 levels were significantly higher (p<0.05) in BCaM1h and BCaM1b patients compared to BCaM0 patients and HDs. sICAM-1 proved to be closely correlated with serum IL-18 levels in HDs, whereas a weaker correlation was found in BCaM1h, BCaM1b and BCaM0 patients. The defective correlation between sICAM-1 and IL-18 found in cancer patients may contribute to our understanding of the immunity upset occurring in cancer. Our data suggest that IL-18, irrespective of its biological activity, could represent a marker for metastatic breast cancer.

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Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System

International Journal of Molecular Sciences ◽

10.3390/ijms22115749 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5749

Author(s):

Genieve Ee Chia Yeo ◽

Min Hwei Ng ◽

Fazlina Binti Nordin ◽

Jia Xian Law

Keyword(s):

Immune System ◽

Immune Cell ◽

Serum Levels ◽

Health Sciences ◽

Present Knowledge ◽

Regenerative Therapy ◽

Geriatric Population ◽

Inflammatory State ◽

Promising Solution ◽

Pro Inflammatory Cytokines

Rapid growth of the geriatric population has been made possible with advancements in pharmaceutical and health sciences. Hence, age-associated diseases are becoming more common. Aging encompasses deterioration of the immune system, known as immunosenescence. Dysregulation of the immune cell production, differentiation, and functioning lead to a chronic subclinical inflammatory state termed inflammaging. The hallmarks of the aging immune system are decreased naïve cells, increased memory cells, and increased serum levels of pro-inflammatory cytokines. Mesenchymal stem cell (MSC) transplantation is a promising solution to halt immunosenescence as the cells have excellent immunomodulatory functions and low immunogenicity. This review compiles the present knowledge of the causes and changes of the aging immune system and the potential of MSC transplantation as a regenerative therapy for immunosenescence.

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Circulating Interleukin-6 (but Not Other Immune Mediators) Associates with Criteria for Fried’s Frailty among Very Old Adults

Journal of Aging Research ◽

10.1155/2020/6831791 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Gilberto Santos Morais Junior ◽

Diego Ignacio Valenzuela Perez ◽

Audrey Cecília Tonet-Furioso ◽

Lucy Gomes ◽

Karla Helena Coelho Vilaça ◽

...

Keyword(s):

Grip Strength ◽

Serum Levels ◽

Total Serum ◽

Strong Negative Correlation ◽

Old Patients ◽

Walk Speed ◽

Very Old ◽

Old Adults ◽

Immune Mediators ◽

Inflammatory State

Background and Aim. Frailty is a geriatric condition resulting from physiological changes covering the musculoskeletal, immune, and neuroendocrine systems, leading to a greater inflammatory state. The present research aimed to investigate the association of components of Fried’s frailty (as well as of the phenotype as a whole) with total serum levels of a panel of inflammatory mediators. Methods. One hundred and sixty-one very old patients (aged ≥80 years) devoid of cognitive decline were eligible for analyses. Clinical and biochemical data along with physical and cognitive assessments encompassing dual-energy X-ray scans and hand dynamometry were adopted to investigate frailty criteria, while circulating immune mediators (IFNγ, IL-2, IL-4, IL-6, IL-10, and TNFα) were assessed using high-throughput flow cytometry. Results. Preliminarily, IL-6 correlated positively with waist-to-hip ratio and C-reactive protein and negatively with glycemia. In analyses controlled for these factors, serum levels of IL-6 were comparatively augmented among the very old participants with reduced grip strength (OR = 3.299; 95% CI 1.08–6.09; p = 0.032 ) and among those with slow walk speed (OR = 2.460; 95% CI 1.16–7.05; p = 0.022 ). Conclusions. Our study shows a strong negative correlation of IL-6 levels with Fried’s frailty components of grip strength and walk speed in very old adults, regardless of confounding factors.

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Amino Acid and Acylcarnitine Levels in Chronic Patients with Schizophrenia: A Preliminary Study

Metabolites ◽

10.3390/metabo11010034 ◽

2021 ◽

Vol 11 (1) ◽

pp. 34

Author(s):

Irina A. Mednova ◽

Alexander A. Chernonosov ◽

Marat F. Kasakin ◽

Elena G. Kornetova ◽

Arkadiy V. Semke ◽

...

Keyword(s):

Oxidative Stress ◽

Amino Acids ◽

Amino Acid ◽

Chronic Schizophrenia ◽

Integrated Approach ◽

Serum Levels ◽

Tandem Mass ◽

Chronic Patients ◽

Healthy Donors ◽

Preliminary Study

Amino acids and acylcarnitines play an important role as substrates and intermediate products in most of pathways involved in schizophrenia development such as mitochondrial dysfunction, inflammation, lipid oxidation, DNA damage, oxidative stress, and apoptosis. It seems relevant to use an integrated approach with ‘omics’ technology to study their contribution. The aim of our study was to investigate serum amino acid and acylcarnitine levels in antipsychotics-treated patients with chronic schizophrenia compared with healthy donors. We measured serum levels of 15 amino acids and 30 acylcarnitines in 37 patients with schizophrenia and 36 healthy donors by means of tandem mass spectrometry. In summary, patients with chronic schizophrenia had an altered concentration of a few amino acids and acylcarnitines in comparison to the healthy probands. Further research is needed to assess and understand the identified changes.

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Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles

Processes ◽

10.3390/pr7050301 ◽

2019 ◽

Vol 7 (5) ◽

pp. 301

Author(s):

Muying Wang ◽

Satoshi Fukuyama ◽

Yoshihiro Kawaoka ◽

Jason E. Shoemaker

Keyword(s):

Gene Expression ◽

Gene Expression Data ◽

Immune Cell ◽

Mean Squared Error ◽

Expression Profiles ◽

Statistical Tests ◽

Critical Factor ◽

Expression Data ◽

Cell Dynamics ◽

Cell Counts

Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R 2 ) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests.

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Impact of Weight on Immune Cell Counts among HIV-Infected Persons

Clinical and Vaccine Immunology ◽

10.1128/cvi.00020-11 ◽

2011 ◽

Vol 18 (6) ◽

pp. 940-946 ◽

Cited By ~ 23

Author(s):

Nancy F. Crum-Cianflone ◽

Mollie Roediger ◽

Lynn E. Eberly ◽

Anuradha Ganesan ◽

Amy Weintrob ◽

...

Keyword(s):

Highly Active Antiretroviral Therapy ◽

Immune Cell ◽

White Cell Count ◽

Normal Weight ◽

Longitudinal Models ◽

Hiv Diagnosis ◽

Highly Active ◽

Cell Counts ◽

Few Data ◽

Cd4 Percentage

ABSTRACTPrior studies have shown that weight may impact immune cell counts. However, few data exist about the relationship of weight and immune cell counts among HIV-infected patients. We examined documented HIV seroconverters (mean window, 15.7 months) in a prospective U.S. Military HIV Natural History Study (1 January 1986 to 20 January 2010). We estimated the association of the time-updated body mass index (BMI) category with changes in immune cell counts from HIV diagnosis across time (mean follow-up of 5.1 years) using multiply adjusted longitudinal linear mixed-effects models. Of 1,097 HIV seroconverters, 448 (41%) were overweight and 93 (8%) were obese at HIV diagnosis. Immune cell counts at HIV diagnosis did not significantly differ by BMI category. In the longitudinal models for those diagnosed before the advent of the highly active antiretroviral therapy (HAART) era, mean postdiagnosis decreases in the white cell count, total lymphocyte count, CD4 count, CD4 percentage, and CD4/CD8 ratio were less as the BMI category increased (all withPvalues of <0.05). Among HIV seroconverters diagnosed in the HAART era, obese compared to normal-weight patients had significantly smaller increases in CD4 counts, CD4 percentages, and the CD4/CD8 ratio (all withPvalues of <0.05). Similar findings were also noted among underweight versus normal-weight patients. In conclusion, although BMI was not associated with immune cell levels at the time of HIV diagnosis, weight appears to affect immune cells counts over the course of infection. In the HAART era, being either underweight or obese was associated with smaller increases in several important immune cell levels, including the CD4/CD8 ratio.

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Interferon beta-1a induces expression of brain-derived neurotrophic factor in human T lymphocytes in vitro and not in vivo

Future Neurology ◽

10.2217/fnl-2019-0018 ◽

2020 ◽

Vol 15 (1) ◽

pp. FNL38 ◽

Cited By ~ 1

Author(s):

Zarlascht Karmand ◽

Hans-Peter Hartung ◽

Oliver Neuhaus

Keyword(s):

T Cell ◽

Neurotrophic Factor ◽

Serum Levels ◽

Brain Derived Neurotrophic Factor ◽

Peripheral Blood Lymphocytes ◽

T Cell Proliferation ◽

Bdnf Expression ◽

Healthy Donors

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

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